SARS-CoV-2 and COVID-19 (22)

Dr Zoë Hyde (epidemiologist and biostatistician) @DrZoeHyde | 6:08 AM · Jun 5, 2021
https://twitter.com/DrZoeHyde/status/1401118714641092610
https://threadreaderapp.com/thread/1401118714641092610.html

The latest data from the UK’s Office for National Statistics show that over 1 million people in Great Britain are estimated to be living with long COVID.
Nearly 400 thousand of these have been living with long COVID for at least one year.

https://ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsan...
Image-table # cases by UK regions ( https://twitter.com/DrZoeHyde/status/1401118714641092610/photo/1 )
Image-duration March-May 2021 ( https://twitter.com/DrZoeHyde/status/1401118714641092610/photo/2 )

A thread...

Eric Topol @EricTopol | 11:15 AM · Jun 6, 2021:
With a strong vaccination campaign, the United States was able to reduce the B.1.1.7 (alpha) variant's toll to a bump in cases.
What might happen with B.1.617.2 (delta) which is ~50% more transmissible, and more evasive to our immune response? /1
Image-graph ( https://twitter.com/EricTopol/status/1401558311627943945/photo/1 )

It will be hitting us with a far less case burden, as we approach containment for the 1st time.
But still much vulnerability d/t half the population unvaccinated and ~40% fully vaccinated
2 doses appear to be needed to get to high ~90% effectiveness /2

We'll likely see a bump in cases and adverse outcomes (magnitude uncertain) largely among unvaccinated, and a challenge to get to containment in a fully reopened country, prolonging the pandemic here /3
Graphic adapted from @tomhcalver thetimes
Image ( https://twitter.com/EricTopol/status/1401558318506602498/photo/1 )

This could be thwarted if we can get vaccinations way up again. It'll be weeks before delta, the most formidable variant we've seen, becomes dominant
We're extremely fortunate to have a highly effective & safe vaccine to mitigate its impact. If only more people knew that was true.

Irfan Dhalla (UofT)@IrfanDhalla | 11:04 PM · Jun 6, 2021
95% of those over 70 in the UK have received a vaccine.
Best way to reduce hospitalizations and deaths in Canada and US and everywhere?
Make it very easy for older adults to get both first and second doses.

Eric Topol @EricTopol | 10:04 AM · Jun 5, 2021
The most encouraging data about B.1.617.2 (delta), the dominant strain in the UK, is that
despite rising cases, including over 6200 yesterday (highest since March 15),
there has yet to be an uptick in hospitalizations

Image- graph, # in UK hospital ( https://twitter.com/EricTopol/status/1401178003309142016/photo/1 )

Eric Topol @EricTopol | 11:17 AM · Jun 7, 2021:
The more we look, the neutralizing antibody response to covid infections keeps getting better:
new report 10 months or more, not significantly affected by age, severity of illness *
Image ( https://twitter.com/EricTopol/status/1401921300407357440/photo/1 )
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Hao Wang, Yu Yuan, …Tangchun Wu. 2021. Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection (Correspondence) Cellular & Molecular Immunology (June 7, 2021) https://nature.com/articles/s41423-021-00708-6

Kashif Pirzada, MD (Toronto emerg) @KashPrime | 9:47 AM · Jun 2, 2021
We've created this guide on how to protect yourself from an airborne virus using HEPA filters in offices and schools.

A simple solution that needs to be used especially in the fall/winter when opening windows and doors will be less practical:

Masks4Canada Room Ventilation and Filtration Guide
https://docs.google.com/document/d/17tKk8Da8tnchtnp9ZRe7fPazGAmXtvoA-n4GZcY0_fQ/...

Mastercard Foundation donates $1.3 billion to boost Africa’s coronavirus response
The money is intended to be used to acquire vaccines for more than 50 million people, boost the continent’s vaccine manufacturing and strengthen public health institutions.
Dan Diamond | June 8, 2021

...“Ensuring equitable access and delivery of vaccines across Africa is urgent,” Reeta Roy, (The Mastercard Foundation) CEO, said in a statement. “This initiative is about valuing all lives and accelerating the economic recovery of the continent.”

The funding, which will be distributed over three years in partnership with the Africa Centres for Disease Control and Prevention (Africa CDC), is intended to help acquire vaccines for more than 50 million of the continent’s 1.3 billion people, improve its vaccine manufacturing and delivery system and strengthen public health institutions...

...Mastercard spun off the independently operated foundation when the global financial services company went public in 2006....

https://www.washingtonpost.com/health/2021/06/08/mastercard-foundation-donation-...

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Africa Centres for Disease Control and Prevention
https://africacdc.org/

More detail than I need, but good to know that new model may point way to new therapeutics!

Scientists Discover Exactly How COVID-19 Wreaks Havoc on Human Lungs
June 8, 2021

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have published the first detailed atomic-level model of the SARS-CoV-2 “envelope” protein bound to a human protein essential for maintaining the lining of the lungs. The model showing how the two proteins interact...helps explain how the virus could cause extensive lung damage and escape the lungs to infect other organs in especially vulnerable COVID-19 patients. The findings may speed the search for drugs to block the most severe effects of the disease...

https://scitechdaily.com/scientists-discover-exactly-how-covid-19-wreaks-havoc-o...
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Jin Chai et al. 2021. Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1. Nature Communications volume 12, Article number: 3433 (8 June 2021) DOI: 10.1038/s41467-021-23533-x https://www.nature.com/articles/s41467-021-23533-x

Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence.

Biden administration to buy 500 million Pfizer coronavirus vaccine doses to donate to the world
Tyler Pager and Emily Rauhala | June 9, 2021

The Biden administration is buying 500 million doses of Pfizer’s coronavirus vaccine to donate to the world, as the United States dramatically increases its efforts to help vaccinate the global population, according to three people familiar with the plans.

President Biden is slated to announce the plan at the G-7 meeting in Britain this week amid growing calls for the United States and other rich countries to play a more substantial role in boosting the global supply of vaccines. Biden told reporters Wednesday as he boarded Air Force One to Europe he would be announcing his global vaccine strategy...

https://www.washingtonpost.com/politics/biden-vaccine-donate/2021/06/09/c2744674...

NY: SARS-CoV-2 RNA identified in specimens collected as early as 25 January 2020.
Italy: coronavirus may have been circulating as early as September 2019.
(I used to doubt a fish-pathologist who held that you will find any pathogen if you look for it...)

Matthew M. Hernandez, Ana S. Gonzalez-Reiche, …Emilia Mia Sordillo. 2021. Molecular evidence of SARS-CoV-2 in New York before the first pandemic wave. Nature Communications volume 12, Article number: 3463 (8 June 2021) https://www.nature.com/articles/s41467-021-23688-7

Abstract
Numerous reports document the spread of SARS-CoV-2, but there is limited information on its introduction before the identification of a local case. This may lead to incorrect assumptions when modeling viral origins and transmission. Here, we utilize a sample pooling strategy to screen for previously undetected SARS-CoV-2 in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across the Mount Sinai Health System in New York. The patients had been previously evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We identify SARS-CoV-2 RNA from specimens collected as early as 25 January 2020, and complete SARS-CoV-2 genome sequences from multiple pools of samples collected between late February and early March, documenting an increase prior to the later surge. Our results provide evidence of sporadic SARS-CoV-2 infections a full month before both the first officially documented case and emergence of New York as a COVID-19 epicenter in March 2020.

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Italian woman had COVID-19 in November 2019, study says
Research based on skin biopsies supports thesis that virus circulated in Europe in autumn 2019
Giada Zampano | 11.01.2021

...research by a team of scientists at the University of Milan showed that a woman in the northern Italian city was already infected with COVID-19 in November 2019.

...The first official Italian case was recorded in late February 2020. But recent studies in Italy provided additional evidence that the virus may have been spreading far earlier than initially thought, being present across Europe already in the autumn of 2019.

...A previous study by Italian scientists had detected the novel coronavirus in a 4-year-old boy’s throat secretions, following a swab test conducted in early December 2019. The child developed cold and flu-like symptoms in November and then a measles-like rash in early December.

The first COVID-19 outbreak was reported in Wuhan, China, in December last year -- although Chinese authorities have admitted that there were cases dating back to November, raising doubt over the transparency of the official data made public.

A separate study conducted in Italy last year suggested that the coronavirus may have been circulating in the country as early as September 2019.

https://www.aa.com.tr/en/latest-on-coronavirus-outbreak/italian-woman-had-covid-...

Evidence that "vaccination not only protects individuals who have been vaccinated
but also provides cross-protection to unvaccinated individuals in the community"
as seen in kids benefiting from high % of adults vaxxed

Just published @NatureMedicine
https://nature.com/articles/s41591-021-01407-5
Image -highlighted 1st p of article ( https://twitter.com/EricTopol/status/1402968040308809728/photo/1 )

- Eric Topol @EricTopol | 8:37 AM · Jun 10, 2021

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Oren Milman et al. 2021. Community-level evidence for SARS-CoV-2 vaccine protection of unvaccinated individuals. Nature Medicine (June 10, 2021) https://www.nature.com/articles/s41591-021-01407-5

Abstract
Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting individuals who have been vaccinated against the disease and possibly lowering the likelihood of transmission to individuals who have not been vaccinated. The high effectiveness of the widely administered BNT162b vaccine from Pfizer–BioNTech in preventing not only the disease but also infection with SARS-CoV-2 suggests a potential for a population-level effect, which is critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatiotemporal epidemic dynamics. Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are associated with a substantial later decline in infections among a cohort of individuals aged under 16 years, who are unvaccinated. On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold. These results provide observational evidence that vaccination not only protects individuals who have been vaccinated but also provides cross-protection to unvaccinated individuals in the community.

COVID-19: New study highlights potential role of diet
Robby Berman | June 9, 2021

...Healthcare professionals (with heavy exposure to SARS-CoV-2) eating a plant-based diet were 73% less likely to experience moderate to severe COVID-19, and those following a plant- or fish-based diet were 59% less likely to get seriously ill.

The study’s authors write, “Our results suggest that a healthy diet rich in nutrient-dense foods may be considered for protection against severe COVID-19.”..

https://www.medicalnewstoday.com/articles/covid-19-new-study-highlights-potentia...

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Kim H, Rebholz CM, Hegde S, et al. 2021. Plant-based diets, pescatarian diets and COVID-19 severity: a population-based case–control study in six countries. BMJ Nutrition, Prevention & Health 2021;0. doi:10.1136/bmjnph-2021-000272 https://nutrition.bmj.com/content/bmjnph/early/2021/05/18/bmjnph-2021-000272.ful...

Abstract
...Results ...After adjusting for important confounders, participants who reported following ‘plant-based diets’ and ‘plant-based diets or pescatarian diets’ had 73% (OR 0.27...) and 59% (OR 0.41...) lower odds of moderate-to-severe COVID-19 severity, respectively, compared with participants who did not follow these diets. Compared with participants who reported following ‘plant-based diets’, those who reported following ‘low carbohydrate, high protein diets’ had greater odds of moderate-to-severe COVID-19 (OR 3.86...). No association was observed between self-reported diets and COVID-19 infection or duration.

Conclusion In six countries, plant-based diets or pescatarian diets were associated with lower odds of moderate-to-severe COVID-19. These dietary patterns may be considered for protection against severe COVID-19.

...DISCUSSION

... Plant-based diets are rich in nutrients, especially phytochemicals (polyphenols, carotenoids),...with prior studies reporting higher fibre, vitamins A, C, and E, folate, and mineral (iron, potassium, magnesium) intake among those with highest versus lowest adhe-ence to plant-based diets... Studies have reported that supplementation of some of these nutrients, specifically, vitamins A, C, D, and E, decreased the risk of respiratory infections, such as the common cold and pneumonia, and shortened the duration of these illnesses.... These nutrients are hypothesised to support the immune system as they play important roles in the production of antibodies, proliferation of lymphocytes, and reduc-tion of oxidative stress... While previously, both specific micronutrient deficiencies as well as generalised malnutrition have been associated with immune dysfunction in the host, the viral pathogen itself may be affected by the nutritional deficiency as well... Multiple viruses, such as coxsackievirus and influenza, have been shown to develop increased virulence due to changes in their genomes as a consequence of replicating in a nutritionally deficient host (eg, deficiency in selenium)... Selenium may be an important nutrient to consider, considering its role in immunity... Given our findings of protection from severe illness in those consuming a micronutrient-dense diet, our data support this hypothesis. We could not further explore individual nutrient levels in our study population because we did not have these data. Future studies with detailed information on plasma micronutrient levels are warranted to confirm our findings.

Along with plant-based diets, individuals who reported following pescatarian diets had lower odds of severe COVID-19. Pescatarian diets lie within the spectrum of plant-based diets and include fish or seafood while restricting the intake of meats... Fish intake is an important source of vitamin D and omega-3 fatty acids, that is, eicosapentaenoic acid (EPA) and docosahex-aenoic acid (DHA). High EPA and DHA intake, which results in high omega-3 fatty acids compared with omega-6 fatty acids and formation of omega-3 oxylipins,29 have anti-inflammatory effects, suppressing the production of pro-inflammatory cytokines (interleukin 1β, tumour necrosis factor α), reducing inflammatory eicosanoid synthesis and oxidative stress... A meta-analysis of 10 randomised controlled trials in patients with acute respiratory distress syndrome (ARDS) found that individuals who received formulas high in omega-3 fatty acid had shorter duration of mechanical ventilation and shorter length of stay at intensive care units,... suggesting favourable effects of omega-3 fatty acids on ARDS. In our study, the magnitude of the association for moderate-to-severe COVID-19 illness was lower when we included pescatarian diets in addition to those who reported following plant-based diets. Our results suggest that although there is evidence that fish intake may have favourable impacts on respiratory illness, future studies are needed to confirm whether pescatarian diets are associated with patient outcomes in the context of COVID-19.

Interestingly, when we restricted cases to those with a positive PCR or antibody test, individuals who reported following plant-based diets or pescatarian diets had lower odds of COVID-19 infection. Epidemiological studies have shown that fruit and vegetable intake is associated with a lower risk of upper respiratory tract infection such as cold, influenza, or sinusitis... Some studies reported that higher intake of fish was inversely associated with respiratory conditions such as asthma and chronic obstructive pulmonary disease... However, considering the lack of data on dietary intake and COVID-19 in the literature, and the smaller number of cases when we defined cases solely by testing, the result on COVID-19 infection requires replication.

Low carbohydrate, high protein diets were associated with non-significant greater odds of severe COVID-19 when compared with those who did not report following these diets. However, when we compared these diets to plant-based diets, those who reported following low carbohydrate, high protein diets had significantly greater odds of moderate-to-severe COVID-19. Participants who reported following low carbohydrate, high protein diets had a higher intake of legumes, nuts, soups, and animal products such as eggs and poultry. Studies have hypothesised that an unhealthy dietary pattern, such as Western diets which are high in refined sugars, processed foods, and red and processed meats, can be pro-inflammatory and have negative health impacts... Without plasma micronutrient levels, it is unclear whether low carbohydrate, high protein diets are unhealthy. Nonetheless, our results highlight that it may be advisable to follow a healthy dietary pattern such as plant-based diets or pescatarian diets. Our study has several strengths, including a large sample size, diverse HCWs from multiple countries, and careful adjustment of potential confounding factors. Further, we were able to capture the early phase of the global pandemic, before the detection of known SARS-CoV2 variants of concern, which could further complicate a multinational epidemiological analysis, by leveraging an existing network of HCWs. However, our finding should be interpreted within the context of the following limitations. First, we relied on participants’ self-report to define exposures and outcomes. As such, there is a possibility of recall bias. However, HCWs are unique in that they may be a source of high-quality data (eg, complete informa-tion, probably high accuracy of information)... Second, the definition of certain dietary patterns (eg, plant-based diets, pescatarian diets, low carbohydrate, high protein diet) may vary by countries. Nevertheless, it is encouraging that the responses on the food frequency questionnaire reflected intake of food groups that are consistent with these dietary patterns. Third, our study may not have included individuals with more severe COVID-19 illness, given that severe cases (mechanical ventilation, admission to intensive care units) may not have been able to complete our questionnaire. Fourth, our study population comprised predominantly male physicians; thus, the findings of the study may need to be replicated in women and non-HCWs. Lastly, despite our efforts to adjust for a number of confounding factors, residual confounding may still be present due to unmeasured or incorrectly assessed variables.

In conclusion, individuals who reported following plant-based diets or pescatarian diets had lower odds of severe COVID-19-like illness. Individuals who reported following low carbohydrate, high protein diets had higher odds of severe-COVID-19-like illness, when compared with individuals who followed plant-based diets. Those who reported following plant-based diets or pescatarian diets had higher intake of vegetables, legumes and nuts, and lower intake of poultry and red and processed meats. Our results suggest that a healthy diet rich in nutrient-dense foods may be considered for protection against severe COVID-19. Future studies with detailed macro- and micronutrient data are warranted to study associations between dietary intake and COVID-19 severity.

UK cases double over past week as Delta variant dominates
Oliver Barnes | June 10, 2021

Covid-19 cases in the UK have more than doubled in the past week, rising to above 11,000 a day, driven by infections among unvaccinated people, according to an epidemiological study.

The Zoe Covid study estimated there are 11,908 symptomatic cases a day in the UK and that the reproduction rate of Covid-19, or R value, has risen to 1.3 from 1.1, meaning for every 10 people infected they pass the virus on to 13 others.

Tim Spector, a professor of genetic epidemiology at King’s College London and lead author of the study, said: “The UK has rapidly changed from one of the best performing nations to a nation again struggling with rising cases.”

He attributed the sharp rise in infections to increased social mixing and the highly transmissible Delta variant of the virus, first identified in India, which is now the dominant strain in the UK.

Matt Hancock, the UK health secretary, said on Thursday the variant accounts for 91 per cent of all new cases in the UK.

Spector said Covid-19 had become “an epidemic among the unvaccinated and partially vaccinated populations in the UK”, adding that fully vaccinated people had “much greater protection”.

The risk of infection was only one in 22,455 for people who had received both doses of a Covid-19 vaccine, according to the study, but rose to one in 7,901 when only a single dose had been administered and one in 2,908 for unvaccinated people.

https://www.ft.com/content/c52a1cf1-d3e7-4291-b08f-9b44b520367d

CDC to review potential link between heart inflammation and mRNA vaccines

...The CDC’s Advisory Committee on Immunization Practices will discuss the issue after a small percentage of vaccinated people — many of them teenagers or young adults — experienced a condition called myocarditis. On Thursday, the CDC said it had identified 216 cases of heart inflammation after an initial dose of an mRNA vaccine and another 573 cases after the second shot. More than 130 million people have been fully vaccinated with mRNA vaccines made by U.S. firms Pfizer, with German partner BioNTech, and Moderna...

https://www.washingtonpost.com/nation/2021/06/11/coronavirus-covid-live-updates-...
https://www.cdc.gov/vaccines/acip/meetings/downloads/agenda-archive/agenda-2021-...

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ETA:
David Fisman (U Toronto) @DFisman | 5:56 AM · Jun 11, 2021:
Updated US data on myocarditis/pericarditis after mRNA vaccine from yesterday’s FDA review.
Tldr: the signal is real, most (80%) recover fully, but not all.
Risk greatest in young males (16-24) after 2nd dose

https://fda.gov/media/150054/download

("We can’t connect to the server at fda.gov." margd: Will try again later.)

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Kashif Pirzada, MD (Emerg Toronto) @KashPrime | 8:08 AM · Jun 11, 2021:
Forgoing the second dose of mRNA vaccine for teens and young adults might be the safer way to go, as Israel is trialing right now

Vitamin D not associated with COVID-19 susceptibility and severity in people of European descent not deficient in the vitamin.

Guillaume Butler-Laporte et al. 2021. Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study. PLOS (June 1, 2021) https://doi.org/10.1371/journal.pmed.1003605 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003605

Abstract
Background
Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity.

Methods and findings
Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio (OR) = 0.95...), hospitalization (OR = 1.09; ...), and severe disease (OR = 0.97). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency.

Conclusions
In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.

Potential New SARS-CoV-2 Pandemic(s) in the Making?

Researchers in China say they have uncovered a new batch of coronaviruses in bats that resembles the COVID-19 virus that has swept the globe. Question: Is this honest research, or an attempt to distract from China's dishonest representations to WHO, or are we looking at a future of successive pandemics from environmentally stressed host species' infestations of COVID-like viruses?

The researchers published their findings in the journal, Cell.

. . .they collected samples from small bats that lived in forests in the Yunnan province between May 2019 and November 2020. The samples consisted of urine, feces and mouth swabs.

"In total, we assembled 24 novel coronavirus genomes from different bat species, including four SARS-CoV-2 like coronaviruses

One strain, garnered from the Rhinolophus pusillus bat species, bears a particularly strong resemblance to SARS-CoV-2, though with differences on the spike protein that the viruses use to attach to cells they infect.

"Together with the SARS-CoV-2 related virus collected from Thailand in June 2020, these results clearly demonstrate that viruses closely related to SARS-CoV-2 continue to circulate in bat populations, and in some regions might occur at a relatively high frequency. . .

Mark Gilmore (BSc, plumber, gas technician, hi rise service) @markegilmore
https://twitter.com/markegilmore/status/1403564633424809985 (with comments, images, links )
https://threadreaderapp.com/thread/1403564633424809985.html (with images, links)

Some thoughts on ventilation and cross contamination of air between mid/high-rise suites that I've observed over 10 years of working in condos, apartments, hotels, and group homes.
So you've checked that the ventilation in your suite is working but where is that air going? /1

Many exhaust ducts especially in older buildings break and become disconnected inside wall and ceiling spaces. Let's remember many of these ducts are held together with a few screws and "duct tape". /2

Drains, drain stacks and water supply risers are replaced for renos and repairs. The sleeves (holes through the concrete floor which pipes/ducts travel through) are supposed to be sealed as per local fire code but that is up to the repair tech and is almost never inspected. /3

Exhausted air from suites can fill wall cavities, pass between floors, and enter neighbouring suites through gaps around drains, water lines, access doors or ceiling vents. /4

Sanitary plumbing vent stacks can also break inside walls allowing contaminated air to leak into wall and ceiling spaces and penetrate into suites through the cracks and gaps displayed previously. /5

I've seen neglected, poorly managed and maintained buildings with make up air supplying suites from hallways combine with ventilation in suite issues create suites so negatively pressurized and deprived of air they begin to pull air from every possible source. /6

Sometimes these negatively pressurized suites can pull air from sanitary drain stack from under loose rockings toilet with a dried out toilet gasket seal. /7

Makes for one smelly bathroom!

I was first skeptical when many suggested Covid could pass between high rise residential neighbouring suites.
I'm not an expert in aerosol transmission but what I have come to believe is that there is enough convincing evidence that #COVIDisAirborne /8

There have been numerous outbreaks in high rise residential buildings with too many cases to simply dismiss airborne transmission from suite to suite. /9 *

What I've tried to highlight in this thread with photos I've taken and evidence I've seen working throughout this pandemic and before is that in my experience there are numerous routes for an airborne transmitted virus like Covid to travel from residential suite to suite. /10

I hope this thread helps inform and adds to the growing evidence that a disease that can be transmitted through the air has more than enough routes to pass from suite to suite in high-rise residential buildings. /11

Replying to
@markegilmore
Thanks to all those who have educated so many about aerosol transmission and air movement and those who have faced enormous criticism for their advocacy and beliefs. /12
@jljcolorado
@linseymarr
@kprather88
@DFisman
@jmcrookston
@DavidElfstrom
@smjevnikar
@healthyheating

Here is an even better thread from an Engineer on the risks of Covid spread through multi-unit residential buildings.... https://twitter.com/DavidElfstrom/status/1379814589395795975 /End

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* Health Department monitoring COVID spike at Whitby’s Highland Towers apartments
Moya Dillon | May 25, 2021

...The Durham Region Health Department is monitoring increasing cases of COVID-19 at Whitby’s Highland Towers Apartments.

Since the beginning of the month 143 positive cases have been confirmed at the complex, including 43 new cases following an on-site testing centre held May 20...

https://www.thestar.com/local-whitby/news/2021/05/25/health-department-monitorin...

Eric Topol @EricTopol | 3:23 PM · Jun 12, 2021
Besides the 3rd wave in South Africa, many other countries in Africa are showing signs of increasing covid spread

@OurWorldInData
https://wsj.com/articles/africa-awaits-covid-19-vaccine-donations-as-cases-surge...
by @gksteinhauser @Nicholasbariyo @JoeWSJ

Image-graph, cases March 2020 - June 2021, 8 African countries ( https://twitter.com/EricTopol/status/1403795023091539974/photo/1 )
Image-headline, Uganda photo ( https://twitter.com/EricTopol/status/1403795023091539974/photo/2 )

Transmissibility of variants:
The UK variant is 2X transmissible as Wuhan.
The Indian variant is 2X transmissible as UK and 4X as India.
(One can catch measles by walking into room 2 HOURS after a measles patient, if I recall correctly.)

Image--infographic, relative transmissibility of variants ( https://twitter.com/EricTopol/status/1403725152357998600/photo/1 )

R0 is the number of cases, on average, an infected person will cause during their infectious period.
Alpha = B117, first reported in UK
Delta = B.1.617.2, first reported in India

>8 margd: contd

The Latest: WHO chief says vaccine need outstrips G7 pledges
The Associated Press | 6/12/2021

...“The challenge, I said to the G-7 leaders, was that to truly end the pandemic, our goal must be to vaccinate at least 70% of the world’s population by the time the G-7 meets again in Germany next year,” WHO Director-General Tedros Adhanom Ghebreyesus told reporters Saturday at the summit in southwest England.

“To do that, we need 11 billion doses,” Tedros said, adding that it was “essential” for countries to temporarily waive intellectual property protections for coronavirus vaccines.

British Prime Minister Boris Johnson, the summit’s host, has said the group would pledge at least 1 billion doses, with half that number coming from the United States and 100 million from Britain over the next year. (margd: I think I read that Canada has also pledged 100 million doses? That's enough to vaxx Canadians with two doses--and then some. ETA: https://www.cbc.ca/news/politics/vaccine-donations-g7-1.6061844 )
)

Tedros reiterated his target of vaccinating 30% of the population of every country by the end of 2021. He said that reaching the goal requires 100 million doses in June and July, and 250 million more by September...

https://apnews.com/article/government-and-politics-joe-biden-europe-g-7-summit-b...

A lot of vaccine hesitancy in Russia, so uptick in delta variant (B.1.617.2, first reported in India) is especially bad news.

Eric Topol @EricTopol | 6:48 PM · Jun 12, 2021:
Russia now confronting the delta variant with its highest cases (today >13 margd:,500) since February

CoVariants: per variant/country (Last updated: 2021-06-11)
http://covariants.org (green is delta)

Image-graph ( https://twitter.com/EricTopol/status/1403846739715530754/photo/1 )
Image-graph ( https://twitter.com/EricTopol/status/1403846739715530754/photo/2 )
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Mike Honey @Mike_Honey_ | 9:36 PM · Jun 12, 2021:
More detailed data confirms the delta surge in Russia.
Zoomed in to April 2021 onwards, top 3 variants by overall frequency, delta in red.

Data from http://microreact.org for this dataviz project:
https://github.com/Mike-Honey/covid-19-genomes#readme
Image-graph ( https://twitter.com/Mike_Honey_/status/1403888976553906179/photo/1 )
_________________________________________________

Over 60 per cent of Russians don't want Sputnik V vaccine, see COVID-19 as biological weapon: poll
Reuters | March 1, 2021 12:34 p.m. ET

https://beta.ctvnews.ca/national/coronavirus/2021/3/1/1_5328758.html

>18 margd: contd.
In initial outbreak, Wuhan suffered mildest of the variants. MDs in se China say patients with Delta (B.1.617.2, first reported in India) are becoming sicker and their conditions are worsening much more quickly:

In China’s latest outbreak, doctors say the infected get sicker, faster.
Keith Bradsher | June 12, 2021

As the Delta variant of the coronavirus spreads in southeastern China, doctors say they are finding that the symptoms are different and more dangerous than those they saw when the initial version of the virus started spreading in late 2019 in the central city of Wuhan...

https://www.nytimes.com/2021/06/12/world/china-covid-delta-variant-guangzhou.htm...

> 20 Russia

Meanwhile in the US...

Eric Topol @EricTopol | 10:54 AM · Jun 13, 2021
The one variant on a steep rise in the US is delta (B.1.617.2, India) currently ~10% of sequenced cases,
doubling every 7-10 days to become dominant.
As B.1.1.7 (alpha, UK) fades.
And P.1 (gamma, Brazil & BC) also rising.

https://cov-spectrum.ethz.ch/explore/United%20States/AllSamples/AllTimes/variant...
Image-graphs variants in US ( https://twitter.com/EricTopol/status/1404089689934471171/photo/1 )

UK v Israel:

Eric Topol @EricTopol | 11:15 AM · Jun 13, 2021
Why did the UK and Israel, 2 countries with very high vaccination rates, have such different results?
Israel currently 0.2 cases/100,000 people without lockdown, UK 10/100K, delaying reopening
One reason is the delta variant

Image-graph, # cases UK, Israel ( https://twitter.com/EricTopol/status/1404095178621669376/photo/1 )
Image-graph, variants UK, Israel ( https://twitter.com/EricTopol/status/1404095178621669376/photo/2 )

>15 Limelite: Another reason to push research on a broad-spectrum vaccine against coronaviruses in general:

https://www.sciencemag.org/news/2021/04/vaccines-can-protect-against-many-corona...

We must remember that in its acute and long forms, COVID commonly inflames heart tissue. And COVID inflammation can be quite persistent and severe, even deadly.

Europe reports rare cases of heart inflammation linked to all COVID-19 vaccines
Dulan Lokuwithana | Jun. 12, 2021

The safety committee of the European Medicines Agency (EMA) has requested more information from developers after detecting myocarditis and pericarditis in a small number of people following the vaccination with all COVID-19 shots.

Most of the cases were mild and resolved within a few days, the EMA said adding that they affected mostly males below the age of 30 years within several days of the second COVID-19 shot.

Myocarditis and pericarditis are inflammatory conditions of the heart that can result in symptoms such as shortness of breath and chest pain. They can follow infections or immune diseases.

“Currently, further analysis is needed to conclude whether there is a causal relationship with the vaccines,” the EMA noted in the statement.

The cases of pericarditis stood at 126, 18, 47 and one for vaccines from Pfizer/BioNTech, Moderna, AstraZeneca, and Johnson & Johnson (NYSE:JNJ), after the administration of 160M, 19M, 40M, and 2M doses in the region, respectively.

The U.S. Centers for Disease Control and Prevention (CDC) has convened a meeting of an expert panel this week to further discuss the rare cases of heart inflammation following the second dose of messenger-RNA COVID-19 vaccines...

https://seekingalpha.com/news/3705837-europe-reports-rare-cases-of-heart-inflamm...

Live Bats in Cages at Wuhan Lab?

In a follow up to my previous post regarding the relationship between bats and SARS-CoV-2 type viruses comes news via Sky News Australia - video taken inside the laboratory in the Wuhan Institute of Virology apparently shows live bats kept in cages. This footage, if genuine, proves that China lied when it reported to WHO that such a thing had not been done.

Keep in mind Sky News is a right wing news source. The video is attributed to the Chinese Academy of Sciences and allegedly dates from May 2017. I hardly need point out that there were years between then and the outbreak at the end of 2019. During that time, Chinese scientists had plenty of time to have removed them. In addition, the scene in the 10 minute video could have been staged as an example of what NOT to do. Context is absent.

The video shows bats being held in a cage at the Wuhan Institute of Virology, along with vision of a scientist feeding a bat with a worm.
(SNIP)
The World Health Organisation report investigating the origin of the pandemic failed to mention that any bats had been kept at the Wuhan Institute of Virology and only its annex referred to animals being housed there.

“The animal room in the P4 facility can handle a variety of species, including primate work with SARS-CoV-2,” it states.

Obviously, the annex is not actually the lab space. Obviously, primate work with SARS-CoV-2 has nothing to do with bats, which are not primates. Obviously, this is a very sloppy piece of pseudo-journalism aimed at the Q-crowd and is designed to sensationalize a small video that may only be of historical value and not evidentiary to the issue of the origins of the current pandemic.

The story is a mish-mash that includes unattributed or unidentified "sources" who adopt pseudonyms and have no identifiable credentials as credible investigative reporters. It's primary value may be as a cautionary lesson regarding "blockbuster discoveries" that are concocted to take advantage of the spotlight on SARS-CoV-2 origin myths hitched to actual research demonstrating the bat-virus relationship in an attempt to draft a piece of fiction behind a substantial mass of fact.

Stay tuned.

Dr. Tom Frieden (frmr CDC Director) @DrTomFrieden | 12:18 PM · Jun 14, 2021:
The world needs all the vaccines we can get.
The Novavax announcement today is very encouraging—remarkably high efficacy, including against variants of concern,
with no safety concerns detected in clinical trials of nearly 30,000 people.

Novavax Offers U.S. a Fourth Strong Covid-19 Vaccine
The company’s large U.S. trial found an efficacy rate of about 90 percent. But at this point, the nation is awash in other shots.
Carl Zimmer | June 14, 2021

...In the 29,960-person trial, the vaccine demonstrated an overall efficacy of 90.4 percent, on par with the vaccines made by Pfizer-BioNTech and Moderna, and higher than the one-shot vaccine from Johnson & Johnson. The Novavax vaccine showed an efficacy of 100 percent at preventing moderate or severe disease.

...Novavax would probably win its first authorization elsewhere (than US). The company is also applying in Britain, the European Union, India and South Korea.

...many vaccine experts expect that, with waning immunity and emerging variants, the country will need booster shots at some point. And the protein-based technology used in the Novavax vaccine may do a particularly good job at amplifying protection, even if people have previously been vaccinated with a different formulation. ( A new version of the vaccine contains the proteins from the Beta variant first identified in South Africa. * )

...The vaccine’s side effects were relatively mild. Some volunteers reported fatigue, headaches and other minor symptoms.

...the company plans on making 100 million doses per month by the end of the third quarter, and 150 million doses per month by the end of the fourth quarter....

https://www.nytimes.com/2021/06/14/health/covid-vaccine-novavax.html
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* James Logue et al. 2021. Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants. BioRxiv (June 9, 2021) doi: https://doi.org/10.1101/2021.06.08.447631

Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally. As SARS-CoV-2 has transmitted from person to person, variant viruses have emerged with elevated transmission rates and higher risk of infection for vaccinees. We present data showing that a recombinant prefusion-stabilized Spike (rS) protein based on the B.1.351 sequence (rS-B.1.351) was highly immunogenic in mice and produced neutralizing antibodies against SARS-CoV-2/WA1, B.1.1.7, and B.1.351. Mice vaccinated with our prototype vaccine NVX-CoV2373 (rS-WU1) or rS-B.1.351 alone, in combination, or as a heterologous prime boost, were protected when challenged with live SARS-CoV-2/B.1.1.7 or SARS-CoV-2/B.1.351. Virus titer was reduced to undetectable levels in the lungs post-challenge in all vaccinated mice, and Th1-skewed cellular responses were observed. A strong anamnestic response was demonstrated in baboons boosted with rS-B.1.351 approximately one year after immunization with NVX-CoV2373 (rS-WU1). An rS-B.1.351 vaccine alone or in combination with prototype rS-WU1 induced protective antibody- and cell-mediated responses that were protective against challenge with SARS-CoV-2 variant viruses.

AMA: 96% Of Doctors Are Vaccinated Against Covid-19
Bruce Japsen | June 11, 2021
https://www.nytimes.com/2021/06/14/health/covid-vaccine-novavax.html

Delta coronavirus variant doubles risk of hospitalization: Scottish study
Helen Collis | June 14, 2021
https://www.politico.eu/article/delta-coronavirus-variant-doubles-risk-of-hospit...
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Aziz Sheikh et al. 2021. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness (Corrspondence). The Lancet (June 14, 2021) DOI:https://doi.org/10.1016/S0140-6736(21)01358-1
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fullt...

...In summary, we show that the Delta VOC (B.1.617.2, first reported in India) in Scotland was found mainly in younger, more affluent groups. Risk of COVID-19 hospital admission was approximately doubled in those with the Delta VOC when compared to the Alpha VOC (B117 first reported in UK), with risk of admission particularly increased in those with five or more relevant comorbidities. Both the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines were effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalisation in people with the Delta VOC, but these effects on infection appeared to be diminished when compared to those with the Alpha VOC. We had insufficient numbers of hospital admissions to compare between vaccines in this respect. The Oxford–AstraZeneca vaccine appeared less effective than the Pfizer–BioNTech vaccine in preventing SARS-CoV-2 infection in those with the Delta VOC. Given the observational nature of these data, estimates of vaccine effectiveness need to be interpreted with caution.

>29 margd: Also, for those who are fully vaccinated, the protection from Delta variant is excellent. But the protection effectiveness for those who have only had one jab drops off markedly. COVID-19 and its variants are driving home the lesson, "Take ALL your medication, even if you feel you don't need it."

Hope that next fall, Delta variant (B.1.617.2, first reported in India) doesn't find us once again whistling past the graveyard...

U.S. COVID-19 deaths cross painful 600,000 milestone as country reopens
Sharon Bernstein | June 14, 2021

The United States has now lost over 600,000 mothers, fathers, children, siblings and friends to COVID-19, a painful reminder that death, sickness and grief continue even as the country begins to return to something resembling pre-pandemic normal...about 15% of the world’s total coronavirus fatalities of around 4 million, a Reuters tally shows.

...The rate of severe illness and death has dropped dramatically as more Americans have become vaccinated, creating something of a psychological whiplash that plagues the millions whose lives have been touched by the disease. Many are eager to emerge from more than a year of sickness and lockdown, yet they still suffer - from grief, lingering symptoms, economic trauma or the isolation of lockdown...

https://www.reuters.com/world/us/us-covid-19-deaths-cross-painful-600000-milesto...

‘This gives hope’: A third COVID-19 vaccine dose can boost protection for organ transplant recipients
Jennifer Couzin-Franke l Jun. 14, 2021

...After one dose of a highly effective messenger RNA (mRNA) vaccine, for example, just 17% of (organ transplant) patients churned out protective antibodies against the pandemic coronavirus, and after the standard two doses, only 54% did. The very medications ...patients took to protect their transplanted organ precluded them from mounting a healthy immune response after the vaccine. Even people who did make the antiviral antibodies often had very low levels, raising questions about how well they were shielded from COVID-19.

But now (transplant surgeon Dorry) Segev, at Johns Hopkins University, has become cautiously optimistic. He and his colleagues have found that a third dose of vaccine may help: Among 24 organ transplant patients who had no antibodies after two doses, eight people generated protective antibodies after they sought out a third on their own. Six people who had few antibodies against the coronavirus after two doses all wound up with high levels after a third shot, the researchers reported today in the Annals of Internal Medicine.

Although Segev didn’t conduct a systematic study—the 30 patients got combinations of different vaccines at different time intervals—“this gives hope, which is critical right now,” he says. “There is some encouraging evidence that we will be able to help the immune system do what it needs to do.”...

doi:10.1126/science.abj9828
https://www.sciencemag.org/news/2021/06/gives-hope-third-covid-19-vaccine-dose-c...

-------------------------------------------------------------

William A. Werbel et al. 2021. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series (Letter). Annals of Internal Medicine (15 June 2021) https://doi.org/10.7326/L21-0282 https://www.acpjournals.org/doi/10.7326/L21-0282

Researchers found a marker of nerve injuries in 142 patients with #COVID19—some without overt neurological symptoms. The results could help explain why some COVID-19 patients experience long-term neurological issues.
- Science Magazine @ScienceMagazine | 10:05 AM · Jun 15, 2021
------------------------------------------------------------------

Mercedes Prudencio et al. 2021. Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19. Science Translational Medicine 15 Jun 2021: eabi7643
DOI: 10.1126/scitranslmed.abi7643 https://stm.sciencemag.org/content/early/2021/06/14/scitranslmed.abi7643

Abstract

Brain imaging studies of patients with COVID-19 show evidence of macro- and micro-hemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In one hundred hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

>29 margd:

Image-table, 1 & 2-dose Pfizer & AstraZeneca efficacy against delta (B.1.617.2, first reported in India) & alpha (B117, UK)
( https://twitter.com/VincentRK/status/1404792291248771078/photo/1 )

New (Scotland) @P_H_S_Official data published in @TheLancet >29 margd: show
...Similar results to England @PHE_uk (thread 21 #44)

- Vincent Rajkumar (Mayo) @VincentRK | 9:25 AM · Jun 15, 2021

AMA survey shows over 96% of doctors fully vaccinated against COVID-19
Jun 11, 2021

...more than 96 percent of surveyed U.S. physicians have been fully vaccinated for COVID-19, with no significant difference in vaccination rates across regions. Of the physicians who are not yet vaccinated, an additional 45 percent do plan to get vaccinated...

https://www.ama-assn.org/press-center/press-releases/ama-survey-shows-over-96-do...

>35 margd: One wonders what that 45% of the unvaccinated 4% are waiting for

Is SARS-CoV-2 infection in pets more common than we thought?
James Kingsland | June 11, 2021

A small study that repeatedly tested the pets of people with COVID-19 suggests that 31% of dogs and 40% of cats acquired a SARS-CoV-2 infection.

Neutered pets or those that shared a bed with a human with the infection were more likely to contract the infection.

The study reinforces the message that people with COVID-19 should avoid close contact with their pets if possible.

There remains no evidence that pets with the infection can pass it on to people or other animals.

...Pets in 10 of the households (around 50%) tested positive for the virus. In total, there were nine dogs (31% of all the dogs) and four cats (40% of all the cats) that contracted the infection...

https://www.medicalnewstoday.com/articles/is-sars-cov-2-infection-in-pets-more-c...

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Guilherme Amaral Calvet et al. 2021. Investigation of SARS-CoV-2 infection in dogs and cats of humans diagnosed with COVID-19 in Rio de Janeiro, Brazil. PLOS ( April 28, 2021 ) https://doi.org/10.1371/journal.pone.0250853 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250853

Wonder how Americans will prove vaxx and COVID status to EU and Cdn border controls if US vaxx passports continue to be blocked? Could be huge waits if border guards have to verify status of each passenger individually... EU and Canada might issue something like a NEXUS pass for frequent visitors??

12 Countries Using EU’s Digital COVID Certificate, 16 More Ready To Go
Laurie Baratti June 13, 2021. Updated June 14.

...The European Commission approved the launch of this new digital vaccination verification tool back in May to harmonize COVID-19 entry regulations within the 27-nation bloc, thereby facilitating travel and supporting freer movement across the continent at a time that’s critical for the tourism sector.

The E.U. Digital COVID Certificate is essentially a free mobile app that supplies on-demand either: digital proof of a person’s vaccination against COVID-19, recent negative test results or certification that they’ve previously been clinically diagnosed and recovered from the virus.

The certificate displays certain key information—including the traveler’s name, date of birth and date of issue—and produces a unique QR code that pulls up relevant documentation or linked reporting portals (from a hospital, laboratory, test center, etc.). The European Commission website asserts that this data remains of the certificate but isn’t stored or retained by visited countries. The person’s health data, meanwhile, remains securely on file with the member state that issued the E.U. Digital Health Certificate.

In the interest of convenience, a digital version can be stored on a mobile device, or, alternatively, a paper version can be requested. E.U. member states have agreed upon a common design for both the electronic and printed versions to help speed recognition of the credential. Health authorities in individual member countries are responsible for issuing the certificates and making them available to citizens.

...While it would seem that a streamlined digital passport for European travel wouldn’t be of help to U.S. visitors, an E.U. spokesperson actually stated earlier this month that the app could potentially be made available to non-E.U. citizens, Forbes reported. Again, the decision on whether to extend use of the app to travelers from outside the E.U. would rest with individual member nations.

“Right now, if you’re an American not living in the E.U., you could get the certificate if you ask the national authorities of a member state to give you that certificate, based on some proof that you’ve been vaccinated, or had a recent COVID test,” the unnamed E.U. spokesperson postulated.

https://www.travelpulse.com/news/impacting-travel/12-countries-using-eus-digital...

Good article on long Covid / post-acute Covid-19 syndrome:

What Covid-19's long tail is revealing about disease
David Cox | 9th June 2021

..The most common symptom, which (Melissa Heightman, University College London Hospitals) says was experienced by more than 80% of patients in her clinic, is a deadening fatigue which impairs their life, making it difficult to complete the simplest of daily tasks...The general scientific consensus is that around one in 10 Covid-19 patients will still have symptoms 12 weeks later.

...two very disparate patient groups – those who were admitted to hospital and those who weren't – each with different underlying causes.

The former group has proven far more straightforward for doctors to manage. Typically their lungs or heart have been damaged by either the acute viral infection, or the resulting cytokine storm – the severe inflammatory response that can cause a patient's immune system to attack their own tissues. Computerised tomography (CT) and Magnetic Resonance Imaging (MRI) scans swiftly reveal the extent of the damage, while drugs such as colchicine can be used to dampen down any lingering inflammation in the internal organs.

Heightman says that two thirds of the UCLH clinic's long Covid patients admitted to hospital are now recovering well, while the remaining third have seen improvements in their scans after six months.

"We expect the vast majority of these patients will improve to the point that they shouldn't be left with damage that limits their life," she says. "We hope that less than 10%, those who were in the ICU for a long time, will be left with any permanent heart or lung abnormality."

But the non-hospital patients with long-term symptoms have proven far more perplexing.

According to Heightman, the peak age tends to be between 35 and 49, and they report a mysterious range of symptoms. Some surveys of patients have identified up to 98 different symptoms. The most common include fatigue, brain fog, muscle and joint pain, sleep disturbances, migraines, chest pain, skin rashes, new sensitivities to smells and tastes, and dysautonomia, a normally rare condition which causes an uncomfortable and rapid increase in heartbeat when they attempt any form of activity.

Heightman says that while 50% of UCLH's long Covid patients who were not admitted to hospital have improved over the course of a year to the point that they can manage their symptoms alone, the remaining half are still unwell.

While half of Heightman's patients have made a good recovery, others have not been so fortunate. A recent survey from the PLRC (Patient-Led Research Collaborative) painted a bleaker picture. Out of 3,762 long Covid patients, 77% were still experiencing fatigue after six months, 72% were struggling with post-exertional malaise, 55% were suffering from cognitive dysfunction, while 36% of female patients experienced menstrual cycle issues. "My own cycle disappeared for three months," says Hannah Wei, part of the PLRC leadership team, who herself suffered from long Covid over the past year.

The survey identified that for many long Covid patients who were not admitted to hospital, symptoms come and go in three separate waves. This pattern begins with a dry cough and fever, followed swiftly by a second wave of new symptoms such as dysautonomia, which peak after two months and then taper off. A month after the initial infection, a third wave of symptoms appears, including skin rashes, muscle pain, new allergies, and brain fog. "This is the most concerning, because this wave of symptoms just continues to get gradually worse, peaking at around four months, and then just keeps going," says Wei.....

https://www.bbc.com/future/article/20210609-how-long-will-long-covid-last

Many Post-Covid Patients Are Experiencing New Medical Problems, Study Finds
Pam Belluck | June 15, 2021

...The study,* tracking the health insurance records of nearly two million people in the United States who contracted the coronavirus last year, found that one month or more after their infection, almost one-quarter — 23 percent — of them sought medical treatment for new conditions.

Those affected were all ages, including children. Their most common new health problems were pain, including in nerves and muscles; breathing difficulties; high cholesterol; malaise and fatigue; and high blood pressure. Other issues included intestinal symptoms; migraines; skin problems; heart abnormalities; sleep disorders; and mental health conditions like anxiety and depression.

Post-Covid health problems were common even among people who had not gotten sick from the virus at all, the study found. While nearly half of patients who were hospitalized for Covid-19 experienced subsequent medical issues, so did 27 percent of people who had mild or moderate symptoms and 19 percent of people who said they were asymptomatic.

...More than half of the 1,959,982 patients whose records were evaluated reported no symptoms from their Covid infection. Forty percent had symptoms but didn’t require hospitalization, including 1 percent whose only symptom was loss of taste or smell; only 5 percent were hospitalized...

https://www.nytimes.com/2021/06/15/health/covid-19-patients.html
----------------------------------------------------------------------
WHITE PAPER
An Analysis of Private Healthcare Claims: A Detailed Study of Patients with Long-Haul COVID
A FAIR Health White Paper, June 15, 2021
33p
https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/A%20Detailed%20S...

Red Cross needs donors right now. Don't go if you're ill, but if you want to know if you have antibodies from disease or vaccination, they cease testing donors' blood June 25...

American Red Cross
COVID-19 Antibody Testing Ending Soon

For a few more weeks, all American Red Cross blood donations are being tested for COVID-19 antibodies. Results may show an immune response developed after your vaccination or past exposure to this coronavirus. To learn more about your body’s immune response through Red Cross antibody testing, donate blood, platelets or plasma before June 25, 2021...

https://www.redcrossblood.org/donate-blood/dlp/covid-19-antibody-testing.html

>38 margd: My original CDC card lives inside my passport, and the laminated photocopy of it lives in my (larger) wallet. The records of vaccination are also available digitally through the online portal of the provider network that administered them. Best I can do. Fortunately, they haven't been officially relevant, but if the US-UK vaxx travel corridor ever becomes a reality, who knows how that will work?

Also: very glad to have the Pfizer onboard given I'm presently in Scotland and out of quarantine.

>42 davidgn: Scotland--you lucky dog! The Cdn border is still closed ... Gov Inslee had some practical suggestions on how to approach reopening. Another wrench: Cdn border guards are voting this week on possible strike...AARGH!!

Gov Jay Inslee, State of Washington, wrote secretaries of US State and Homeland Security (June 4)
requesting that the US & Cdn governments work to find innovative ways to reopen the border consistent with public health guidance,
e.g., begin by prioritizing groups such as property owners, families, a US peninsula surrounded by Canada.

"Specific actions that would be responsive to the needs of these groups and promote border efficiency include:
• A binational approach that uses the NEXUS program as a way for travelers to voluntarily share vaccine records electronically with both the US and Canada.
• Using the ArriveCAN platform that is required for entry into Canada to share vaccine records and/or negative test results."

https://www.governor.wa.gov/sites/default/files/Gov%20Border%20Letter%20to%20Bli...
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A wrench in reopening? (June 12, 2021)

Possibly jeopardizing reopening plans is news that a union representing 9,000 Canadian Border Service Agency workers is planning to begin voting next week on a possible strike, the CBC reported Friday.

The Public Service Alliance of Canada says that 5,500 border officers, 2,000 headquarters staff and other workers at Canada Post facilities have been without a contract for nearly three years and will begin taking a vote on whether to strike beginning June 16, CBC reported.

The union told the CBC they are seeking better protections for staff to address a “toxic” workplace and that they seek conditions similar to that of other law enforcement workers in Canada.

A strike by border officers could impact the ability of travelers — both essential and non-essential — to enter Canada.

https://www.bellinghamherald.com/news/coronavirus/article252056613.html

Isaac Bogoch (infectious disease MD) @BogochIsaac | 5:22 PM · Jun 15, 2021·Twitter Web App
Most regions of the world are seeing a decline in #COVID19 burden, except Africa. (margd: and se Asia)
In the last 7 days the African continent has seen a 44% increase in cases & 20% increase in deaths.
We need a major push to boost support for global vaccine equity (e.g. the COVAX program).

Quote Tweet
Maria Van Kerkhove (WHO infectious disease) @mvankerkhove · 1h
NEW WHO weekly epidemiological situation report
Global trends are declining, but great variability by region, country, & within countries
Latest on cases, deaths, circulation of 4 VOCs, plus info on newly classified VOI Lambda (C.37)

Soon here:
https://who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
Image: graph--cases by region ( https://twitter.com/mvankerkhove/status/1404909441288478720/photo/1 )
Image: table--cases & deaths by region ( https://twitter.com/mvankerkhove/status/1404909441288478720/photo/2 )
Image: table--variants of concern & interest as of June 15
( https://twitter.com/mvankerkhove/status/1404909441288478720/photo/3 )
Image: maps reporting alpha, beta, delta, gamma ( https://twitter.com/mvankerkhove/status/1404909441288478720/photo/4 )

>42 davidgn:

My vaccination status certificate lives in a database in the Kenyan Ministry of Health. It's available online and it has one of those square bar code thingies so it can be electronically verified. Same with COVID tests that one has to do if one travels abroad. When I flew into South Sudan last week they didn't have the capacity to scan the bar code but they insisted on seeing a soft copy as well as the hard copy that I had printed out.

I may apply for a NEXUS card. Intent of NEXUS card was to allow fast passage across US-Cdn border, so I assume the two countries will incorporate vaxx info somehow. In past we usually could time our crossing to avoid long line-ups, so never needed the cards. Wait times could be long in future, though, if border guards need to check each person's COVID and vaxx status without some kind of support.

Newsom says vaccine verification is coming in California, but 'it's not a passport'
Here are the details known so far about the plan, expected as early as this week
Kellie Hwang | June 15, 2021

...The Biden administration has said it will not develop a federal vaccine passport system, but allow the private sector or local jurisdictions to develop verification systems or require proof of vaccination at their own discretion.

...Some states, including Florida and Texas, have placed bans or limits on vaccination certificates, such as prohibiting their issuance or use, forbidding businesses or government from requiring them, or barring mandatory use by individuals. Most neither forbid nor require them.

...(CA Gov Newsom said,) “It’s not a passport, it’s not a requirement, it’s just the ability now to have an electronic version of that paper version, so you’ll hear more about that in the next couple of days,” ... the system would essentially provide people with an electronic version of their vaccine cards.

...Among U.S. states, only New York and Hawaii have implemented verification programs. New York’s voluntary program allows businesses to scan a QR code on smartphones that verify full vaccination or a recent negative COVID-19 test.

In Hawaii, the state has an inter-island passport program that allows residents to skip testing and quarantine requirements if they are traveling to another island. Domestic travelers can skip quarantine if they get tested at a “trusted partner” site. When the state reaches 60% immunization, it will lift pre-testing and quarantine requirements for domestic travelers who are vaccinated and upload their status to the Safe Travels website.

...Israel introduced an internal program called the Green Pass in February, allowing fully vaccinated citizens into certain places and events.

The European Union recently endorsed a new electronic vaccination travel certificate allowing people to travel between European countries without quarantine or extra testing. It will be recognized by all 27 member nations starting July 1, and several countries have already started using it. Travelers will receive their passes from their own country, not from a centralized European system.

https://www.sfchronicle.com/local/article/Newsom-says-vaccine-verification-is-co...

Razzaghi H, Meghani M, Pingali C, et al. COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy — Eight Integrated Health Care Organizations, United States, December 14, 2020–May 8, 2021. MMWR Morb Mortal Wkly Rep. ePub: 15 June 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7024e2external icon https://www.cdc.gov/mmwr/volumes/70/wr/mm7024e2.htm

Summary
...What is added by this report?
As of May 8, 2021, 16.3% of (135,968) pregnant women identified in CDC’s Vaccine Safety Datalink (VSD) had received 1 or more dose of a COVID-19 vaccine during pregnancy in the United States. Vaccination was lowest among Hispanic (11.9%) and non-Hispanic Black women (6.0%) and women aged 18–24 years (5.5%) and highest among non-Hispanic Asian women (24.7%) and women aged 35–49 years (22.7%).

What are the implications for public health practice?
Improving outreach to and engagement with health care providers and pregnant women, especially those who are younger and from racial and ethnic minority groups, could increase vaccine confidence and thus coverage of COVID-19 vaccination in this population.

...analyses of emerging data regarding safety of COVID-19 vaccines, specifically mRNA vaccines, have detected no safety signals for pregnant women. In early data from three of CDC’s vaccine safety monitoring systems, no safety concerns were identified for vaccinated pregnant women or their infants; additional follow-up is needed, particularly among women vaccinated in the first and second trimesters of pregnancy... There are also emerging data suggesting that COVID-19 vaccination during pregnancy can lead to transfer of antibodies through placenta and breast milk, which might confer some immunity to newborns.

...Although low, COVID-19 vaccination coverage among pregnant women is expected to increase as vaccine availability and access improve, and as more safety data become available. Addressing barriers to access as well as augmenting the scientific evidence regarding safety and effectiveness of COVID-19 vaccines in pregnancy are critical. In addition, vaccine misinformation and hesitancy should be addressed. Strategies and approaches to expanding vaccination coverage in ways to ensure and prioritize equity also should be implemented. Finally, making accurate and timely information available to health care providers and pregnant women could increase confidence and thus acceptance of COVID-19 vaccines in this population.

Headache and runny nose linked to Delta variant
June 14, 2021

A headache, sore throat and runny nose are now the most commonly reported symptoms linked to Covid infection in the UK, researchers say.

Prof Tim Spector, who runs the Zoe Covid Symptom study,* says catching the Delta variant can feel "more like a bad cold" for younger people. (Delta variant, B.1.617.2 first identified in India now accounts for 90% of Covid cases in the UK.)

...Fever remains quite common but loss of smell no longer appears in the top 10 symptoms, Prof Spector says. "This variant seems to be working slightly differently...People might think they've just got some sort of seasonal cold and they still go out to parties and they might spread around to six other people...We think this is fuelling a lot of the problem...The message here is that if you are young, you are going to get milder symptoms anyway...It might just feel like a bad cold or some funny 'off' feeling - but do stay at home and do get a test."...

https://www.bbc.com/news/health-57467051

* COVID Symptom Study
https://covid.joinzoe.com/us-2

Opinion: The delta variant is a rising threat in the U.S. We have to redouble vaccination efforts.
Ashish K. Jha (Dean, Brown U School of Public Health) | June 16, 2021

As we head into summer, the covid-19 pandemic in the United States looks increasingly different depending on where you are. But for those not fully vaccinated, it is becoming increasingly dangerous almost everywhere.

So far, 17 states and the District have reached President Biden’s goal of vaccinating 70 percent of adults with at least one shot...

Meanwhile, vaccination rates have flatlined in other states. In Tennessee, Wyoming, Mississippi, Idaho and a variety of states in between, the number of Americans stepping up to protect themselves and their communities has dwindled to a trickle. ...

With U.S. case numbers relatively low overall, masks disappearing and society reopening, it is not hard to imagine an end to the pandemic. But we must be clear: The pandemic is not over in the United States, nor can it end so long as covid-19 rages across the globe. The strongest evidence of the global pandemic’s influence on Americans’ lives recently arrived on our shores: the delta variant of the virus. It is a profoundly concerning threat.

...The emerging and relatively strong evidence is that delta is far more contagious than any other variant recorded to date. It appears to be more deadly to those infected, and it appears to cause more infections among people with immunity than many other variants.

... In India, the delta variant flattened the health-care system and caused hundreds of thousands of deaths. In Britain, it has quickly become the dominant strain and has caused the number of daily infections to triple in just the past month. ...As of Wednesday, the delta variant accounts for 10 percent of U.S. infections and is doubling its share of new cases every two weeks. At this rate, delta will become our dominant strain in the next month to six weeks.

For partly vaccinated Americans — those who have had just one shot of Pfizer or Moderna — the delta variant’s tendency to escape an immune response is a problem. While a single shot of these vaccines previously offered 80 to 85 percent protection (and two shots offered 95 percent), a single shot of Pfizer is only 33 percent effective against the delta variant. Thankfully, fully vaccinated individuals — that is, with two shots — get almost 90 percent protection. We don’t know how much immunity gained from prior infections alone will protect people, but it may not be enough.

...We are entering a time when being unvaccinated is going to become exceedingly more dangerous. Society is open. Distancing is a thing of the past, and mask-wearing is declining. All of the public health protections that kept unvaccinated people safe are disappearing, but the delta variant is gaining momentum. In some states, such as Mississippi and Wyoming, vaccination rates mean that covid cases are likely to spike this summer and fall. Even in highly vaccinated places, the delta variant may trigger the occasional outbreak. The difference will be in hospitalizations and deaths. For the vaccinated, breakthrough infections will be inconvenient, annoying or maybe even miserable. But rarely deadly. The unvaccinated will be far more vulnerable.

...We have to redouble efforts to get shots — two shots when needed — into arms here in the United States and across the globe.

https://www.washingtonpost.com/opinions/2021/06/16/delta-variant-ashish-jha-us-v...

Study details the treatment of COVID-19 vaccine-associated myocarditis-like illness in 7 patients
American Heart Accociation | June 17, 2021

...“The clinical course of vaccine-associated myocarditis-like illness appears favorable, with resolution of symptoms in all patients. Given the potential morbidity of COVID-19 infection even in younger adults, the risk-benefit decision for vaccination remains highly favorable. Vaccine adverse event reporting remains of high importance and further studies are needed to elucidate the pathophysiological mechanism to potentially identify or prevent future occurrences,” said the researchers.

...According to the CDC, fewer than 1,000 cases of myocarditis-like illnesses were reported as of May 31, 2021, and nearly 312 million doses of COVID-19 vaccines have been administered in the U.S. to-date.

The CDC is holding a special meeting on Friday, June 18 to review the evidence of cases of suspected myocarditis developing in some patients after receiving the COVID-19 vaccine, as reported to the Vaccine Adverse Event Reporting System. The Association’s science leaders are attending the meeting for further developments.

https://www.news-medical.net/news/20210617/Study-details-the-treatment-of-COVID-...

--------------------------------------------
Rosner, C. M., et al. (2021) Myocarditis Temporally Associated with COVID-19 Vaccination. Circulation. doi.org/10.1161/CIRCULATIONAHA.121.055891. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055891

A Pill to Treat Covid-19? The U.S. Is Betting on It.
A new $3.2 billion program will support the development of antiviral pills, which could start arriving by the end of this year.
Carl Zimmer | June 17, 2021

The U.S. government spent more than $18 billion last year funding drugmakers to make a Covid vaccine, an effort that led to at least five highly effective shots in record time. Now it’s pouring more than $3 billion on a neglected area of research: developing pills to fight the virus early in the course of infection, potentially saving many lives in the years to come.

The new program, announced on Thursday by the Department of Health and Human Services, will speed up the clinical trials of a few promising drug candidates. If all goes well, some of those first pills could be ready by the end of the year. The Antiviral Program for Pandemics will also support research on entirely new drugs — not just for the coronavirus, but for viruses that could cause future pandemics.

A number of other viruses, including influenza, H.I.V. and hepatitis C, can be treated with a simple pill. But despite more than a year of research, no such pill exists to treat someone with a coronavirus infection before it wreaks havoc. Operation Warp Speed, the Trump administration’s program for accelerating Covid-19 research, invested far more money in the development of vaccines than of treatments, a gap that the new program will try to fill.

Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and a key backer of the program, said he looked forward to a time when Covid-19 patients could pick up antiviral pills from a pharmacy as soon as they tested positive for the coronavirus or develop Covid-19 symptoms...

https://www.nytimes.com/2021/06/17/health/covid-pill-antiviral.html
______________________________________________________

Eric Topol @EricTopol | 6:03 PM · Jun 17, 2021:
...Well, there's already an inhaled ACE2 nanodecoy that worked in macaques to prevent covid...
https://nature.com/articles/s41565-021-00923-2

Eric Feigl-Ding @DrEricDing | 5:08 PM · Jun 17, 2021
https://twitter.com/DrEricDing/status/1405634361949671429

Confirmed—#DeltaVariant is by far the *most contagious** variant found to date, with a transmissibility that is ~2x faster than older strain. #P1 is 2nd fastest, says WHO study.Thread
B117 #Alpha—29% faster (first reported in UK)
B1351 #Beta—25% (first reported in S Africa)
P1 #Gamma—38% (first reported in Brazil)
B16172 #Delta—97% (first reported in India)
Image ( https://twitter.com/DrEricDing/status/1405633531695489027/photo/1 )

2) “Effective reproduction number of SARS-CoV-2 variants of concern/interest
compared against each other, 64 countries, data until 3 June 2021”
https://eurosurveillance.org/content/10.280
Image ( https://twitter.com/DrEricDing/status/1405634361949671429/photo/1 )

Scott Gottlieb, MD (frmr FDA) @ScottGottliebMD | 6:34 PM · Jun 17, 2021:
A well done study evaluating potential nervous system effects of COVID19 based on brain scans
finds "significant, deleterious impact" on certain parts of the brain -
perhaps pointing to a microvascular effect of virus on certain regions of nervous system?
https://medrxiv.org/content/10.1101/2021.06.11.21258690v1.full.pdf *
Image-text excerpt ( https://twitter.com/ScottGottliebMD/status/1405654990128046083/photo/1 )
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* Gwenaëlle Douaud et al. 2021. Brain imaging before and after COVID-19 in UK Biobank. MedRxiv (June 15, 2021) 32 p. https://doi.org/10.1101/2021.06.11.21258690 https://medrxiv.org/content/10.1101/2021.06.11.21258690v1.full.pdf

Preprint. Not yet reviewed.

Abstract
There is strong evidence for brain-related pathologies in COVID-19, some of which could be a consequence of viral neurotropism. The vast majority of brain imaging studies so far have focused on qualitative, gross pathology of moderate to severe cases, often carried out on hospitalised patients. It remains unknown however whether the impact of COVID-19 can be detected in milder cases, in a quantitative and automated manner, and whether this can reveal a possible mechanism for the spread of the disease. UK Biobank scanned over 40,000 participants before the start of the COVID-19 pandemic, making it possible to invite back in 2021 hundreds of previously-imaged participants for a second imaging visit. Here, we studied the effects of the disease in the brain using multimodal data from 782 participants from the UK Biobank COVID-19 re-imaging study, with 394 participants having tested positive for SARS-CoV-2 infection between their two scans. We used structural and functional brain scans from before and after infection, to compare longitudinal brain changes between these 394 COVID-19 patients and 388 controls who were matched for age, sex, ethnicity and interval between scans. We identified significant effects of COVID-19 in the brain with a loss of grey matter in the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula. When looking over the entire cortical surface, these results extended to the anterior cingulate cortex, supramarginal gyrus and temporal pole. We further compared COVID-19 patients who had been hospitalised (n=15) with those who had not (n=379),and while results were not significant, we found comparatively similar findings to the COVID-19vs control group comparison, with, in addition, a greater loss of grey matter in the cingulate cortex, central nucleus of the amygdala and hippocampal cornu ammonis... Our findings thus consistently relate to loss of grey matter in limbic cortical areas directly linked to the primary olfactory and gustatory system. Unlike in post hoc disease studies, the availability of pre-infection imaging data helps avoid the danger of pre-existing risk factors or clinical conditions being mis-interpreted as disease effects. Since a possible entry point of the virus to the central nervous system might be via the olfactory mucosa and the olfactory bulb, these brain imaging results might be the in vivo hallmark of the spread of the disease (or the virus itself) via olfactory and gustatory pathways.

...DISCUSSION
...the thalamus of the participants who will later contract COVID-19appears to already differ from the controls years before infection... Whether these differences played a subsequent role in those patients being more likely to contract the virus, or to develop symptoms from them,would need to be investigated further ..

...The limbic nature of the regions of the olfactory system, and their physical proximity to the hippocampus in particular, raise the possibility that longer-term consequences of SARS-CoV-2 infection (for which some suggest that the coronavirus itself enters the brain via the olfactory route) might in time contribute to Alzheimer’s disease or other forms of dementia...

...This is the first longitudinal imaging study comparing brain scans acquired from individuals before and after SARS-CoV-2infection to thosescansfrom a well-matchedcontrol group. It alsois one of the largest COVID-19 brain imaging studies, with 782participants including394 individuals with COVID-19. Itsunique designmakes it possible to tease apart the contribution of the disease from pre-existing risk factors. By using automated, objectiveand quantitative methods, we were able to uncover a consistent spatial pattern of loss of grey matter in limbic brain regions forming an olfactory and gustatory network.Whether these abnormal changes are the hallmarkof the spread of the disease (or the virus itself)in the brain, which mayprefigure a future vulnerability of the limbic system, including memory, for these patients, remainsto be investigated

INDONESIA

Eric Topol @EricTopol | 9:42 AM · Jun 18, 2021:
The Delta variant is causing covid cases and hospitalizations to go vertical in Indonesia
https://wsj.com/articles/rising-covid-19-cases-threaten-indonesia-with-a-deadly-... by @JonathanEmont

"Approximately 400 medical workers who were infected had been fully vaccinated with Sinovac’s shot"
That vaccine has not been studies w/ B.1.617.2
Image-graph Indonesia cases thru June 18, 2021 ( https://twitter.com/EricTopol/status/1405883685606354945/photo/1 )
Image-photo 1st p WSJ article ( https://twitter.com/EricTopol/status/1405883685606354945/photo/2 )

Boy hamsters will be reconsidering their vaccine hesitancy?

COVID-19 Can Infect Testes; Evidence of Direct Infection In Organ By Coronavirus Found (Study)
According to researchers from the University of Texas Medical Branch, the SARS-CoV-2 coronavirus was found to infect the testes in an animal model, thereby, offering evidence of direct infection of the male reproductive organ by COVID-19.
Jeevan Biswas | June 19, 2021

https://www.ibtimes.co.in/covid-19-can-infect-testes-evidence-direct-infection-o...

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Rafael K. Campos et al. 2021. SARS-CoV-2 Infects Hamster Testes. Microorganisms 2021, 9(6), 1318; https://doi.org/10.3390/microorganisms9061318 (Published: 17 June 2021) https://www.mdpi.com/2076-2607/9/6/1318/htm

Abstract
The COVID-19 pandemic continues to affect millions of people worldwide. Although SARS-CoV-2 is a respiratory virus, there is growing concern that the disease could cause damage and pathology outside the lungs, including in the genital tract. Studies suggest that SARS-CoV-2 infection can damage the testes and reduce testosterone levels, but the underlying mechanisms are unknown and evidence of virus replication in testicular cells is lacking. We infected golden Syrian hamsters intranasally, a model for mild human COVID-19, and detected viral RNA in testes samples without histopathological changes up to one month post-infection. Using an ex vivo infection model, we detected SARS-CoV-2 replication in hamster testicular cells. Taken together, our data raise the possibility that testes damage observed in severe cases of COVID-19 could be partly explained by direct SARS-CoV-2 infection of the testicular cells.

Sounds like increasing reason to protect unvaxxed kids' brains, especially but not exclusively, from COVID...
See thread for images, comments: https://twitter.com/dgurdasani1/status/1406726553690595332

Deepti Gurdasani (Epidemiology, Queen Mary U of London) @dgurdasani1 | 5:32 PM · Jun 20, 2021

More & more evidence accruing that SARS-CoV-2 causes significant persistent effects on the brain. We now have multiple strands supporting this-
-long-term symptoms-brain fog, memory loss
-higher risk of stroke/neuro diseases
-structural brain changes
-virus persistence in brain

We know that SARS-CoV-2 is neuro-invasive. This means that it enters the brain- we think this is through the olfactory nerve (the nerve that helps us smell) through the nose. This has been shown in mice, hamsters and directly in humans in autopsies.
https://nature.com/articles/s41593-020-00758-5
Image ( https://twitter.com/dgurdasani1/status/1406726560191856641/photo/1 )

Replicating SARS-CoV-2 has also been shown to persist in neuro-epithelium (olfactory nerves in the nose) for up to 6 months among people who have recurrent or persistent loss of smell.

COVID-19–related anosmia is associated with viral persistence and inflammation in human olfactory...
Patients with COVID-19 can develop loss of smell and/or taste. Unfortunately, the pathophysiology of these alterations remains unclear. Here, de Melo et al. examined the olfactory mucosa in patients...
https://stm.sciencemag.org/content/13/596/eabf8396

Neurological symptoms are significant among people post-COVID, & they persist for long periods of time, even after other symptoms recover. ONS data shows that problems with concentration, memory, brain fog, loss of smell/taste are common persistent symptoms after infection
Image ( https://twitter.com/dgurdasani1/status/1406726568983019536/photo/1 )

Symptom based surveys have consistently shown that neurological symptoms are more likely to arise later, and persist over time, and symptom clusters that have neurological symptoms generally also correlate with poorer day to day functioning.
Image ( https://twitter.com/dgurdasani1/status/1406726575488372742/photo/1 )

A @TheLancetPsych study showed that neurological & psychiatric diagnosis were very common at 6 months after COVID-19, and the risk for psychiatric disorders, strokes, dementia, muscle disorders was significantly higher, even in those not hospitalised.

Important study out from @TheLancetPsych on neurological & psychiatric manifestations across 236,379 people with 6 months follow up after COVID-19 in the US- examined using electronic health records.

What did it find?
https://thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00084-5/fulltext?...

There have been earlier studies that have looked at cognitive decline following hospitalisation with COVID-19 suggesting significant reduction after hospitalisation. These studies have been limited by not having measurements pre-COVID-19 to establish that this was the cause.

This is addressed now in a study within UK biobank. This is a cohort of generally healthy people who have had many measurements done as part of the study. ~40,000 people have had brain imaging done for research purposes before the COVID-19 pandemic.

Replicating SARS-CoV-2 has also been shown to persist in neuro-epithelium (olfactory nerves in the nose) for up to 6 months among people who have recurrent or persistent loss of smell.

COVID-19–related anosmia is associated with viral persistence and inflammation in human olfactory...
Patients with COVID-19 can develop loss of smell and/or taste. Unfortunately, the pathophysiology of these alterations remains unclear. Here, de Melo et al. examined the olfactory mucosa in patients...
stm.sciencemag.org

Neurological symptoms are significant among people post-COVID, & they persist for long periods of time, even after other symptoms recover. ONS data shows that problems with concentration, memory, brain fog, loss of smell/taste are common persistent symptoms after infection
Image ( https://twitter.com/dgurdasani1/status/1406726598313787394 )

Symptom based surveys have consistently shown that neurological symptoms are more likely to arise later, and persist over time, and symptom clusters that have neurological symptoms generally also correlate with poorer day to day functioning.
Image

A @TheLancetPsych study showed that neurological & psychiatric diagnosis were very common at 6 months after COVID-19, and the risk for psychiatric disorders, strokes, dementia, muscle disorders was significantly higher, even in those not hospitalised.

Important study out from @TheLancetPsych on neurological & psychiatric manifestations across 236,379 people with 6 months follow up after COVID-19 in the US- examined using electronic health records.

What did it find?
https://thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00084-5/fulltext?...

There have been earlier studies that have looked at cognitive decline following hospitalisation with COVID-19 suggesting significant reduction after hospitalisation. These studies have been limited by not having measurements pre-COVID-19 to establish that this was the cause.

This is addressed now in a study within UK biobank. This is a cohort of generally healthy people who have had many measurements done as part of the study. ~40,000 people have had brain imaging done for research purposes before the COVID-19 pandemic.

Of the people who have had their second MRI brain scan in the Biobank study, some of them developed COVID-19 before the second scan. We can compare brain changes between those infected vs not infected by comparing the change in brain structure between the two scans.

394 people who were COVID-19 positive (only 15 of these were hospitalised) were imaged after COVID-19 was diagnosed. These were compared with 388 controls (not diagnosed with COVID-19). Both groups had MRI scans done before the pandemic at baseline.

They were compared for volume and thickness in certain areas of the brain. Cases & controls were matched for age, sex, ethnicity & the time between the baseline and repeat MRI scan to ensure any difference in change in brain structure between the two groups was not down to these.

The groups were well matched. Age was between 47-80 (mean age ~59). Similar blood pressure, prevalence of diabetes and BMI. As mentioned, most of the COVID group was people who were infected & tested in the community with non-severe COVID-19.
Image ( https://twitter.com/dgurdasani1/status/1406726592794083329/photo/1 )

Most of the patients had been diagnosed Oct 2020 or after, and the duration between infection and scan varied accordingly. Mean duration was 4.5 months post COVID-19
Image ( https://twitter.com/dgurdasani1/status/1406726598313787394/photo/1 )

The study found significant reduction in grey matter in certain parts of the brain- especially those associated with smell, and memory. Of note- these are changes in a population of people who mostly had mild COVID symptoms - *greater* reduction from baseline in those with COVID
Image ( https://twitter.com/dgurdasani1/status/1406726603967762434/photo/1 )

While correlation isn't causation, the fact that these people were imaged at baseline before COVID-19 - allowing to compare to a group not infected with COVID-19 to look at difference in decline in grey matter after COVID compared to those who weren't infected makes it strong.

Remember, these groups were also the same age, had the same interval between scans, and many similar characteristics, making it unlikely this decline is down to something other than COVID-19

This is very concerning- we are seeing evidence of significant changes in the brain even among people with relatively mild COVID-19. This study was in 46-80 yr olds, and many would've been healthy. We urgently need to understand the impact of COVID-19 in younger age groups too.

This isn't just one study that suggests a link between SARS-CoV-2 and neurodegenerative disease. There have been several care reports of early-onset parkinsonism after SARS-CoV-2 infection, highlighting possible links with neuro-degenerative disease.
SARS-CoV-2 and the risk of Parkinson's disease: facts and fantasy

During the pandemic it has become clear that severe acure respiratory syndrome coronavirus (SARS-CoV-2) causes not just respiratory disease, but can affect multiple organs and tissues. Of note is the...
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30442-7/fullt...

Does this happen with other viruses?
Yes, many viruses invade and affect the brain: herpes viruses, Zika virus, measles, polio and of course, Spanish flu (encephalitis lethargica as immortalised in Awakenings). Other coronaviruses are known to invade the brain too.

This has been concerning for a while, but recent reports show us ignoring this will come at a huge cost. We need to stop focusing on hospitalisations & deaths as the only outcome, thinking that it's ok for transmission to continue at such levels. It's not.

This is the sort of thinking that will possibly leave thousands with chronic debilitating neurological illness, as well as other impacts of long COVID. By the time our scientific community & govt are satisfied that there is irrevocable evidence, it'll be much too late.

While I'm not a neuroscientist, I've worked with @HZiauddeen, who is, to make sure my interpretation of the UK biobank study is correct. I've seen several non-experts comment on possible limitations of the study, so wanted to ensure that I'd sought an expert perspective.

Conclusion: This is a robust study that shows significant change in brain structure, and thinning of grey matter in memory, smell and taste associated brain regions post-COVID-19. We should be concerned. This is not a virus we should be happy to expose anyone to.

Link to UK Biobank study here:
https://medrxiv.org/content/10.110

Norway: "52% of home-isolated young adults, aged 16–30 years, had symptoms at 6 months" (!!)

Eric Topol @EricTopol | 8:39 AM · Jun 23, 2021:
Just published @NatureMedicine
A prospective cohort with #LongCovid, mostly initially with mild illness, but
at 6 months majority had debilitating symptoms, including breathing and cognitive difficulties.
Higher neutralizing antibodies notable.

https://nature.com/articles/s41591-021-01433-3 *
Image-p 1 highlighted ( https://twitter.com/EricTopol/status/1407679605163450375/photo/1 )
Image-graphic ( https://twitter.com/EricTopol/status/1407679605163450375/photo/2 )

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* Bjørn Blomberg et al. 2021. Long COVID in a prospective cohort of home-isolated patients. Nature Medicine (June 23, 2021). https://www.nature.com/articles/s41591-021-01433-3

Abstract
Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that

52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including
loss of taste and/or smell (28%, 17/61),
fatigue (21%, 13/61),
dyspnea--shortness of breath--(13%, 8/61),
impaired concentration (13%, 8/61) and
memory problems (11%, 7/61).

Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

...Results
The median age of the study population was 46 years (interquartile range (IQR) 30–58 years) with 51%...women. Forty-four percent had comorbidities..., the most frequent being chronic lung disease (12%..., 34/312 with asthma), hypertension (11%...), chronic heart disease (7%...), rheumatic diseases (6%...), diabetes (4%...) and immunosuppressive conditions (4%...)...

...Increased antibody titers as well as pre-existing lung disease were independently associated with both persistent fatigue and total number of symptoms at 6 months in multivariable analysis (Table 4 and Fig. 2c,d,g,h). Severity of initial illness was associated with persistent fatigue and weakly associated with total number of symptoms (Table 4)...

Eric Topol @EricTopol | 9:21 AM · Jun 23, 2021:
The situation in Africa is worsening, a "3rd wave" is starting, multiple countries are affected by the Delta variant

https://nytimes.com/2021/06/22/world/africa/africa-covid-crisis-variants.html by @Lattif
Image- highlighted photo of article ( https://twitter.com/EricTopol/status/1407690225531248640/photo/1 )
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Africa’s third wave: ‘What haunts me a lot is the Indian scenario’
Joseph Cotterill in Johannesburg, David Pilling and Andres Schipani in Addis Ababa | 6/23/2021

African countries from Uganda to South Africa are buckling under a ferocious third wave of coronavirus infections as the continent falls far behind the rest of the world in vaccinations.

The rolling seven-day average of new African cases rose to about 25,000 a day last week from 7,000 in the middle of May, according to data from Africa’s Centres for Disease Control and Prevention.

Doctors have warned of dwindling hospital beds and oxygen supplies as more than a dozen nations are reporting their worst levels of infection since the pandemic began, just as they are struggling to launch mass rollouts of vaccines.

“We are not winning for sure. Each time you get a wave the peak is worse than the previous one,” said John Nkengasong, director of Africa’s CDC.

https://ft.com/content/af162963-078c-4c63-9731-e4c8d5e5de2a by @jsphctrl @AndresSchipani

Image- Johns Hopkins graph, Mar 2020 - June 2021 ( https://twitter.com/EricTopol/status/1407690225531248640/photo/2 )

J&J protective in macaques against B.1.351 (Beta, S Africa), though somewhat less so than WA1/2020 (Alpha, Washington State)

Eric Topol @EricTopol | 10:09 AM · Jun 23, 2021:
Just out Nature

Evidence of both neutralizing antibody and T cell protection with the J&J vaccine against the Beta (B.1.351) variant, which has distinctive immune evasion features, in the macaque model

Image-antibody titer J&J v WA, UK, Indian variants ( https://twitter.com/EricTopol/status/1407702322289942532/photo/1 )
Image-T cells J&J v variants of concern ( https://twitter.com/EricTopol/status/1407702322289942532/photo/2 )

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Jingyou Yu et al. 2021. Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques. Nature (23 June 2021) https://nature.com/articles/s41586-021-03732-8

Accepted, unedited manuscript.

Abstract
The emergence of SARS-CoV-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current COVID-19 vaccines... The Ad26.COV2.S vaccine expresses a stabilized Spike protein from the WA1/2020 strain and has recently demonstrated protective efficacy against symptomatic COVID-19 in humans in multiple geographic regions, including in South Africa where 95% of sequenced viruses in COVID-19 cases were the B.1.351 variant... Here we show that Ad26.COV2.S elicits humoral and cellular immune responses that cross-react with the B.1.351 variant and protects against B.1.351 challenge in rhesus macaques. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 as compared with WA1/2020 but elicited CD8 and CD4 T cell responses that were comparable against WA1/2020, B.1.351, B.1.1.7, P.1, and CAL.20C variants. B.1.351 infection of sham control rhesus macaques resulted in higher levels of virus replication in bronchoalveolar lavage and nasal swabs than did WA1/2020 infection. Ad26.COV2.S provided robust protection against both WA1/2020 and B.1.351, although we observed higher levels of virus in vaccinated animals following B.1.351 challenge. These data demonstrate that Ad26.COV2.S provided robust protection against B.1.351 challenge in rhesus macaques. Our findings have important implications for vaccine control of SARS-CoV-2 variants of concern.

September/Delta is coming and US immunity wall is insufficient...

Eric Topol @EricTopol | 8:47 AM · Jun 23, 2021:
The Delta variant's impact in the US could be largely mitigated if we had built an immunity wall with higher vaccination levels.
Time is running out.

https://newyorker.com/science/medical-dispatch/the-delta-variant-is-a-grave-dang...
NewYorker by @DhruvKhullar w/ @angie_rasmussen
Image-excerpt of article ( https://twitter.com/EricTopol/status/1407681838827466752/photo/1 )

While the Delta variant case frequency for US infections is ~20% overall by @CDCgov, there's marked heterogeneity among states
https://ft.com/content/730e35fd-9f9e-438b-8617-c0f1bc163fd3
by @nikasgari and @jburnmurdoch (FT estimates Delta prevalence much higher 37-42%)
Image-modeled incidence Delta in 14 states, Jan 1-June 18 ( https://twitter.com/EricTopol/status/1407560407078772743/photo/1 )

The lack of full licensure by @US_FDA for vaccines, despite having had 7 months to do plant inspections and review the BLA applications iteratively as they were submitted by sections, is holding us back in a major way. Yes, a BFD.
Image-photo of quote from article ( https://twitter.com/EricTopol/status/1407706367436070914/photo/1 )

Benjamin Alvarez (DW News) @BenjAlvarez1 | 6:35 PM · Jun 22, 2021
This #COVID19 vaccine animation
0:58 ( https://twitter.com/BenjAlvarez1/status/1407467294545035268 )

Source: https://www.bilibili.com/video/BV1i64y167av

Eric Topol @EricTopol | 5:01 PM · Jun 23, 2021
Important new and encouraging data for 3-vaccine doses (of messenger RNA vaccine BNT162b2 (Pfizer–BioNTech))
in more than 100 immuno-compromised people with solid organ transplants @NEJM
Image-antibodies after 1-3 doses ( https://twitter.com/EricTopol/status/1407806082441879554/photo/1 )

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Nassim Kamar et al. 2021. Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients (Correspondence). NEJM (June 23, 2021) DOI: 10.1056/NEJMc2108861 https://www.nejm.org/doi/full/10.1056/NEJMc2108861?query=featured_home

...This study showed that administration of a third dose of the BNT162b2 vaccine to solid-organ transplant recipients significantly improved the immunogenicity of the vaccine, with no cases of Covid-19 reported in any of the patients. However, a large proportion of the patients remain at risk for Covid-19. Barrier measures should be maintained, and vaccination of the relatives of these patients should be encouraged.

Ashish K. Jha, MD, MPH (Brown U)@ashishkjha | 5:30 PM · Jun 23, 2021:
CDC's advisory committee met today They examined data assess the risk and benefits of vaccines in young adults
And concluded that the benefits of these vaccines far outweigh the risks they may pose
Here's the key slide for 18 to 24 year-olds
Image ( https://twitter.com/ashishkjha/status/1407813247575728133/photo/1 )

AFRICA

Dr. Tom Frieden (frmer CDC director) @DrTomFrieden | 5:32 PM · Jun 23, 2021:
Deeply disturbed about rapid case increases in many countries in Africa. Delta and other variants. Limited health care capacity. Fragile health status. Potential nightmare scenario. 1/3

Immediate: Mask, limit super spreading, protect health care workers and health care systems and continue core health care services, reduce case fatality rates, double down on social protections including food, security, and more. Communicate honestly and openly. Build trust. 2/3

ASAP: Redistribute vaccine NOW to protect health care workers and the elderly, especially - but this won't protect soon enough, so masks, distancing irreplaceable in short term.

ASAP: Scale up vaccine manufacturing (anywhere). Governments should actively engage with industry.

Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children.

JE Schuster and A de St. Maurice. 2021. COVID-19 in Children—Not Just Little Adults (Invited Commentary). JAMA Netw Open. June 7, 2021;4(6):e2111441. doi:10.1001/jamanetworkopen.2021.11441 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780708

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Lyudmyla Kompaniyets, PhD et al. 2021. Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. JAMA Netw Open. June 7, 2021;4(6):e2111182. doi:10.1001/jamanetworkopen.2021.11182 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780706

Abstract

...Objective To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity....

Conclusions and Relevance This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19.

(See TABLE 3)

_____________________________________________________
Springfield Mercy treating infant with COVID-19;
what to watch for with your young child
Joe HickmanPublished: Jun. 24, 2021

...A tweet by Mercy’s Chief Administrative Officer Erik Frederick this week said that the hospital was caring for a less-than-one-year-old infant with COVID-19.

...“I don’t think they should be scared,” said Dr. Danyal Thaver, a Mercy Pediatric Critical Care Specialist, when asked his advice for anxious parents. “But at the same time I think they have to be vigilant enough to realize that COVID hasn’t gone away. Infants can get COVID and there have been cases of some dying from it. It’s rare, but it’s possible.”

...“The kids who are at a higher risk to get severe symptoms are kids under the age of one,” Thaver explained. “Or kids who have underlying medical conditions. Kids who have asthma, diabetes, a congenital heart problem or any kind of condition that makes their immune systems weak.”

Thaver pointed out that other respiratory illnesses normally associated with the fall or winter months are going around now as well.

So what should you be watching for as signs of COVID-19 or other respiratory illnesses in your infant?

“Trouble breathing or gasping for air,” Thaver said. “Not drinking or eating with a danger of getting dehydrated. A good way to assess that in infants is to see if they’re not making as many wet diapers as they normally would. Other things would be discoloration of the fingertips or nose or the lips. That can be a sign that they’re not getting enough oxygen. And if their brain is not getting enough oxygen they can be extremely irritable beyond being consolable. They may look confused or be extremely tired and not be able to be woke up. All those signs are concerning and that’s when parents should seek medical attention.”

And since no vaccinations are available for children under 12, the onus is on the rest of us to protect them.

“It’s definitely important that people who are around these kids should get the vaccine,” Thaver pointed out. “Because it’s not only going to protect them but also potentially (protect) that child who is more likely to get a severe illness if they catch COVID.”

https://www.ky3.com/2021/06/24/springfield-mercy-treating-infant-with-covid-19-w...

6 warning signs that the Delta variant is coming for unvaccinated Americans (unvaxxed everybody?)
Andrew Romano | June 25, 2021

Here are six warning signs that Delta is heading our way:
1. The U.K. has more immunity than the U.S. Cases and hospitalizations are increasing there anyway.
2. Once Delta lands somewhere — even somewhere with lots of immunity — it spreads fast.
3. To stay ahead of Delta, America’s vaccination rate should be increasing. It’s flatlining instead.
4. That leaves more than 100 million Americans largely defenseless against Delta — and they’re concentrated in places where the virus can still spread easily.
5. Delta will hospitalize and kill unvaccinated Americans, especially in undervaccinated communities. Just look at Missouri.
6. Meanwhile, vaccination is already saving Americans from Delta.

https://news.yahoo.com/6-warning-signs-that-the-delta-variant-is-coming-for-unva...

The Very First Case of COVID-19 Was Much Earlier Than We Knew, New Study Indicates
PETER DOCKRILL | 25 JUNE 2021

...New modeling of the outbreak proposes that the SARS-CoV-2 virus may have first begun infecting humans in China as early as October 2019, although mid-November is estimated to be the most likely timeframe.

That's significantly before the most widely accepted first case of the infection, which is early December 2019, based on an early assessment of patients with the novel coronavirus in Wuhan, China.

...In their study, the researchers repurposed a mathematical model from conservation science, called optimal linear estimation (OLE), which is traditionally used to infer species extinction dates based on their last reported sightings.

...the modeling suggests COVID-19 emerged in China well before December 2019, with the most probable first case occurring on November 17, although it could have been as early as October 4, the team suggests.

After taking hold in China, the virus then spread internationally, the researchers estimate, first to Japan on 3 January 2020, then Thailand on January 7, Spain on January 12, South Korea on January 14, and making it to the US on January 16.

The findings are reported in PLOS Pathogens.https://www.sciencealert.com/the-first-case-of-covid-19-was-much-earlier-than-records-show-study-suggests

Where Did the Coronavirus Come From? What We Already Know Is Troubling.
Zeynep Tufekci | June 25, 2021

...even if we are denied answers, we can still learn lessons.

... a better path forward is one of true global cooperation based on mutual benefit and reciprocity. Despite the current dissembling, we should assume that the Chinese government also doesn’t want to go through this again — especially given that SARS, too, started there.

This means putting the public interest before personal ambitions and acknowledging that despite the wonders of its power, biomedical research also holds dangers.

To do this, government officials and scientists need to look at the big picture: Seek comity and truth instead of just avoiding embarrassment. Develop a framework that goes beyond blaming China, since the issues raised are truly global. And realize that the next big thing can simply mean taking great care with a lot of small details.

https://www.nytimes.com/2021/06/25/opinion/coronavirus-lab.html

All (56,000) classrooms to have 2 air purifiers next year (Sept), New York City officials pledge
Pooja Salhotra and Amy Zimmer | June 23, 2021

...Already, the department has distributed 100,000 air purifiers to schools, and they are working to ensure each classroom has two air purifiers by the time schools fully reopen this fall. The air purifiers are high-efficiency particulate air filters, or HEPA filters, which lower the risk of exposure to the coronavirus. Ventilation has emerged as one of the most critical COVID prevention strategies, and HEPA filters are among the most efficient at capturing human-generated viral particles, according to the Centers for Disease Control and Prevention...

https://ny-chalkbeat-org.cdn.ampproject.org/c/s/ny.chalkbeat.org/platform/amp/20...

WHO urges fully vaccinated people to continue to wear masks as delta Covid variant spreads
Berkeley Lovelace Jr. | Jun 25 2021

The WHO urged fully vaccinated people to continue to wear masks and practice other Covid-19 pandemic safety measures as the highly contagious delta variant spreads rapidly across the globe.

...“Vaccine alone won’t stop community transmission,” (Dr. Mariangela Simao, WHO assistant director-general for access to medicines and health products) added. “People need to continue to use masks consistently, be in ventilated spaces, hand hygiene ... the physical distance, avoid crowding. This still continues to be extremely important, even if you’re vaccinated when you have a community transmission ongoing.”...

https://www.cnbc.com/2021/06/25/delta-who-urges-fully-vaccinated-people-to-conti...

Whereas most of the US is doing well, Nevada has joined Missouri in becoming the epicenter of the Delta variant hit.
Both states are now Delta dominant and have rising cases and hospitalizations (~50% and 20%, respectively, past 2 weeks)
Image-graph MO and NV ( https://twitter.com/EricTopol/status/1409186052334440452/photo/1 )

- Eric Topol @EricTopol | 12:25 PM · Jun 27, 2021

Gettings J, Czarnik M, Morris E, et al. Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools — Georgia, November 16–December 11, 2020. MMWR Morb Mortal Wkly Rep 2021;70:779–784. DOI: http://dx.doi.org/10.15585/mmwr.mm7021e1 https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e1.htm

Summary
...What is added by this report?
COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks and 39% lower in schools that improved ventilation. Ventilation strategies associated with lower school incidence included dilution methods alone (35% lower incidence) or in combination with filtration methods (48% lower incidence).

What are the implications for public health practice?
Mask requirements for teachers and staff members and improved ventilation are important strategies in addition to vaccination of teachers and staff members that elementary schools could implement as part of a multicomponent approach to provide safer, in-person learning environments.

...Discussion
...In schools that improved ventilation through dilution methods alone, COVID-19 incidence was 35% lower, whereas in schools that combined dilution methods with filtration, incidence was 48% lower. Ventilation can be improved in simple, cost-effective ways by keeping doors and windows open and using fans to increase air flow from open windows... In rooms that are difficult to ventilate or have an increased likelihood of being occupied by persons with COVID-19 (e.g., nurse’s office), installation of HEPA filters or UVGI should be considered.... However, only approximately one hal ...of school representatives reported being sure that ventilation was improved in school classrooms, and 18.0%...reported that their school implemented dilution methods in combination with filtration. These findings suggest that there are opportunities for many schools to reduce SARS-CoV-2 transmission through improved ventilation. Schools in lower-resourced communities might face barriers to installation of air filtration and purification devices; however, improvements can be made through dilution methods alone. CDC recommends improving ventilation through dilution, filtration, and purification methods, consistent with the school’s safety protocols...

Anatomy of a health conundrum: The racial gap in vaccinations
Akilah Johnson and Dan Keating | June 27, 2021

..The United States is awash in coronavirus vaccines, with free beer, plane tickets and million-dollar prizes dangled as inducements to persuade the reluctant to get a shot. Philadelphia is doling out $400,000 in giveaways. Despite that, a racial divide persists in the nation’s vaccination campaign, with federal figures showing counties with higher percentages of Black residents having some of the lowest vaccination rates in the country.

...The city of Philadelphia is the nation’s largest predominantly Black county, and it has one of the higher vaccination rates among counties with a preponderance of Black residents. But that doesn’t mean Black people are getting vaccinated at a high rate. The city’s data shows that while 52 percent of White people have received at least one dose of vaccine, just 34 percent of Black people have. Nationally, 54 percent of the population has received at least one dose...

https://www.washingtonpost.com/health/2021/06/27/why-black-americans-arent-being...

Scientist recovers coronavirus gene sequences secretly deleted last year in Wuhan
Jeanna Bryner | 6/23/2021

...The sequences don't tip the scales toward or away from one of the many theories about how SARS-CoV-2 came to be — they do not suggest the virus leaked from a high-security lab in Wuhan, nor do they suggest a natural spillover event. But they do firm up the idea that the novel coronavirus was circulating earlier than the first major outbreak at a seafood market.

..."There is no plausible scientific reason for the deletion: the sequences are perfectly concordant with the samples described in Wang et al. (2020a,b)," (esse Bloom of the Howard Hughes Medical Institute in Seattle) wrote in bioRxiv. "There are no corrections to the paper, the paper states human subjects approval was obtained, and the sequencing shows no evidence of plasmid or sample-to-sample contamination. It therefore seems likely the sequences were deleted to obscure their existence."

https://www.livescience.com/deleted-covid-19-gene-sequences-found.html
( Also: https://www.nytimes.com/2021/06/23/science/coronavirus-sequences.html )
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Jesse D. Bloom. 2021. Recovery of deleted deep sequencing data sheds morelight on the early Wuhan SARS-CoV-2 epidemic. BioRxiv (June 22, 2021) 11p. https://doi.org/10.1101/2021.06.18.449051 https://www.biorxiv.org/content/10.1101/2021.06.18.449051v1.full.pdf

Preprint. Not yet certified by peer review.

ABSTRACT
The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here I identify a data set containingSARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. Irecover the deleted files from the Google Cloud, and reconstruct partial sequences of 13 early epidemic viruses. Phylogeneticanalysis of these sequences in the context of carefully annotated existing data suggests that the Huanan Seafood Marketsequences that are the focus of the joint WHO-China report are not fully representative of the viruses in Wuhan early in theepidemic. Instead, the progenitor of known SARS-CoV-2 sequences likely contained three mutations relative to the marketviruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives....

(Heavily vaxxed) Israel to reinstate indoor mask mandate next week as COVID-19 cases keep rising
Virus czar Ash warns latest outbreak has spread to Kfar Saba, Ramla, Herzliya and other cities, pleads with public not to travel abroad, especially with unvaccinated children
TOI staff | 24 June 2021

...While a majority of adults in Israel have been vaccinated and the country has one of the highest inoculation rates in the world, (Coronavirus czar Nachman Ash) said the numbers were still far from the 80% figure he said would mark herd immunity...

https://www.timesofisrael.com/israel-to-reinstate-indoor-mask-mandate-next-week-...

___________________________________________________________

(Petition to US) CDC: Reinstate Indoor Mask Wearing Guidance

1. Reinstate mask-wearing guidance in indoor public places until cases of infection in the United States drops to almost zero, (maximum 1/100,000 positive tests in 7 days), and until a sufficient majority (70% at a minimum) of the U.S. population (adults + children) have been fully vaccinated...

2. Provide guidance (i.e. a common framework) for vaccine verification.

3. Advise the public to always carry a mask with them, even when outdoors.

4. Resume reporting all breakthrough infections.

https://www.endcoronavirus.org/blog/cdc-universal-mask-mandates

Pfizer and Moderna Vaccines Likely to Produce Lasting Immunity, Study Finds
Immune cells are still organizing to fight the coronavirus months after inoculation, scientists reported.
Apoorva Mandavilli | June 28, 2021

The vaccines made by Pfizer-BioNTech and Moderna set off a persistent immune reaction in the body that may protect against the coronavirus for years, scientists reported on Monday.

The findings add to growing evidence that most people immunized with the mRNA vaccines may not need boosters, so long as the virus and its variants do not evolve much beyond their current forms — which is not guaranteed. People who recovered from Covid-19 before being vaccinated may not need boosters even if the virus does make a significant transformation.

“It’s a good sign for how durable our immunity is from this vaccine,” said Ali Ellebedy, an immunologist at Washington University in St. Louis who led the study, which was published in the journal Nature...

https://www.nytimes.com/2021/06/28/health/coronavirus-vaccines-immunity.html
__________________________________________________

Eric Topol @EricTopol | 8:42 AM · Jun 28, 2021:
Just published nature. A bonus factor after covid vaccination:
germinal center factories for durable, antigen-specific, B cells and plasmoblasts
induced by mRNA vaccination, as determined by lymph node aspirates from vaccinees

https://nature.com/articles/s41586-021-03738-2 * @TheBcellArtist @WUSTLmed
Image-Fig 1. Plasmablast & antibody response to SaRS CoV-2 immunization ( 8:42 AM · Jun 28, 2021 )
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* Jackson S. Turner et al. 2021. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature
Nature (28 June 2021) https://nature.com/articles/s41586-021-03738-2

This is an unedited manuscript that has been accepted for publication.

Abstract

...The persistence of S(spike)-binding GC (germinal centre) B cells and PBs (plasmoblasts, white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens) in draining LNs (lymph nodes) is a positive indicator for induction of long-lived plasma cell responses...Overall, our data demonstrate a remarkable capacity of SARS-CoV-2 mRNA-based vaccines to induce robust and prolonged GC reactions. The induced GC reaction recruited cross-reactive memory B cells as well as newly engaged clones that target unique epitopes (the part of an antigen that is recognized by the immune system) within SARS-CoV-2 S protein. Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response (macromolecules found in extracellular fluids such as secreted antibodies) to vaccination. By inducing robust GC reactions, SARS-CoV-2 mRNA-based vaccines are on track for achieving this outcome.

Eric Topol @EricTopol | 11:45 AM · Jun 28, 2021
Wearable disposable sensors that can also be placed on face masks
to accurately determine covid via a person's breath or environmental exposure
Just out @NatureBiotech

https://nature.com/articles/s41587-021-00950-3 * @wyssinstitute @lrsoenksen @MIT_IMES
Image- 1st p abstract, highlighted ( https://twitter.com/EricTopol/status/1409538541126766599/photo/1 )
Image- infographic, sensors ( https://twitter.com/EricTopol/status/1409538541126766599/photo/2 )
Image- infographic #2, sensors ( https://twitter.com/EricTopol/status/1409538541126766599/photo/3 )
Image- Mask with sensor ( https://twitter.com/EricTopol/status/1409538541126766599/photo/4 )
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* Peter Q. Nguyen et al. 2021. Wearable materials with embedded synthetic biology sensors for biomolecule detection. Nature Biotechnology (28 June 2021). https://nature.com/articles/s41587-021-00950-3

Abstract

Integrating synthetic biology into wearables could expand opportunities for noninvasive monitoring of physiological status, disease states and exposure to pathogens or toxins. However, the operation of synthetic circuits generally requires the presence of living, engineered bacteria, which has limited their application in wearables. Here we report lightweight, flexible substrates and textiles functionalized with freeze-dried, cell-free synthetic circuits, including CRISPR-based tools, that detect metabolites, chemicals and pathogen nucleic acid signatures. The wearable devices are activated upon rehydration from aqueous exposure events and report the presence of specific molecular targets by colorimetric changes or via an optical fiber network that detects fluorescent and luminescent outputs. The detection limits for nucleic acids rival current laboratory methods such as quantitative PCR. We demonstrate the development of a face mask with a lyophilized CRISPR sensor for wearable, noninvasive detection of SARS-CoV-2 at room temperature within 90 min, requiring no user intervention other than the press of a button.

>69 margd: and >72 margd: school filtration

NY State Now Requires Air Filters for Coronavirus in Shopping Malls
Michael Tobias | June 14, 2021

...Governor Andrew Cuomo announced that NY malls will be required to use filters with a high MERV rating or a HEPA rating. Otherwise, they will not be allowed to open. Businesses in general have been instructed to consider air filter upgrades, especially office buildings...

https://www.ny-engineers.com/blog/ny-state-now-requires-air-filters-for-coronavi...

Abu Dhabi to ban unvaccinated people from many public spaces
Tre'Vaughn Howard | June 28, 2021

On Monday, the Abu Dhabi Emergency Crisis and Disasters Committee approved a restriction that would prevent people who have not received a COVID-19 vaccine to enter many public spaces.

...The ban goes into effect August 20, at which point, unvaccinated residents will not be allowed in shopping centers, restaurants, cafes, gyms, museums, theme parks, resorts and sporting activities. The only public place unvaccinated people may shop are retail locations that sell "essential goods such as supermarkets and pharmacies." The ban also applies to universities, public and private schools and nurseries.

The restrictions will not apply to unvaccinated people with approved exemptions or those who are under the age of 16.

On Monday, the U.S. Department of State issued a level 4 travel advisory for the United Arab Emirates, the highest level indicating U.S. residents should not travel to the area due to COVID-19. According to data collected by John Hopkins University, the United Arab Emirates has fully vaccinated nearly 40% of its population.

https://www.cbsnews.com/news/abu-dhabi-bans-unvaccinated-from-public-places/

COVID-19: 'Mix and match' jabs study finds combination of Oxford and Pfizer vaccines creates robust immune response
A study found people who received the AstraZeneca jab followed by a Pfizer dose produced nine times more antibodies.
Thomas Moore | June 29, 2021

...Professor Matthew Snape from the Oxford Vaccine Group said the "mix and match" approach may result in additional protection against coronavirus...a clinical trial comparing the current UK strategy of giving two doses of either the AstraZeneca or Pfizer/BioNTech vaccines against a combination of the two jabs.

Results showed people who received the AstraZeneca vaccine first, followed four weeks later by a Pfizer dose, produced antibody levels nine times higher than those given two doses of the Oxford jab.

Volunteers who were given Pfizer first and AstraZeneca second had antibody levels five times higher than those who received two doses of the Oxford vaccine.

Two doses of the Pfizer jab produced the highest antibody levels, but the T-cell response was higher in people receiving the combination of vaccines...

https://news.sky.com/story/covid-19-mix-and-match-jabs-study-finds-combination-o...
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https://comcovstudy.org.uk/home

Review: "Ivermectin is not a viable option to treat COVID-19 patients."
..."Additional ongoing randomized controlled trials should be completed in order to update our analyses. In the meanwhile, IVM is not a viable option to treat COVID-19 patients, and only should be used within clinical trials context."

Yuani M Roman et al. 2021. Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clinical Infectious Diseases (28 June 2021), ciab591, https://doi.org/10.1093/cid/ciab591 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab591/6310839#.YN...

Accepted manuscript

Abstract
...Conclusions
In comparison to SOC (standard of care) or placebo, IVM (ivermectin) did not reduce all-cause mortality, length of stay or viral clearance in RCTs (randomized controlled trials) in COVID-19 patients with mostly mild disease. IVM did not have an effect on AEs (adverse events) or severe AEs. IVM is not a viable option to treat COVID-19 patients....

Covid: Masks upgrade cuts infection risk, research finds
David Shukman | 6/28/2021

...For most of last year, (Cambridge University NHS Hospitals) followed national guidance which specifies that healthcare workers should wear surgical masks, except in a few limited situations.

Though fluid resistant, these masks are relatively flimsy and loose-fitting and are not meant to screen out infectious aerosols - tiny virus particles that can linger in the air and are now widely accepted as a source of coronavirus infection.

The study found that staff caring for Covid patients on "red" wards faced a risk that was up to 47 times higher than those on "green" or non-Covid wards.

...as the second wave of the pandemic started to hit last December, managers in Cambridge made a local decision to upgrade the protection on red wards.

(3M N99) FFP3 masks have a close fit and are specifically designed to filter out aerosols.

In the weeks following this move, the rate of infections among healthcare workers on red wards dropped spectacularly, quickly falling to the level experienced by staff on green wards where there were no Covid patients...

https://www.bbc.com/news/health-57636360
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Mark Ferris, Rebecca Ferris, Chris Workman, et al. FFP3 respirators protect healthcare workers against infection with SARS-CoV-2. Authorea. June 24, 2021. DOI: 10.22541/au.162454911.17263721/v1 https://www.authorea.com/users/421653/articles/527590-ffp3-respirators-protect-h...

This is a preprint and has not been peer reviewed. Data may be preliminary.

Eric Topol @EricTopol | 10:04 AM · Jun 29, 2021:
The tragedy in Namibia
Now the highest cases per capita in the world and one of the top 3 in fatalities
more than 40% test positivity

@OurWorldInData
Image-graph, cases, Namibia, March-June 2021 ( https://twitter.com/EricTopol/status/1409875436432207882/photo/1 )
Image-graph, deaths, Namibia, March-June 2021 ( https://twitter.com/EricTopol/status/1409875436432207882/photo/2 )

Also, having fended off earlier waves, Australians have less immunity from natural infection?

Covid: How Delta exposed Australia's pandemic weaknesses
Frances Mao | June 29, 2021

...Epidemiologists say the Delta variant has proven to be the most infectious and transmissible of all the strains so far.

Where there were cracks in Australia's defence system, it succeeded in exploiting them.

...Officials documented cases where travellers were catching the virus in quarantine, despite staying in separate rooms.

...Australia has been notoriously strict on gatekeeping who's allowed into the country - with weekly limits on the number of returning citizens and outright bans from some virus hotspots.

When they step off their plane, returnees are greeted by an intimidating coterie of soldiers, police officers and nurses - masked-up and gloved to escort arrivals straight to quarantine.

But the same rigour isn't applied to other workers - like drivers transporting arrivals.

...officials are reporting near 100% household transmission compared to 25% for earlier strains. People there have caught the virus just from passing one another in a shop.

...Just under 5% of the adult population is fully vaccinated, with 29% having received a first dose...

https://www.bbc.com/news/world-australia-57647413

KFF (Kaiser Family Foundation) KFF | 11:04 AM · Jun 28, 2021
#COVIDVaccination projections show variation in (US) states on track to reach 70% of people ages 12+ w/1+ dose by July 4.

40 of 44 states for Asian people
18 of 47 states for White people
13 of 44 states for Hispanic people
5 of 47 states for Black people

https://kff.org/racial-equity-and-health-policy/issue-brief/disparities-in-reach...

Maps (0:16)
https://twitter.com/KFF/status/1409528027558580228

People in longterm care do better it seems than suggested by this paper(?): "...the elderly are a high risk population that warrant specific measures to boost vaccine responses, particularly where variants of concern are circulating."

Eric Topol @EricTopol | 11:32 AM · Jun 30, 2021:
Just out Nature

The deficient immune response to mRNA vaccination for people age 80 and older
Less neutralization antibody, marked after 1st dose, especially an issue w/ key variants,
lower T cell response as well...

https://nature.com/articles/s41586-021-03739-1 *
Image ( https://twitter.com/EricTopol/status/1410259887204880386/photo/1 )

---------------------------------------------------

* Dami A. Collier et al. 2021. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature (30 June 2021) https://www.nature.com/articles/s41586-021-03739-1

This is an unedited manuscript that has been accepted for publication.

Abstract
Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, data are scarce on vaccine efficacy against variants of concern (VOC) in individuals above 80 years of age... Here we analysed immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants and younger health care workers. Serum neutralisation and binding IgG/IgA after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Sera from participants above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type and were more likely to lack any neutralisation against VOC following the first dose. However, following the second dose, neutralisation against VOC was detectable regardless of age. Frequency of SARS-CoV-2 Spike specific B-memory cells was higher in elderly responders versus non-responders after first dose. Elderly participants demonstrated clear reduction in somatic hypermutation of class switched cells. SARS-CoV-2 Spike specific T- cell IFNγ and IL-2 responses decreased with increasing age, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high risk population that warrant specific measures to boost vaccine responses, particularly where variants of concern are circulating.

"the second vaccine dose (Pfizer) induces antibodies for efficient neutralization of the D614G and the B.1.1.7, while the titers for the B.1.351 variant were lower"

COVID mRNA vaccines induce antibodies against three SARS-CoV-2 variants
Angela Betsaida B. Laguipo | Jul 1 2021

...BNT162b2 vaccine-induced antibody responses

To arrive at the study findings, the researchers characterized the BNT162b2 vaccine-induced antibody responses in the sera of 180 Finnish healthcare workers who received two doses of COVID-19 vaccine with three weeks intervals.

From there, they checked for SARS-CoV-2 S1-specific IgG, Immunoglobulin A (IgA), and the immunoglobulin M (IgM) antibody responses and neutralization titers for three SARS-CoV-2 variants, namely the D614G, B.1.1.7, and the B.1.351 variants.

The team revealed that receiving a two-dose vaccination yields high levels of anti-S1 IgG antibodies in 100 percent of the vaccinees. Further, the team noted that the second vaccine dose induces antibodies for efficient neutralization of the D614G and the B.1.1.7, while the titers for the B.1.351 variant were lower...

https://www.news-medical.net/news/20210701/COVID-mRNA-vaccines-induce-antibodies...

-------------------------------------------------------

Jalkanan, P., Kolehmainen, P., Julkunen, et al. (2021). COVID-19 mRNA vaccine-induced antibody responses against three SARS-CoV-2 variants. Nature Communications 12, Article number: 3991 (28 June 2021) . https://www.nature.com/articles/s41467-021-24285-4

Abstract
As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of more than 20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.

"Adjusted (mRNA) vaccine effectiveness was 91% ... with full vaccination and 81%...with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower... in partially or fully vaccinated participants than in unvaccinated participants... and the duration of illness was shorter, with 2.3 fewer days spent sick in bed."

Mark G. Thompson et al. 2021. Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines. NEJM June 30, 2021. DOI: 10.1056/NEJMoa2107058 https://www.nejm.org/doi/10.1056/NEJMoa2107058

Abstract
Background
...in real-world conditions.

Methods
3975 health care personnel, first responders, and other essential and frontline workers

Results
SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (at least 14 days after dose 2), 11 partially vaccinated (at least 14 days after dose 1 and fewer than 14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (fewer than 14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% ... with full vaccination and 81%...with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower... in partially or fully vaccinated participants than in unvaccinated participants... and the duration of illness was shorter, with 2.3 fewer days spent sick in bed...

Conclusions
Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination.

Eric Topol (Scripps MD scientist) @EricTopol | 11:37 PM · Jun 30, 2021:
Thailand, for more than 12 months of the pandemic had total containment,
but now with 10% 1st-dose vaccinated and ~30% Delta variant (http://outbreak.info)
things have drastically changed

@OurWorldInData
Image-graph cases ( https://twitter.com/.../status/1410442448707284994/photo/1 )
Image-graph deaths ( https://twitter.com/.../status/1410442448707284994/photo/2 )

😥

---------------------------------------------------

Mike Honey Syringe @Mike_Honey_ | 2:09 AM · Jul 1, 2021:
Replying to @EricTopol and @OurWorldInData
Here's the latest variant picture for Thailand. The recent Delta samples have all been in Bangkok or adjacent provinces.
Data from GISAID via http://nextstrain.org (community dataset) for this dataviz project:
https://github.com/Mike-Honey/covid-19-genomes#readme
Image-lineage in Bangkok and adjacent provinces ( https://twitter.com/.../status/1410480537437761537/photo/1 )

Eric Topol @EricTopol | 10:22 PM · Jun 30, 2021:
The 5 US states leading case growth (per capita), achieving at or near dominance of the Delta variant, and their vaccination rates. US fully vaccinated avg is 47%.
The 10+ cases/100,000 people are still relatively low, but the trend is notable

Image-table 5 states' % Delta, % vaxxed ( https://twitter.com/EricTopol/status/1410423621558804482/photo/1 )

Image-graph 5 states' # cases June 2021 ( https://twitter.com/EricTopol/status/1410423621558804482/photo/2 )

Public Awareness of Long COVID & Motivation to Get Vaccinated (Quantitative Research)
June 2021
20 p
https://preventepidemics.org/wp-content/uploads/2021/06/Report_Long_COVID_Survey...

Executive Summary
1. Nearly 40% of Americans report that they are not vaccinated. Unvaccinated Americans tend to:
•be ages 18-29
•be female
•have a household income under $50K
•have an education less than college
•be Republican or Independent
•live in the Midwest or South and/or a rural community
•be African American

2. Of those who are unvaccinated, 84% are vaccine hesitant, including 41% who say they will definitely not get the vaccine –mainly driven by Republicans and Independents, as well as those who live in the Midwest, South and rural areas.

3. More than 30% of Americans are unaware of long COVID, including 39% of the vaccine hesitant group.Among those who are aware, 39% are not concerned about it. After reading a description of the condition, 39% of all Americans remain unconcerned.

4. Half of vaccine-hesitant Americans believe the message that “Getting the COVID-19 vaccine is the best way to prevent COVID-19 and its potential long-term complications”. The other half who do not believe this message primarily indicate that there is still too much unknown about the vaccine.

5. Video testimonials from people suffering from long COVID significantly raise concern and prompt greater willingness to consider vaccination. 64% of Americans become more concerned and 39% of those unvaccinated, including 31% who are vaccine hesitant, are motivated to consider getting the vaccine. The testimonials are most effective among 18-to 29-year-olds, Hispanics and urbanites.

Joint COVAX Statement on the Equal Recognition of Vaccines
WHO | 1 July 2021

...COVAX urges all regional, national & local government authorities to recognise as fully vaccinated all people who have received #COVID19 vaccines that have been deemed safe & effective by the World Health Organization...

https://www.who.int/news/item/01-07-2021-joint-covax-statement-on-the-equal-reco...

Opinion
It’s Time for the F.D.A. to Fully Approve the mRNA Vaccines
Eric J. Topol | July 1, 2021

...Some people who understand that the “E” in “E.U.A.” stands for “emergency” are waiting for full F.D.A. approval before they receive a shot. Others may not get immunized unless their employers require it, and many organizations — including, reportedly, the military — are waiting for the vaccines to be fully approved before instituting such mandates.

...The E.U.A.s were granted more than six months ago. That’s more than ample time for the F.D.A. to conduct plant inspections and review the applications.

...Delta...

https://www.nytimes.com/2021/07/01/opinion/fda-vaccines-full-approval.html

ETA:
Jesse O’Shea MD, MSc @JesseOSheaMD
Phase 1/2a COVID-19 vaccine study (n=20) showed durable humoral and cellular immune responses generated through at least eight months.
The average neutralizing titer at eight months exceeded that average at 29 days!

Reassuring results against variants and durability of J&J vaccine. Still waiting on large vaccine efficacy trials, Sisonke and ENSEMBLE 2. So far, the data is not quite there yet for guidelines to recommend boosting by an mRNA dose. This may come down to these two VE trials…
------------------------------------------------
Positive New Data for Johnson & Johnson Single-Shot COVID-19 Vaccine on Activity Against Delta Variant and Long-lasting Durability of Response
J&J | July 2021

Demonstrated strong neutralizing antibody activity against the Delta (B.1.617.2) variant
Persistent immune responses through at least eight months

https://www.jnj.com/positive-new-data-for-johnson-johnson-single-shot-covid-19-v...
_______________________________________

Johnson & Johnson vaccine seems to stand up against delta variant, preliminary research suggests
Vaccines may offer longer protection than some scientists initially anticipated.
Sony Salzman | July 1, 2021

...In a laboratory experiment, researchers analyzed the blood of 10 people who had been vaccinated with the single-shot Johnson & Johnson vaccine, and tested it against multiple concerning variants, including delta.

They found that the vaccine appeared to work against new variants, as indicated by so-called "neutralizing antibody titers" and other indications of immune system response.

...Prior data has indicated that other vaccines, including those made by Pfizer and Moderna, are likely to hold up against the delta variant. But some experts worried the Johnson & Johnson vaccine, which unlike the others, only includes one dose, might not fare as well.

...Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center...said another reassuring finding of the study was that people vaccinated with the Johnson & Johnson shot appeared to have a strong immune system response up to eight months later...

https://abcnews.go.com/Health/jj-vaccine-stand-delta-variant-preliminary-researc...

Opinion: Health-care providers must mandate that their workers be vaccinated. The Hippocratic oath demands it.
Ashish K. Jha (dean of the Brown University School of Public Health) | July 1, 2021

...In 2021, the responsibility of every hospital to the health and safety of its patients means protecting vulnerable patients from covid-19. Patients shouldn’t have to worry that being in the hospital puts them at risk for serious disease. The best way to do that is to ensure that everyone who comes into contact with patients is vaccinated.

https://www.washingtonpost.com/opinions/2021/07/01/health-care-workers-must-be-v...

>94 margd: J&J's effectiveness against delta variant, contd. "only a 1.6-fold reduction"

Jesse O’Shea MD, MSc @JesseOSheaMD | 8:57 AM · Jul 2, 2021:
J&J single dose vaccine only reduced neutralization titers 1.6 fold by Delta variant…
-----------------------------------------------
Mandy Jongeneelen et al. 2021. Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern. BioRxiv (July 1, 2021)
doi: https://doi.org/10.1101/2021.07.01.450707

This article is a preprint and has not been certified by peer review

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and recently emerging variants with substitutions in the Spike protein have led to growing concerns over increased transmissibility and decreased vaccine coverage due to immune evasion. Here, sera from recipients of a single dose of our Ad26.COV2.S COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants of concern. All tested variants demonstrated susceptibility to Ad26.COV2.S-induced serum neutralization albeit mainly reduced as compared to the B.1 strain. Most pronounced reduction was observed for the B.1.351 (Beta (S Africa); 3.6-fold) and P.1 (Gamma (Brazil); 3.4-fold) variants that contain similar mutations in the receptor-binding domain (RBD) while only a 1.6-fold reduction was observed for the widely spreading B.1.617.2 (Delta (India)) variant.

Longer gap between COVID-19 vaccine doses may increase immune response
James Kingsland | July 2, 2021

A new study provides reassurance that a longer gap between the first and second doses of the Oxford-AstraZeneca vaccine will not compromise a person’s immune response.

A gap of up to 45 weeks actually led to a stronger immune response compared with the recommended interval.

A “booster” jab more than 6 months after the second dose further strengthened immunity, including against existing variants.

There were lower incidences of mild vaccine side effects after the second and third doses than after the first dose...

https://www.medicalnewstoday.com/articles/longer-gap-between-covid-19-vaccine-do...

------------------------------------------------------------------------

Amy Flaxman et al. 2021. Tolerability and Immunogenicity After a Late Second Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222). Lancet (preprint) 35 Pages Posted: 28 Jun 2021. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3873839

Abstract
...Interpretation: A longer delay before the second dose of ChAdOx1 nCoV-19 leads to an increased antibody titre after the second dose. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.

Dr. Alex Huffman (Chem, U Denver) @HuffmanLabDU | 12:29 PM · Jul 2, 2021:
https://twitter.com/HuffmanLabDU/status/1410998996856758277

Great new study on #HEPA air cleaners by Lindsley et al. out today via @CDCMMWR:
masks reduced aerosol by 72%, HEPA by 65%, together by 90%.*
Conclusions are consistent with messages for months, but important that #CDC amplifying this strategy.

2/ "The use of masks without air cleaners reduced the aerosol exposure of the receivers by 72%, and the use of air cleaners without masks reduced the exposure by up to 65%. When used together, the HEPA air cleaners and masks reduced exposure to respiratory aerosols by up to 90%."
Image-bar graph, masks/none, location of HEPA filters ( https://twitter.com/HuffmanLabDU/status/1410998989265137667/photo/1 )

3/ "These findings suggest that the use of portable HEPA air cleaners and universal masking can each reduce exposure to simulated SARS-CoV-2 aerosols in indoor environments, with larger reductions occurring when air cleaners and masking are used together." *

4/ The study used simulated SARS-CoV-2 aerosol emitted from a manikin in a fixed location, w/ two portable HEPA cleaners at varied locations in room. Also tested w/ & w/out mask use. Always caveats & limitations, but study highlights importance of both masks & room filtration.
Image-room setup ( https://twitter.com/HuffmanLabDU/status/1410998993962737664/photo/1 )
Image-table aerosol measurements ( https://twitter.com/HuffmanLabDU/status/1410998993962737664/photo/2 )

5/ The #MMWR report references several other studies to show similar efficacy of HEPA filters, e.g. the Curtius et al. study showing 90% reduction of aerosol w/in 5 min. in a classroom in Germany....

6/ And the study by Burgmann & Janoske "Transmission and reduction of aerosols in classrooms using air purifier systems"...

7/ The study could have also cited, among others, the nice, recent study by @KirstyBuising
@RobynSchofield3 et al. showing reduction of aerosol in a hospital.
"Use of portable air cleaners to reduce aerosol transmission on a hospital COVID-19 ward"...

8/ Addition of air cleaners like portable HEPA filters are an important part of keeping indoor air clean from infectious respiratory aerosols and all manner of suspended particles (like wildfire smoke, cooking aerosol, urban pollution PM)...

9/ HEPA filters have been championed by indoor air experts as a key part of the strategy to offer in-person learning in the Fall and beyond. See this thread on an excellent example by NYC schools, with further comment & resources on filtration in schools...

----------------------------------------------------------
* Lindsley WG, Derk RC, Coyle JP, et al. Efficacy of Portable Air Cleaners and Masking for Reducing Indoor Exposure to Simulated Exhaled SARS-CoV-2 Aerosols — United States, 2021. MMWR Morb Mortal Wkly Rep. ePub: 2 July 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7027e1external icon.
https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e1.htm

Summary
What is already known about this topic?
Ventilation systems can be supplemented with portable high efficiency particulate air (HEPA) cleaners to reduce the number of airborne infectious particles.

What is added by this report?
A simulated infected meeting participant who was exhaling aerosols was placed in a room with two simulated uninfected participants and a simulated uninfected speaker. Using two HEPA air cleaners close to the aerosol source reduced the aerosol exposure of the uninfected participants and speaker by up to 65%. A combination of HEPA air cleaners and universal masking reduced exposure by up to 90%.

What are the implications for public health practice?
Portable HEPA air cleaners can reduce exposure to simulated SARS-CoV-2 aerosols in indoor environments, especially when combined with universal masking.

The Last—And Only—Foreign Scientist in the Wuhan Lab Speaks Out
Virologist Danielle Anderson paints a very different picture of the Wuhan Institute.
Michelle Fay Cortez | June 27, 2021

...From her first visit before it formally opened in 2018, (Danielle) Anderson was impressed with the institute’s maximum biocontainment lab. The concrete, bunker-style building has the highest biosafety designation, and requires air, water and waste to be filtered and sterilized before it leaves the facility. There were strict protocols and requirements aimed at containing the pathogens being studied, Anderson said, and researchers underwent 45 hours of training to be certified to work independently in the lab.

...Entering and exiting the facility was a carefully choreographed endeavor, she said. Departures were made especially intricate by a requirement to take both a chemical shower and a personal shower—the timings of which were precisely planned.

...The Wuhan lab uses a bespoke method to make and monitor its disinfectants daily, a system Anderson was inspired to introduce in her own lab. She was connected via a headset to colleagues in the lab’s command center to enable constant communication and safety vigilance—steps designed to ensure nothing went awry.

...Anderson said no one she knew at the Wuhan institute was ill toward the end of 2019. Moreover, there is a procedure for reporting symptoms that correspond with the pathogens handled in high-risk containment labs...

‘I’m Not Naive’

It’s not that it’s impossible the virus spilled from there. Anderson, better than most people, understands how a pathogen can escape from a laboratory. SARS, an earlier coronavirus that emerged in Asia in 2002 and killed more than 700 people, subsequently made its way out of secure facilities a handful of times, she said.

If presented with evidence that such an accident spawned Covid-19, Anderson “could foresee how things could maybe happen,” she said. “I’m not naive enough to say I absolutely write this off.”

And yet, she still believes (SARS-CoV-2) most likely came from a natural source. Since it took researchers almost a decade to pin down where in nature the SARS pathogen emerged, Anderson says she’s not surprised they haven’t found the “smoking gun” bat responsible for the latest outbreak yet.

The Wuhan Institute of Virology is large enough that Anderson said she didn’t know what everyone was working on at the end of 2019. She is aware of published research from the lab that involved testing viral components for their propensity to infect human cells. Anderson is convinced no virus was made intentionally to infect people and deliberately released—one of the more disturbing theories to have emerged about the pandemic’s origins.

Gain of Function

Anderson did concede that it would be theoretically possible for a scientist in the lab to be working on a gain of function technique to unknowingly infect themselves and to then unintentionally infect others in the community. But there’s no evidence that occurred and Anderson rated its likelihood as exceedingly slim....

...Anderson does think an investigation is needed to nail down the virus’s origin once and for all. She’s dumbfounded by the portrayal of the lab by some media outside China, and the toxic attacks on scientists that have ensued.

...The elements known to trigger infectious outbreaks—the mixing of humans and animals, especially wildlife—were present in Wuhan, creating an environment conducive for the spillover of a new zoonotic disease. In that respect, the emergence of Covid-19 follows a familiar pattern. What’s shocking to Anderson is the way it unfurled into a global contagion...

https://www.bloomberg.com/news/features/2021-06-27/did-covid-come-from-a-lab-sci...

:D Good news for India and the rest of us: Covaxin requires regular refrigeration, and India is prepared to mfr in great quantities. https://www.bmj.com/content/373/bmj.n997

Phase 3: Covaxin (codenamed as BBV152) is an inactivated virus -based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research. (Wikipedia)

Dr Sumaiya Shaikh @Neurophysik | 6:11 PM · Jul 2, 2021:
https://twitter.com/Neurophysik/status/1411085134938447878

Covaxin phase 3 is out as a preprint:
A quick read:

1. Double-blind
2. Randomised
3. Multicentre
4. Placebo-controlled
5. Adults 18-98 yo
6. 1:1 ratio of total 24419 people (n = 12221) or placebo (n = 12198)
7. Two doses of BBV152 Covaxin intramuscular
8. Recruitment between 16 Nov 2020 & 7 Jan 2021
9. Primary outcome: Symptomatic COVID-19 cases 2 weeks after the 2nd dose.
10. Secondary outcomes: Efficacy in age (18 -60 years & 60+ yo) & in people with co-morbidities
11. Safety, reactogenicity, & consistency of immune responses recorded from 3 consecutive lots.
12: Efficacy: Overall 77.8% (95% CI: 65.2,86.4)
*lower from the 81% reported earlier, but not bad*

After 2 doses,
A. Symptomatic cases= 93.4%
(24 in vaccine & 106 cases in placebo)
B. Asymptomatic cases = 63.6%
C: Severe cases: 93.4%
D: Against the Delta variant: 65.2%
E: Total efficacy in 60+ yo: 67·8% for 1858 total in the group
F: Total efficacy in young under 60 yo: 79·4% for 15,115 total in the group

13: Side Effects
A: No "statistically significant" differences in serious adverse events between vaccine & placebo
Total serious events in 99- 39 in vaccine & 60 in placebo.
B: No cases of anaphylaxis or vaccine-related deaths
C: 2 serious adverse events reported
D: Most reported side effects:
headache, pyrexia, fatigue and myalgia in less than 1% in both groups.
E: Rates of local and systemic side effects reported (vaccine vs placebo):
mild 11·2% vs 10·8%
moderate 0·8% vs 1·1%
severe 0·3% vs 0·4%
F: Unsolicited side effects were reported by 1·8% and 1·7% of vaccines and placebo respectively.
G: Side effects were lower after the second dose than the first, higher in vaccine group
H: Overall, 12·4% reported side effects in over 25K people

14. Deaths:
A: Total 15 out of 24419 - none reported due to vaccine
B: 6 due to COVID-19
C: 5 in vaccinated people
Causes: Cerebellar haemorrhage, haemorrhagic stroke, ovarian cancer, sudden cardiac death & COVID-19.
D: 10 in placebo: 5 from COVID
E: 2 with unknown causes

15.
A: 7058 (27·5%) had at least one comorbidity
B: 30% were already seropositive at baseline and hence excluded in analysis, but were included in the safety profiling.

16. Follow-ups:
A good number of people dropped off, withdrew consent, etc. the study along the way.
Need more info on why and how that happened.
Image-dropouts flowchart ( https://twitter.com/Neurophysik/status/1411085154584571913/photo/1 )
--------------------------------------------------------------
Raches Ella et al. 2021. Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial. MedRxiv (July 2, 2021)
doi: https://doi.org/10.1101/2021.06.30.21259439 https://www.medrxiv.org/content/10.1101/2021.06.30.21259439v1

This article is a preprint and has not been certified by peer review.

:D

Eric Topol @EricTopol | 1:22 PM · Jul 3, 2021
Over time, in people with prior covid,
there is increased neutralization antibody potency to variants of concern (Alpha, Beta, Gamma).
New @ImmunityCP (and good to see)
Image (https://twitter.com/EricTopol/status/1411374762975137793/photo/1)
------------------------------------------------

Saya Moriyama et al. 2021. Temporal Maturation of Neutralizing Antibodies in COVID-19 Convalescent Individuals Improves Potency and Breadth to Circulating SARS-CoV-2 Variants. Immunity Open Access. Published:July 02, 2021. DOI:https://doi.org/10.1016/j.immuni.2021.06.015 https://cell.com/immunity/fulltext/S1074-7613(21)00259-4

Highlights
1 Qualitative changes in plasma neutralizing antibody are longitudinally analyzed.
2 Affinity-matured antibodies to viral conserved site are durably elicited.
3 Neutralizing potency and breadth to SARS-CoV-2 variants increase with time.
4 Serological immunity evolves with time to counter SARS-CoV-2 variants.

Abstract
Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity and protection against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers, but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and B.1.1.28.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.

Joseph Allen (Harvard SPH) @j_g_allen | 9:41 AM · Jul 3, 2021:
https://twitter.com/j_g_allen/status/1411319302322638851
https://threadreaderapp.com/thread/1411319302322638851.html (25 tweets)

I study the impact of CO2 on human health so I figured I would weigh in on this JAMA article purporting to show masks create high and unsafe CO2 exposures for kids. (spoiler alert: they don't)

(I'm not linking to the study because I'm certain it will be retracted)

THREAD...

...Among unvaccinated Americans, 60 percent believe U.S. officials are exaggerating the delta variant’s risk, compared with 18 percent who say they are describing it accurately; 64 percent of vaccinated Americans say officials are accurately describing the strain.

Again, there is a sharp partisan divide, with 57 percent of Republicans saying officials are exaggerating the delta variant’s risk, compared with 39 percent of independents and 12 percent of Democrats. There is also an educational divide, with 59 percent of those with college degrees calling the warnings accurate, compared with 38 percent of those who do not have degrees.

https://www.washingtonpost.com/politics/post-abc-poll-biden/2021/07/03/54e95b6e-...

What drives or detracts from vaccine trust?

Eric Topol @EricTopol | 11:08 AM · Jul 4, 2021:

A large survey of 13,000 Americans and Danes
"The strongest predictors of vaccine skepticism ... were individual differences in political cynicism..
and in conspiratorial thinking"

Image -factors assoc w vaccine support ( https://twitter.com/EricTopol/status/1411703393035321345/photo/1 )
Image - 1st p highlighted ( https://twitter.com/EricTopol/status/1411703393035321345/photo/2 )
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Michael Bang Petersen et al. 2021. Transparent communication about negative features of COVID-19 vaccines decreases acceptance but increases trust. PNAS July 20, 2021 118 (29) e2024597118; https://doi.org/10.1073/pnas.2024597118 https://www.pnas.org/content/118/29/e2024597118

Abstract

During the rapid development and rolling out of vaccines against COVID-19, researchers have called for an approach of “radical transparency,” in which vaccine information is transparently disclosed to the public, even if negative information can decrease vaccine uptake. Consistent with theories about the psychology of conspiracy beliefs, these calls predict that a lack of transparency may reduce trust in health authorities and may facilitate the spread of conspiracy theories, which may limit the long-term capabilities of health authorities during and after the pandemic. On the basis of preregistered experiments conducted on large, representative samples of Americans and Danes (N more than 13,000), the current study contrasts the effects of vague vaccine communication with transparent communication, which discloses either positive or negative vaccine features. The evidence demonstrates that transparent negative communication may indeed harm vaccine acceptance here and now but that it increases trust in health authorities. Furthermore, the alternative of vague, reassuring communication does not increase vaccine acceptance either and leads to both lower trust and higher endorsement of conspiracy theories.

:)

EXCLUSIVE S.Korea in talks with mRNA vaccine makers to make up to 1 bln doses -govt official
Sangmi Cha | July 5, 2021

South Korea is in talks with mRNA vaccine makers including Pfizer (PFE.N) and Moderna (MRNA.O) to produce COVID-19 shots in the country and is ready to offer the capacity to make up to 1 billion doses immediately, a senior government official said.

The plan, if agreed, would help ease tight global supply of COVID-19 vaccines, particularly in Asia which lags North America and Europe in vaccine rollouts, and put South Korea a step closer to its ambition to become a major vaccine manufacturing centre.

South Korea already has deals to locally produce three coronavirus vaccines developed by AstraZeneca (AZN.L)/Oxford University, Novavax (NVAX.O), and Russia. It also has a vaccine bottling and packaging deal with Moderna...

https://www.reuters.com/business/healthcare-pharmaceuticals/exclusive-skorea-tal...

Japan seeks to have vaccine passports accepted by over 10 nations
Jul 5, 2021

Japan is making arrangements for its COVID-19 vaccination passports to be accepted by over 10 nations, including Italy, France and Greece, after the certificate program begins in late July

If the agreements are reached, certificate holders will be exempt from quarantine or showing negative test results for COVID-19 when traveling from Japan to those countries.

But the Japanese government plans to continue requiring travelers entering Japan, including returnees, to quarantine for two weeks even if they have been vaccinated. The position has complicated negotiations with countries such as Singapore and Israel, which have called for mutual exemption, the sources said.

...Japan has a sweeping ban on new entries of foreign nationals to cope with the pandemic, except those with approval given under “special exceptional circumstances.” Travelers entering Japan are asked to stay at home or a designated facility for 14 days after arrival.

The European Union has its own digital vaccination passport for EU citizens and residents. Certificate holders are exempt from testing and quarantine when traveling to a different country within the bloc.

The World Health Organization does not endorse making vaccine passports mandatory for travelers as equal access to COVID-19 vaccines has not been ensured.

https://www.japantimes.co.jp/news/2021/07/05/national/japan-covid-19-vaccination...

A preprint, not yet peer-reviewed, but based on huge Ontario database. Good results, but interesting to review Table 3 ( https://twitter.com/BogochIsaac/status/1412060322643464196/photo/1 ) for protection from symptomatic infections and hospitalization/death, with one or two doses of Pfizer/Moderna/ Astrozeneca, against variants first reported in UK (Alpha, B.1.1.7), S Africa (Beta, B.1.351), Brazil (Gamma, P.1), and India (Delta, B.1.617.2).

Sharifa Nasreen et al. 2021. MedRxiv (July 3, 2021) Effectiveness of COVID-19 vaccines against variants of concern , Canada. https://doi.org/10.1101/2021.06.28.21259420 https://www.medrxiv.org/content/10.1101/2021.06.28.21259420v1.full.pdf

preprint

ABSTRACT:
"...population-wide vaccination, laboratory testing, and health administrativedatabasesin Ontario, Canada..."

...Results:Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 than BNT162b2 and ChAdOx1. Full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 and mRNA-1273 against Alpha. Protection against symptomatic infection caused by Beta/Gamma was lower with partial vaccination for ChAdOx1 than mRNA-1273. Against Delta, vaccine effectiveness after partial vaccination tended to be lower than against Alpha for BNT162b2 and mRNA-1273, but was similar to Alpha for ChAdOx1. Full vaccination with BNT162b2 increased protection against Delta to levels comparable to Alpha and Beta/Gamma.Vaccine effectiveness against hospitalization or death caused by all studied VOCs was generally higher than for symptomatic infection after partial vaccination with all three vaccines.

Conclusions: Our findings suggest that even a single dose of these 3 vaccine products provide good to excellent protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern ( Alpha (B.1.1.7, UK), Beta(B.1.351, S Africa), Gamma (P.1, Brazil), and Delta (B.1.617.2, India) variants of concern (VOCs) ), and that 2 doses are likely to provide even higher protection...

Can COVID-19 vaccines affect periods?
Maria Cohut, Ph.D. on July 2, 2021

There have been several reports linking COVID-19 vaccines to changes to people’s menstrual cycles. What do we know about this potential link so far? Medical News Today has spoken with researchers, physicians, and people who have experienced changes to their own cycles after receiving their vaccines to find out.

...Information that The Times obtained indicates that in the United Kingdom, the Medicines & Healthcare Products Regulatory Agency received almost 4,000 reports of changes to people’s periods after a COVID-19 vaccine by May 17, 2021.

Of these, 2,734 cases occurred after the Oxford-AstraZeneca vaccine, 1,158 occurred after the Pfizer-BioNTech vaccine, and 66 occurred after the Moderna vaccine.

Due to these reports, many questions have arisen. How might a person’s menstrual cycle change after a vaccine? Are these really COVID-19-related side effects, or are they due to stress and other life changes that might coincide with getting the vaccine?

To find out more, MNT has spoken with four women with lived experiences of changes to their periods after getting a COVID-19 vaccine...

https://www.medicalnewstoday.com/articles/can-covid-19-vaccines-affect-periods

Eric Feigl-Ding @DrEricDing | 1:02 AM · Jul 5, 2021
Florida cases have risen ~50% in 2 weeks.
Florida is one of the states with least #COVID19 safety measures.
Maybe banning mask rules and banning vaccination verification was a bad idea.

Image-graph confirmed cases June 2021, FL AR, MO, OK, NV, LA
https://twitter.com/DrEricDing/status/1411913368533938178/photo/1

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Jonathan Reiner @JReinerMD | 12:56 PM · Jul 4, 2021
Florida is averaging 2,241 cases/day, a 55% increase over the last 14 days.
That’s 17% of all cases in the US. Florida needs to surge its vaccine effort.

Quote Tweet
Arthur Caplan @ArthurCaplan · Jul 3
6 Rescuers at Condo in Surfside, Fla., Test Positive for Virus - The New York Times https://nytimes.com/2021/07/03/us/surfside-rescue-workers-covid.html

Eric Topol @EricTopol | 5:30 PM · Jul 5, 2021:
A new prospective cohort study of more than 400 people with mild to moderate (outpatient) covid at 7-9 months: nearly 1 of 3 had persistent symptoms #LongCovid

@AnnalsofIM https://acpjournals.org/doi/10.7326/M21-0878 *
by@mayssamnehme and colleagues

Image-table symptoms at 7-9 months, age, gender, ( https://twitter.com/EricTopol/status/1412162077905473537/photo/1 )
-----------------------------------------------------------
*
Mayssam Nehme et al. 2021. Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting. Annals of Internal Medicine ( 6 July 2021 ) https://doi.org/10.7326/M21-0878

*
Mayssam Nehme et al. 2021. Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting. Annals of Internal Medicine ( 6 July 2021 ) https://doi.org/10.7326/M21-0878

Abstract
Background...

Objective:
To characterize symptoms 7 to 9 months after diagnosis of COVID-19.

Design:
Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis.

Setting...

Participants...

Measurements:
A standardized interview of symptoms consistent with COVID-19, with grading of intensity.

Results:
Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%).

Limitation...

Conclusion:
Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients.

The Lambda COVID-19 variant: What do we know about it?
Solarina Ho | July 5, 2021

TORONTO -- A recently designated COVID-19 variant of interest by the World Health Organization is coming under scrutiny as more cases are being detected in multiple countries, and amid concerns that it carries mutations that could potentially make it more resistant to neutralizing antibodies.

The newly labelled Lambda variant, or C.37, was first detected as early as last August 2020 in Peru and was being monitored as an alert for some time prior to its new designation. As of mid-June, the variant had been detected in 29 countries or territories with a particularly high prevalence in South America.

“Lambda has been associated with substantive rates of community transmission in multiple countries, with rising prevalence over time concurrent with increased COVID-19 incidence,” the global health agency wrote in its Weekly Epidemiological Update published on June 15.
Coronavirus Coverage

“Lambda carries a number of mutations with suspected phenotypic implications, such as a potential increased transmissibility or possible increased resistance to neutralizing antibodies.”

The WHO said there was currently limited evidence on what the impact of these mutations will mean and that further studies were necessary to better understand how to contain the spread and how the vaccines will hold up against the variant...

https://www.ctvnews.ca/health/coronavirus/the-lambda-covid-19-variant-what-do-we...

______________________________________________
"...mutations of the lambda variant spike protein caused a partial resistance to vaccine elicited serum and Regeneron monoclonal antibodies...current vaccines will provide protection against variants identified to date..."

Study says mRNA COVID vaccines are effective against Lambda variant
Sally Robertson | Jul 5 2021

...The researchers found that while pseudotyped virus expressing the C.37 viral spike protein was less susceptible to vaccine-elicited neutralizing antibodies, the reduction in neutralization was only minor.

...The team – from the New York University Grossman School of Medicine – says the study findings also suggest that Regeneron’s REGN-COV2 cocktail of monoclonal antibodies should be effective against C.37.

https://www.news-medical.net/news/20210705/Study-says-mRNA-COVID-vaccines-are-ef...

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Takuya Tada et al. 2021. SARS-CoV-2 Lambda Variant Remains Susceptible to Neutralization by mRNA Vaccine-elicited Antibodies and Convalescent Serum. BioRxiv (July 3, 2021) doi: https://doi.org/10.1101/2021.07.02.450959 https://www.biorxiv.org/content/10.1101/2021.07.02.450959v1

This article is a preprint and has not been certified by peer review

Abstract
The SARS-CoV-2 lambda variant (lineage C.37) was designated by the World Health Organization as a variant of interest and is currently increasing in prevalence in South American and other countries. The lambda spike protein contains novel mutations within the receptor binding domain (L452Q and F490S) that may contribute to its increased transmissibility and could result in susceptibility to re-infection or a reduction in protection provided by current vaccines. In this study, the infectivity and susceptibility of viruses with the lambda variant spike protein to neutralization by convalescent sera and vaccine-elicited antibodies was tested. Virus with the lambda spike had higher infectivity and was neutralized by convalescent sera and vaccine-elicited antibodies with a relatively minor 2.3-3.3-fold decrease in titer on average. The virus was neutralized by the Regeneron therapeutic monoclonal antibody cocktail with no loss of titer. The results suggest that vaccines in current use will remain protective against the lambda variant and that monoclonal antibody therapy will remain effective.

...Discussion
Virus with the lambda spike protein, like several VOC variant spike proteins showed a partial resistance to neutralization by vaccine-elicited antibodies and convalescent sera; however the average 3-fold decrease in neutralizing titer against the variant is not likely to cause a significant loss of protection against infection as the average neutralization IC50 titer by the sera of BNT162b2 and mRNA-1273 vaccinated individuals was about 1:600, a titer that is above that in the sera of individuals who recovered from infection with the parental D614G virus. A small fraction of vaccinated individuals had serum antibody titers less than average but whether this will lead to reduced protection from variant infection will need to be determined in epidemiological studies.

The resistance of the lambda variant to antibody neutralization was caused by the L452Q and F490S mutations. The L452R mutation of the California B.1.427/B.1.429 is associated with a 2-fold increase in virus shedding by infected individuals and a 4-6.7-129fold and 2-fold decrease in neutralizing titer by the antibodies of convalescent and vaccinated donors, respectively. The degree of neutralization resistance provided by L452Q was similar to that of L452R. Amino acid residues 490 and 484 lie close together on the top of the RBD and are therefore in a position to affect the binding of neutralizing antibody. The E484K mutation in the B.1.351, B.1.526, P.1 and P.3spike proteins causes partial resistance to neutralization... Similarly, the F490S mutation also caused a 2-3-fold resistance to neutralization, demonstrating the importance of the amino acid as an antibody recognition epitope. While the lambda variant was slightly resistant to REGN10987, it was neutralized well by the cocktail with REGN10933.

This study suggests that the L452Q and F490S mutations of the lambda variant spike protein caused a partial resistance to vaccine elicited serum and Regeneron monoclonal antibodies. While our findings suggest that current vaccines will provide protection against variants identified to date, the results do not preclude the possibility that novel variants will emerge that are more resistant to current vaccines. The findings highlight the importance of wide-spread adoption of vaccination which will protect individuals from disease, decrease virus spread and slow the emergence of novel variants.

variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), originally detected in California...epsilon...carries three spike protein mutations that confer resistance to neutralizing antibodies generated by mRNA vaccines or by #SARSCoV2 infection...

Matthew McCallum et al. 2021. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science 01 Jul 2021:eabi7994 DOI: 10.1126/science.abi7994 https://science.sciencemag.org/content/early/2021/06/30/science.abi7994

Abstract
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based mRNA vaccine or convalescent individuals exhibited neutralizing titers, which were reduced 2-3.5 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The L452R mutation reduced neutralizing activity of 14 out of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 out of 10 NTD-specific mAbs since the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and formation of a new disulphide bond, as revealed by mass spectrometry and structural studies.

...Discussion
...Understanding the newfound mechanism of immune evasion of the emerging variants, such as the signal peptide modification described herein, is as important as sequence surveillance itself to successfully counter the ongoing pandemic.

Delta plus variant of SARS-CoV-2: How does it compare with the delta variant?
Minseo Jeong | July 6, 2021

A novel SARS-CoV-2 variant, the delta plus variant, has been identified in over 10 countries. Health authorities are raising concerns that the variant may have an increased ability to transmit, but they also note that this variant’s transmissibility is likely similar to that of the preexisting delta variant...

...The delta plus variant is a sublineage of the delta variant, with the only known difference being an additional mutation, K417N, in the virus’ spike protein, the protein that allows it to infect healthy cells.

...The WHO shared with Reuters that “For the moment, this variant does not seem to be common, currently accounting for only a small fraction of the delta sequences.”

Yet, “Delta and other circulating variants of concern remain a higher public health risk, as they have demonstrated increases in transmission,” the WHO added.

Furthermore, since India has labeled this variant a “variant of concern,” the country’s SARS-CoV-2 Consortium on Genomics (INSACOG), which is made up of 28 laboratories dedicated to whole genome sequencing of the SARS-CoV-2 virus and its evolving variants, continues to follow the evolution of delta plus.

...While a new SARS-CoV-2 variant is inevitably concerning, there are no immediate indicators to suggest that delta plus is more infectious or dangerous than the other variants...

https://www.medicalnewstoday.com/articles/delta-plus-variant-of-sars-cov-2-how-d...

COVID-19 vaccination may be stemming evolution of “fitter” SARS-CoV-2 variants
Sally Robertson | Jul 6 2021

...in 25 countries where more than 25% of the population was fully vaccinated, they found that the decline in lineage diversity was indeed correlated with increased rates of mass vaccination.

...Furthermore, the decline in lineage diversity was coupled with increased dominance of the B.1.1.7 (alpha), B.1.1.617 (delta) and P.1 (gamma) variants of concern, suggesting that these variants may be “fitter” SARS-CoV-2 lineages.

..."This study presents the first known evidence that COVID-19 vaccines are fundamentally restricting the evolutionary and antigenic escape pathways accessible to SARS-CoV-2,” says Soundararajan and colleagues.

"The societal benefit of mass vaccination may consequently go far beyond the widely reported mitigation of SARS-CoV-2 infection risk and amelioration of community transmission, to include the stemming of rampant viral evolution,” they conclude.

https://www.news-medical.net/news/20210706/COVID-19-vaccination-may-be-stemming-...

----------------------------------------------------

Soundararajan V, et al. COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance. medRxiv, 2021. doi: https://doi.org/10.1101/2021.07.01.21259833, https://www.medrxiv.org/content/10.1101/2021.07.01.21259833v1

Abstract
Variants of SARS-CoV-2 are evolving under a combination of immune selective pressure in infected hosts and natural genetic drift, raising a global alarm regarding the durability of COVID-19 vaccines. Here, we conducted longitudinal analysis over 1.8 million SARS-CoV-2 genomes from 183 countries or territories to capture vaccination-associated viral evolutionary patterns. To augment this macroscale analysis, we performed viral genome sequencing in 23 vaccine breakthrough COVID-19 patients and 30 unvaccinated COVID-19 patients for whom we also conducted machine-augmented curation of the electronic health records (EHRs). Strikingly, we find the diversity of the SARS-CoV-2 lineages is declining at the country-level with increased rate of mass vaccination (n = 25 countries...). Given that the COVID-19 vaccines leverage B-cell and T-cell epitopes, analysis of mutation rates shows neutralizing B-cell epitopes to be particularly more mutated than comparable amino acid clusters (4.3-fold...). Prospective validation of these macroscale evolutionary patterns using clinically annotated SARS-CoV-2 whole genome sequences confirms that vaccine breakthrough patients indeed harbor viruses with significantly lower diversity in known B cell epitopes compared to unvaccinated COVID-19 patients (2.3-fold...). Incidentally, in these study cohorts, vaccinated breakthrough patients also displayed fewer COVID-associated complications and pre-existing conditions relative to unvaccinated COVID-19 patients. This study presents the first known evidence that COVID-19 vaccines are fundamentally restricting the evolutionary and antigenic escape pathways accessible to SARS-CoV-2. The societal benefit of mass vaccination may consequently go far beyond the widely reported mitigation of SARS-CoV-2 infection risk and amelioration of community transmission, to include stemming of rampant viral evolution.

Eric Topol @EricTopol | Jul 6, 2021, 8:19 PM :
...Case report of 2 people with C. difficile treated with fecal transplant who also had covid and improved (and they've started a clinical trial)
Image-scan of letter, highlighted ( https://twitter.com/EricTopol/status/1412566875767119872/photo/1 )
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Jarosław Biliński et al. 2021. Rapid resolution of COVID-19 after faecal microbiota transplantation (Letter). (BMJ) Gut http://dx.doi.org/10.1136/gutjnl-2021-325010 https://gut.bmj.com/content/early/2021/06/25/gutjnl-2021-325010

Coronavirus vaccines may not work in some people. It’s because of their underlying conditions.
Early research shows that 15 to 80 percent of people with certain medical conditions, such as specific blood cancers or organ transplants, are generating few antibodies after receiving coronavirus vaccines.
Ariana Eunjung Cha | May 18, 2021

Federal health officials’ decision l...to rescind almost all masking and distancing recommendations for those who are fully vaccinated only added to the sense of fear, isolation and confusion for those with immune issues...the change might leave them with less — not more — freedom as their risk of infection grows as more of their neighbors and co-workers ditch their masks.

...The good news...is that scientists are prepared with some potential solutions, such as boosters or high-dose shots. They just need to scramble to study them so they can offer them as soon as possible.

...Numerous potential solutions for the immunocompromised are being debated. One simple idea is to provide one or more booster shots for those with weak responses. So an immunocompromised person might get three doses of the Pfizer-BioNTech or Moderna vaccine, instead of two.

Another possibility is to try preventive doses of lab-produced antibody proteins known as monoclonal antibodies that until now have been mostly used as treatments for those who are infected with the coronavirus.

One thing doctors don’t recommend is for vaccinated people to get antibody tests. First of all, no one knows what levels of antibodies are effective against the virus. Moreover, Kim emphasized that antibodies are only one part of the immune system and that it’s possible that the vaccines have activated other, more difficult-to-measure components.

...Many physicians urge immunocompromised patients to continue to practice social distancing and take other precautions...

https://www.washingtonpost.com/health/2021/05/18/immunocompromised-coronavirus-v...

C. S. Pramesh et al. 2021. Choosing Wisely for COVID-19: ten evidence-based recommendations for patients and physicians (Correspondence) Nature Medicine (5 July 2021) https://www.nature.com/articles/s41591-021-01439-x

...For the general public
1. Do use well-fitting masks appropriately, whenever in public...
2. Do avoid crowded places, especially while indoors...
3. Do get tested if you have symptoms of COVID-19, and isolate yourself at home if symptoms are mild...
4. Do seek medical help if you have difficulty breathing, or your oxygen saturation drops to less than 92%...
5. Do get vaccinated as soon as you are eligible, and even if you have had COVID-19 in the past...

For healthcare workers
6. Do not prescribe unproven or ineffective therapies for COVID-19...
7. Do not use drugs like remdesivir and tocilizumab except in specific circumstances where they may be of use...
8. Do use steroids prudently only in patients with hypoxia, and monitor blood sugar levels to keep them in the normal range...
9. Do not routinely perform investigations that do not guide treatment, such as CT scans and inflammatory biomarkers...
10. Do not ignore the management of critical non–COVID-19 diseases during the pandemic...

Table 1. ( https://www.nature.com/articles/s41591-021-01439-x/tables/1 )

Men may experience worse outcomes from #COVID19 than women due, in part, to a metabolic molecule that influences immune and inflammatory responses, according to a new study of 39 patients in Science Signaling:

Yuping Cai et al. 2021. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 06 Jul 2021: Vol. 14, Issue 690, eabf8483. DOI: 10.1126/scisignal.abf8483 https://stke.sciencemag.org/content/14/690/eabf8483

Sex-specific metabolism and COVID-19
Males and females have different immune responses to SARS-CoV-2 infection, with male sex being a risk factor for mortality, particularly among older individuals. Cai et al. performed metabolomics analysis of serum from COVID-19 patients and uninfected health care workers and identified 17 metabolites that were associated with the disease. However, in male COVID-19 patients only, the amount of the tryptophan metabolite kynurenic acid (KA) correlated with age, inflammation, and disease outcome. KA inhibits glutamate release, and glutamate abundance was reduced in patients who deteriorated. Together, these findings indicate that KA is associated with sex-specific differences in immune responses to COVID-19, suggesting that it might be targeted in male patients.

"Vitamin D insufficiency or deficiency is associated with 2.3-3.6 times higher risk of severe SARS-CoV-2 infection necessitating hospital admission. However, there is no association between vitamin D deficiency and excess mortality in COVID-19."

Vitamin D reduces hospital risk (13:58)
Dr. John Campbell | Jul 5, 2021

Vitamin D deficiency is associated with higher hospitalisation risk from COVID-19: a retrospective case-control study (June 2021)...

https://www.youtube.com/watch?v=_W8tWkT2BC0
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Edward B Jude et al. 2021. Vitamin D deficiency is associated with higher hospitalisation risk from COVID-19: a retrospective case-control study. The Journal of Clinical Endocrinology & Metabolism, dgab439, Published: 17 June 2021. https://doi.org/10.1210/clinem/dgab439 https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab439/6303537

Accepted manuscript

Abstract
CONTEXT
One of the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is postulated to be vitamin D deficiency. To understand better the role of vitamin D deficiency in the disease course of COVID-19, we undertook a retrospective case-control study in the North West of England (NWE).

OBJECTIVE
To examine whether hospitalisation with COVID-19 is more prevalent in individuals with lower vitamin D levels.

METHODS
The study included individuals with results of serum 25-hydroxyvitamin D (25OHD) between 1 st April 2020 and 29th January 2021. Patients were recruited from two districts in NWE. The last 25(OH)D level in the previous 12 months was categorised as ‘deficient’ if less than 25 nmol/L and ‘insufficient’ if 25-50 nmol/L.

RESULTS
80,670 participants were entered into the study. Of these, 1,808 were admitted to hospital with COVID-19, of whom 670 died. In a primary cohort, median serum 25(OH)D in participants who were not hospitalised with COVID-19 was 50.0 ... nmol/L versus 35.0 ... nmol/L in those admitted with COVID-19 ... There were similar findings in a validation cohort (median serum 25(OH)D 47.1 ... nmol/L in non-hospitalised versus 33.0 ...nmol/L in hospitalised patients). Age-, sex- and seasonal variation-adjusted odds ratios for hospital admission were 2.3-2.4 times higher among participants with serum 25(OH)D less than 50 nmol/L, compared to those with normal serum 25(OH)D levels, without any excess mortality risk.

CONCLUSIONS
Vitamin D deficiency is associated with higher risk of COVID-19 hospitalisation. Widespread measurement of serum 25(OH)D and treating any unmasked insufficiency or deficiency through testing may reduce this risk.

...Conclusions: Vitamin D insufficiency or deficiency is associated with 2.3-3.6 times higher risk of severe SARS-CoV-2 infection necessitating hospital admission. However, there is no association between vitamin D deficiency and excess mortality in COVID-19. Urgent action is required to address the high prevalence of vitamin D deficiency that increases COVID-19-related morbidity. Future studies should also investigate any potential role of vitamin D sufficiency in the prevention of SARS-CoV-2 infection.

UK

Deepti Gurdasani et al. 2021. Mass infection is not an option: we must do more to protect our young. (Correspondence) The Lancet. Published:July 07, 2021DOI:https://doi.org/10.1016/S0140-6736(21)01589-0 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01589-0/fullt...

...(Govt:) vaccines have “broken the link between infection and mortality”. On July 19, 2021—branded as Freedom Day—almost all restrictions are set to end. We believe this decision is dangerous and premature...

First, unmitigated transmission will disproportionately affect unvaccinated children and young people who have already suffered greatly...

Second, high rates of transmission in schools and in children will lead to significant educational disruption, a problem not addressed by abandoning isolation of exposed children (which is done on the basis of imperfect daily rapid tests)...

Third, preliminary modelling data suggest the government's strategy provides fertile ground for the emergence of vaccine-resistant variants...

Fourth, this strategy will have a significant impact on health services and exhausted health-care staff who have not yet recovered from previous infection waves...

Fifth, as deprived communities are more exposed to and more at risk from COVID-19, these policies will continue to disproportionately affect the most vulnerable and marginalised, deepening inequalities...

Instead, the government should delay complete re-opening until everyone, including adolescents, have been offered vaccination and uptake is high, and until mitigation measures, especially adequate ventilation (through investment in CO2 monitors and air filtration devices) and spacing (eg, by reducing class sizes), are in place in schools. Until then, public health measures must include those called for by WHO (universal mask wearing in indoor spaces, even for those vaccinated), the Scientific Advisory Group for Emergencies (SAGE), the US Centers for Disease Control and Prevention (ventilation and air filtration), and Independent SAGE (effective border quarantine; test, trace isolate, and support). This will ensure that everyone is protected and make it much less likely that we will need further restrictions or lockdowns in the autumn.

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EMERGENCY SUMMIT AGAINST MASS INFECTION
THURSDAY 8th JULY, 10:00 am
https://www.johnsnowmemo.com/summitdeclaration.html

PRESS CONFERENCE
https://www.youtube.com/watch?v=VYTyi2pFXxk

Zain Chagla (MD infectious diseases McMaster U) @zchagla | 4:30 PM · Jul 7, 2021:

Public Health Ontario Report on Vaccinated "breakthrough cases" - obviously time lags but still good data

Spoiler: Vaccines work
Fully vaccinated adults make up 0.2% of hosp, 0.2% of ICU, and 0.3% of deaths from symptomatic COVID-19

This is a disease of the unvaccinated

Image--graph https://twitter.com/zchagla/status/1412871645690273803/photo/1

-------------------------------------------------

ENHANCED EPIDEMIOLOGICAL SUMMARY
Confirmed Cases of COVID-19 Following Vaccination in Ontario: December 14, 2020 to June 26, 2021
Public Health Ontario
https://www.publichealthontario.ca/-/media/documents/ncov/epi/covid-19-epi-confi...

The world’s reported Covid death toll passes four million.
Daniel E. Slotnik | July 8, 2021

...It took nine months for the virus to claim one million lives, and the pace has quickened since then. The second million were lost in three and a half months, the third in three months, and the fourth in about two and a half months. The number of daily reported deaths has declined recently.

Those are officially reported figures, which are widely believed to undercount pandemic-related deaths...

https://www.nytimes.com/2021/07/08/world/covid-death-toll-four-million.html

Eric Topol (Scripps MD scientist) @EricTopol | 9:10 AM · Jul 8, 2021:
By the end of June, the US vaccination campaign prevented 279,000 deaths and up to 1.25 million additional hospitalizations, and prevented the Alpha variant from leading to a significant 4th wave, according to @commonwealthfnd new report

---------------------------------------------

Deaths and Hospitalizations Averted by Rapid U.S. Vaccination Rollout
The Commonwealth Fund | July 7, 2021
https://www.commonwealthfund.org/publications/issue-briefs/2021/jul/deaths-and-h...

In Ontario, Feb-June 2021, elevation in risk associated with N501Y-positive variants of concern (VOC) --principally alpha (B.1.1.7 UK), beta (B.1.351 S Africa) and gamma (P.1 Brazil) variants--was
74% (62-86%) for hospitalization;
138% (105-176%) for ICU admission; and
83% (57-114%) for death.

Increases with delta (B.1.617.2 India) variant were even larger:
105% (80-133%) for hospitalization;
241% (163-344%) for ICU admission; and
121% (57-211%) for death.

David Fisman and Ashleigh Tuite. 2021. Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada, February to June, 2021. MedRxiv July 7, 2021. https://www.medrxiv.org/content/10.1101/2021.07.05.21260050v1 https://www.medrxiv.org/content/10.1101/2021.07.05.21260050v1

This article is a preprint and has not been certified by peer review.

Abstract
The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (principally alpha, beta and gamma variants), and then by the delta variant. We demonstrate that these emerging VOCs were associated with an increase in virulence, as measured by risk of hospitalization, intensive care unit admission, and death. Compared to non-VOC SARS-CoV-2 strains, and adjusting for comorbidity, age and sex of cases, and temporal trends, the elevation in risk associated with N501Y-positive variants was 74% (62-86%) for hospitalization; 138% (105-176%) for ICU admission; and 83% (57-114%) for death. Increases with delta variant were even larger: 105% (80-133%) for hospitalization; 241% (163-344%) for ICU admission; and 121% (57-211%) for death. The progressive increase in transmissibility and virulence of SARS-CoV-2 variants will result in a significantly larger, and more deadly, pandemic.

The Lambda virus variant is worrying scientists after taking over in Peru. Limited evidence says it's more infectious, but still vulnerable to vaccines.
Marianne Guenot | July 8, 2021

The Lambda coronavirus variant has been targeted for more study by the WHO.
It carries an unusual set of mutations and became dominant in Peru, where it was first identified.
But there is not enough information to know whether it is more transmissible yet, say experts....

The Lambda variant is in 29 countries, including the US
...most prevalent in Peru, where it made up 81% of all cases in May and June...

'Unusual' mutations could increase transmissibility *

Vaccines seem to remain effective against the Lambda variant
...A study from NYU Grossman School of Medicine** offered more proof that the vaccines still work against Lambda, with some caveats...

Too soon to worry?
(WHO: variant of interest, not (yet) variant of concern)

https://www.businessinsider.com/lambda-variant-emerges-experts-fear-could-spread...
---------------------------------------------------------------

* Mónica L. Acevedo et al. 2021. Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda. MedRxiv (July 1, 2021) https://doi.org/10.1101/2021.06.28.21259673 https://www.medrxiv.org/content/10.1101/2021.06.28.21259673v1.full.pdf

Preprint. Not yet peer-reviewed.

ABSTRACT
Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.

Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.

Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.

Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough
-------------------------------------------------------------

** Takuya Tada et al. 2021. SARS-CoV-2 Lambda Variant Remains Susceptible to Neutralization by mRNA Vaccine-elicited Antibodies and Convalescent Serum. BioRxiv (July 3, 2021)
doi: https://doi.org/10.1101/2021.07.02.450959 https://www.biorxiv.org/content/10.1101/2021.07.02.450959v1

This article is a preprint and has not been certified by peer review.

Abstract

The SARS-CoV-2 lambda variant (lineage C.37) was designated by the World Health Organization as a variant of interest and is currently increasing in prevalence in South American and other countries. The lambda spike protein contains novel mutations within the receptor binding domain (L452Q and F490S) that may contribute to its increased transmissibility and could result in susceptibility to re-infection or a reduction in protection provided by current vaccines. In this study, the infectivity and susceptibility of viruses with the lambda variant spike protein to neutralization by convalescent sera and vaccine-elicited antibodies was tested. Virus with the lambda spike had higher infectivity and was neutralized by convalescent sera and vaccine-elicited antibodies with a relatively minor 2.3-3.3-fold decrease in titer on average. The virus was neutralized by the Regeneron therapeutic monoclonal antibody cocktail with no loss of titer. The results suggest that vaccines in current use will remain protective against the lambda variant and that monoclonal antibody therapy will remain effective.

Citing the Delta Variant, Pfizer Will Pursue Booster Shots and a New Vaccine
Scientists were critical of the announcement, pointing to evidence that the current two-dose regimen is powerfully effective against the coronavirus.
Apoorva Mandavilli | July 8, 2021

Pfizer and BioNTech announced on Thursday that they were developing a version of the coronavirus vaccine that targets Delta, a highly contagious variant that has spread to nearly 100 countries. The companies expect to begin clinical trials of the vaccine in August.

Pfizer and BioNTech also reported promising results from studies of people who received a third dose of the original vaccine. A booster given six months after the second dose of the vaccine increases the potency of antibodies against the original virus and the Beta variant by five- to tenfold, the companies said.

Vaccine efficacy may decline six months after immunization, the companies said in a news release, and booster doses may be needed to fend off virus variants.

The data have not been published, nor peer-reviewed. The vaccine makers said they expected to submit their findings to the Food and Drug Administration in the coming weeks, a step toward gaining authorization for booster shots.

...Generally, Americans who have been fully vaccinated do not need a booster shot at this time, the F.D.A. and the Centers for Disease Control and Prevention said in a joint statement.

Health officials in Israel have estimated that full vaccination with the Pfizer-BioNTech offers only 64 percent efficacy against the Delta variant. (Efficacy against the original virus is greater than 90 percent.)

But Israel’s estimates have been contradicted by a number of other studies finding that the vaccine is highly effective at preventing infection — against all variants. One recent study showed, for example, that the mRNA vaccines like Pfizer’s trigger a persistent immune reaction in the body that may protect against the coronavirus for years....

...(Dr. Céline Gounder, an infectious disease specialist at Bellevue Hospital Center in New York) “If we’re worried about variants...our best protection is to get the rest of the world vaccinated, not to hoard more doses to give third doses of mRNA vaccines to people here in the U.S.”

https://www.nytimes.com/2021/07/08/health/pfizer-booster-delta-variant.html

England

Bill Comeau (statistician U W Ont) @Billius27 | 11:11 PM · Jul 8, 2021
Startling estimates of the impact of #vaccines in England.
These charts are on a log scale!...

- from PHE vaccine surveillance report, week 27
Image--graph, vaxxed v unvaxxed, infection, mortality, prevalence, England Jan-Jul 2021
( https://twitter.com/Billius27/status/1413335012443820032/photo/1 )

Old vaccines for COVID-19: Tetanus, diphtheria show promise
Yasemin Nicola Sakay | June 20, 2021

...Those who had received a tetanus booster were half as likely to develop severe COVID-19, and those who had received a diphtheria booster were 54% less likely...

...Despite diphtheria, tetanus, and pertussis being caused by bacteria and COVID-19 by a virus, multiple studies have demonstrated heterologous immunity

...older adults who have received a diphtheria or tetanus vaccine booster within the past 10 years may have a lower risk of severe COVID-19.

The researchers found “no significant differences in the likelihood to test positive or have a severe case” with the pertussis vaccine, and they noted the small sample size.

...“One possible mechanism for this would be that these vaccines instill cross-reactive immunity, i.e., that they ready the immune response for a SARS-CoV-2 infection, perhaps through protein sequence similarities between the pathogens.”...

https://www.medicalnewstoday.com/articles/old-vaccines-for-covid-19-tetanus-diph...

------------------------------------------------------

Jennifer Monereo-Sánchez et al. 2021. Vaccination history for diphtheria and tetanus is associated with less severe COVID-19. MedRxiv (June 12,2021) doi: https://doi.org/10.1101/2021.06.09.21257809 https://www.medrxiv.org/content/10.1101/2021.06.09.21257809v1

This article is a preprint and has not been peer-reviewed

ABSTRACT
Background
COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity. While some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. It has been hypothesized that previous vaccinations for other pathogens, in particular tetanus, may provide protection against severe COVID-19.

Methods
We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) the outcome of this test, and 3) whether they developed severe COVID-19.

Results
We found that individuals with registered diphtheria or tetanus vaccinations were less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria OR=0.46, ...; tetanus OR=0.50, ...).

Discussion
These results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.

Study reveals children and youth had highest rates of SARS-CoV-2 infection in Canada
before third wave
COVID-19 Task Force | July 6, 2021

Ron Gravel, Director at Statistics Canada and lead on the project. “The study includes data from all 10 provinces and three territories, people from both rural and urban areas, and Canadians with varied health status.”

...“The overall seroprevalence of SARS-CoV-2 antibodies was 3.4% among children and youth 1 to 19 years of age between November and April 2021,” explains Mr. Gravel. “As vaccines had not yet been distributed to this age group at the time of the survey, nearly all of these children and youth had antibodies due to a previous infection. In comparison, 2.9% of Canadians 20 to 59 years of age, and 1.4% of Canadians 60 years of age and older, were found to have antibodies due to a past infection.” Estimates for the Canadian population 60 years of age and older do not include those living in an institutional setting, such as a retirement home or in a long-term care setting...

Visible minority Canadians more affected by the virus
Canadians belonging to visible minorities had a higher proportion of antibodies acquired through past infection (4.3%) compared to other Canadians (2.1%). This contributed to a higher overall SARS-CoV-2 antibody seroprevalence among visible minorities (4.8%) compared to other Canadians (3.3%).

...“About one in three (30.3%) Canadians who had antibodies due to a SARS-CoV-2 infection had never taken a PCR test – a nasal or throat swab test for an active infection,” reveals Mr. Gravel. Among those, 3 out of 4, (76.6%) indicated that it was because they never had symptoms.

Antibody seroprevalence varied across the country
Before the third wave, the percentage of Canadians with antibodies (the seroprevalence) due to a previous infection was highest in Alberta (4.0%), followed by Quebec (3.2%), Saskatchewan (2.9%), Ontario (2.5%), Manitoba (2.4%) and British Columbia (1.6%). The Atlantic Provinces had only 0.5% seroprevalence due to past infection, while the number of residents in the Territories to have antibodies due to a past infection was too low to produce a reliable statistical estimate....

Made-in-Canada testing technology
...dried blood spot (DBS) kits, also known as finger prick tests

Products
(See tables at bottom of webpage.)

Upcoming Townhall for more information
The CITF is hosting a townhall, in collaboration with Statistics Canada, open to all Canadians...more detailed...

The event will take place on July 15, from noon to 1 p.m. EDT. The event is free and will be held via Zoom webinar. Click here to register. ( https://ccrsolutions.zoom.us/webinar/register/WN_Q5_ZQdPdT6SXEsmAy3fI_A )
...

https://www.covid19immunitytaskforce.ca/study-reveals-children-and-youth-had-hig...

Michelle Sholzberg (hematology oncology St Michael's Hospital) @sholzberg | 2:02 PM · Jul 9, 2021:
https://twitter.com/sholzberg/status/1413559148726427649
Final results of the RAPID trial now pub'd*
RAPID was an open-label trial that randomly assigned hospitalized ward patients with COVID-19 and elevated D-dimer levels to therapeutic or prophylactic heparin...
-----------------------------------------------
Michelle Sholzberg et al. 2021. Heparin for Moderately Ill Patients with Covid-19. MedRxiv (July 9, 2021) doi: https://doi.org/10.1101/2021.07.08.21259351 https://www.medrxiv.org/content/10.1101/2021.07.08.21259351v2

This article is a preprint and has not been certified by peer review

Abstract
Background Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death.

Methods We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat.

Results At 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69...). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22...). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59...). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52...).

Conclusions In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days.

COVID-19 and lasting erectile dysfunction: Here’s what we know
Rong-Gong Lin II | July 6, 2021

...Dr. Ryan Berglund, a urologist at the Cleveland Clinic. At the moment, there’s primarily anecdotal evidence, and “we don’t know the scale of the problem at this point.” ... it ha(s) not been prove(n) that COVID-19 causes erectile dysfunction.

...Dr. Emmanuele Jannini, professor of endocrinology and medical sexology at the University of Rome Tor Vergata,... could be a symptom of “long COVID”...suspected the risk was higher in patients who suffered from pneumonia accompanying COVID-19, which triggers inflammation of the blood vessels — specifically, endothelial cells that line the body’s blood vessels.

When those blood vessels and the rest of the cardiovascular system are harmed, it can trigger erectile dysfunction, Jannini said. He suspects that when a coronavirus infection leads to erectile dysfunction, it can last long after the initial bout with COVID-19 has passed.

...Here, in short, are several of the reasons COVID-19 could contribute to persisting erectile dysfunction or otherwise impair male sexual health:

Pneumonia from COVID-19 causes blood vessels to become inflamed
Pneumonia caused by COVID-19 harms blood oxygen levels
COVID-19 may damage the cells that produce testosterone
Lacking a sense of smell may affect arousal
Depression and anxiety from the pandemic may contribute
More study is needed...

https://www.latimes.com/california/story/2021-07-06/can-covid-19-cause-lasting-e...

Guidance for COVID-19 Prevention in Kindergarten (K)-12 Schools
CDC | Updated July 9, 2021

...Summary of Recent Changes

Added information on offering and promoting COVID-19 vaccination.

Updated to emphasize the need for localities to monitor community transmission, vaccination coverage, screening testing, and occurrence of outbreaks to guide decisions on the level of layered prevention strategies.

Revised to emphasize the COVID-19 prevention strategies most important for in-person learning for K-12 schools.

Added language on the importance of offering in-person learning, regardless of whether all of the prevention strategies can be implemented at the school.

For example, because of the importance of in-person learning, schools where not everyone is fully vaccinated should implement physical distancing to the extent possible within their structures (in addition to masking and other prevention strategies), but should not exclude students from in-person learning to keep a minimum distance requirement.

Updated to align with guidance for fully vaccinated people.
Updated to align with current mask guidance.
In general, people do not need to wear masks when outdoors.
Added language on safety and health protections for workers in K-12 schools.

https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/k-12-guida...

World Health Organization (WHO) WHO | 4:17 PM · Jul 8, 2021
The #COVID19 situation globally is very dangerous with high levels of transmission driven by 4️⃣ major factors:
1️⃣ virus variants
2️⃣ increased social mixing and mobility of people
3️⃣ inappropriate use of public health & social measures
4️⃣ vaccine inequity
- Dr @mvankerkhove

2:13 ( https://twitter.com/WHO/status/1413230703605600259 )

Public Health England (PHE):
Good news-- 1. "secondary attack rates have fallen but remain higher for Delta than for Alpha."
2. case fatality rate for Delta continues to lessen

OTOH, mutations continue-- "New data is included on the prevalence of mutations of predicted antigenic significance in the global dataset – there is an increase in mutations of predicted antigenic significance over time, even outside the designated variants of concern and variants under investigation."
-------------------------------------------------------

Eric Topol @EricTopol | 9:41 AM · Jul 9, 2021:
The new @PHE_Uk report today
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attac... *

Good to see Delta's (B.1.617.2, first reported in India) secondary attack rate (an indicator of transmissibility) has continued to drop and now similar to that of Alpha (B.1.117, first reported in UK)

(See last three columns in)
Image- table transmission ( https://twitter.com/EricTopol/status/1413493440751431687/photo/1 )

Also the case fatality rate for Delta continues to lessen, 0.2% compared with 1.9% Alpha, predominantly due to younger people getting infected. There are NO data to suggest Delta is more deadly than prior virus strains.

(See last column--due to younger immune systems, older people vaxxed, more effective treatments, --and hopefully, changes in Delta variant.)
Image-table mortality ( https://twitter.com/EricTopol/status/1413537810296950786/photo/1 )

-------------------------------------------------

* SARS-CoV-2 variants of concern and variants under investigation in England
Technical briefing 18
PHE | 9 July 2021 (56 p)
This briefing provides an update on previous briefings up to 25 June 2021

Summary
...Principal changes and findings this week are: 
Delta variant accounted for approximately 99% of sequenced and 97% genotyped cases from 27 June to 3 July 2021 

the number of genome sequence results available is maintained but the coverage has fallen with the increasing case numbers

secondary attack rates have fallen but remain higher for Delta than for Alpha.
New data is included on the prevalence of mutations of predicted antigenic significance in the global dataset – there is an increase in mutations of predicted antigenic significance over time, even outside the designated variants of concern and variants under investigation

additional spike mutations are occurring on Delta but are present at relatively low frequencies both in the UK and global datasets

there is an increase in PCR positivity in the SIREN (national healthcare worker) cohort and a small but increasing number of possible reinfections

two new variants in monitoring have been designated (B.1.619 and B.1.629, Table 1) ...

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attac...

__________________________________________
Thread ( https://twitter.com/dgurdasani1/status/1413583199687659522 )

Deepti Gurdasani (Queen Mary U London) @dgurdasani1 | 3:37 PM · Jul 9, 2021
Predictable but worrying data showing continuing rises in daily case numbers and a
increases in hospitalisations. We're now seeing 500 daily hospitalisations, and
some NHS trusts are already having to cancel routine operations & delay cancer care.
Image-graphs cases, deaths, hospitalization UK Jan-Jul 2021
https://twitter.com/dgurdasani1/status/1413583199687659522/photo/1

The spread among school-age children and young adults is frankly quite shocking. The almost vertical line here says it all.
Image-by age group
https://twitter.com/dgurdasani1/status/1413583204271919111/photo/1

Most outbreaks are in educational settings - rapid increases week on week. Large numbers of outbreaks in both primary and secondary schools.
Image-bar graph,#cases by setting
https://twitter.com/dgurdasani1/status/1413583218993995777/photo/1

...The most common activity reported by those testing positive prior to symptom onset was attending an educational or childcare setting.
Image- bar graph activities
https://twitter.com/dgurdasani1/status/1413583218993995777/photo/1
.
.
.

Oh, yikesie. Winter is coming...esp. for the unvaxxed Americans...

Eric Topol @EricTopol | 11:39 AM · Jul 9, 2021
The US covid fatalities, which have steadily declined for months,
are starting to climb again.

% Delta shown, and trends in death rates for 3 countries

Fully vaccinated adults
US 59%
UK 62%
Israel 85%

(graph at right shows timing for total population)
Image ( https://twitter.com/EricTopol/status/1413523131784851462/photo/1 )

Eric Topol @EricTopol | 5:09 PM · Jul 10, 2021:
#VaccinesWork vs Delta
A summary table I put together for vaccine protection from the Delta variant from publications and preprints.
5 vaccines—neutralizing antibodies well above threshold (lab studies)
3 vaccines—clinical effectiveness
will update as more data becomes available
Image- table ( https://twitter.com/EricTopol/status/1413968623815647235/photo/1 )

Eric Topol (Scripps MD scientist) @EricTopol | 10:54 PM · Jul 10, 2021:
Delta in Arkansas and Missouri now is starting to look like Alpha in Michigan a few months ago

Image-maps ( https://twitter.com/EricTopol/status/1414055508865032192/photo/1 )
-------------------------------------------

Michael Cole (MD lawyer) @WhiteRabbitWB
Replying to @EricTopol
I don't think it looks good. The effective R {number people infected by one person} is climbing through 3.4 ( compare with say 2.5 for the original strain). Unless vaccination rates improve our model suggests a peak of 350,000 cases a day in US in about November.

Image-graph projections Oct 22, 2021-March 2022
https://twitter.com/WhiteRabbitWB/status/1414089665238290435/photo/1

____________________________________

Eric Feigl-Ding @DrEricDing | 2:41 PM · Jul 10, 2021
Bad trend—Netherlands reports a near vertical more than 800% increase in new #COVID19 cases in 1 week. Greece and Spain nearly matching that surge. WHO now reports over 2 dozen countries with “near vertical” sharp rises in cases—mostly #DeltaVariant. Pandemic “Act 2” has begun.

Image-graph, cases by country, May 1- July 10, 2021
https://twitter.com/DrEricDing/status/1413931514954489860/photo/1

------------------------------------------------

Eric Feigl-Ding @DrEricDing | 2:56 PM · Jul 10, 2021

3) How does Netherlands, Greece, Spain compare in vaccinated %? All 3 countries ~ 40% fully vaccinated. Not that low relative to the world or rest of Europe. UK is 50% vaccinated and it’s still seeing hospitalizations & deaths rise. Keep vaccinating—#DeltaVariant coming.

Image-bar graph % vaxx by country
https://twitter.com/DrEricDing/status/1413935263970205703/photo/1

https://www.mediaite.com/tv/anthony-fauci-its-horrifying-to-see-cpac-audience-ch...
Anthony Fauci: ‘It’s Horrifying’ to See CPAC Audience Cheer for America Not Being More Vaccinated

What would CPACers be thinking and saying if this was the polio era???

>138 Molly3028: Like Vaxxed Murdoch and other Fox vaxees' disinformation campaign... Like shouting fire in a theater... :(
________________________________________

Topol's table from yesterday updated with preprint for India vaxx, Bharat Biotech *

Eric Topol @EricTopol | 12:07 PM · Jul 11, 2021
Updating #VaccinesWork vs Delta
4 vaccines with clinical effectiveness data
https://medrxiv.org/content/10.1101/2021.06.30.21259439v1 * via @sayan94194742
Image-table vaxxes agst Delta
https://twitter.com/EricTopol/status/1413968623815647235/photo/1
----------------------------------------------------
* Raches Ella et al. 2021. Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a, double-blind, randomised, controlled phase 3 trial. MedRxiv (July 2, 2021). doi: https://doi.org/10.1101/2021.06.30.21259439 https://www.medrxiv.org/content/10.1101/2021.06.30.21259439v1

This article is a preprint and has not been peer-reviewed

ABSTRACT
Background We report the clinical efficacy against COVID-19 infection of BBV152, a whole-virion inactivated SARS-CoV-2 vaccine formulated with a Toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG).

Methods We did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18–98 years) randomised 1:1 using a computer-generated randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory-confirmed symptomatic COVID-19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in sub-groups for age (18–under 60 years and 60 years or older) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots.

Findings Between November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0·77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77·8% ... Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93·4% ... Efficacy against asymptomatic COVID-19 was 63·6% .... BBV152 conferred 65·2% ... protection against the SARS-CoV-2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported.

Interpretation BBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID-19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines.

Dr. Abraar Karan (Stanford) @AbraarKaran | 12:37 PM · Jul 11, 2021:
1/ New CDC report on #covid19 outbreak caused by Delta variant in Oklahoma gym {below}, causing 47 cases.
Notably- over 90% of cases were among *unvaccinated or partially vaccinated* people.
Very high household secondary attack rate (53%)

2/ Risk factors here:
-larger groups
-inconsistent mask use
-poor ventilation
-low vaccination rates
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Kendra Dougherty et al. 2021. SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility — Oklahoma, April–May 2021. U.S. Dept of Health and Human Services Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report Early Release / Vol. 70 July 9, 2021 (5p). https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7028e2-H.pdf

Summary
What is already known about this topic? The SARS-CoV-2 B.1.617.2 (Delta) variant emerged in India and is currently widespread. Evidence suggests that it is potentially more transmissible than other variants.

What is added by this report?
During April 15–May 3, 2021, 47 COVID-19 cases were linked to a gymnastics facility, including 21 laboratory-confirmed B.1.617.2 cases and 26 epidemiologically linked cases. The overall facility and household attack rates were 20% and 53%, respectively.

What are the implications for public health practice?The B.1.617.2 variant is highly transmissible in indoor sports settings and households, which might lead to increased attack rates. Multicomponent prevention strategies including vaccination remain important to reduce the spread of SARS-CoV-2 among persons participating in indoor sports and their contacts.

...Discussion The primary case in this outbreak likely occurred in one or more staff members or gymnasts with undetected SARS-CoV-2 infection during April 1–13, 2021. Review of other potential exposure sources, including gymnastics meets, did not explain the case distribution among cohorts early in the outbreak because a limited number of cohorts participated in meets during this period. Among the 47 outbreak-associated cases, sequencing of virus from the 21 patients with available specimens identified the B.1.617.2 (Delta) variant in all 21. Emerging evidence suggests that attack rates for the B.1.617.2 variant are potentially higher than are those for other variants of concern, including the B.1.1.7 (Alpha) variant ... The 20% attack rate among exposed gymnasts and staff members in this outbreak was consistent with attack rates previously reported among persons in other high-risk activities..., demonstrating that this variant is easily transmissible in high-risk settings with suboptimal adherence to recommended disease control measures. Further, household attack rates in this outbreak (53%) were higher than reported secondary attack rates associated with other SARS-CoV-2 lineages (17%)...

Image-Table 1 ( https://twitter.com/AbraarKaran/status/1414262636984684549/photo/1 )

Eric Topol @EricTopol | 1:22 PM · Jul 11, 2021:
The Delta hit to the US is now extending from cases to hospitalizations,
13 states with >65 margd:% Delta prevalence now with ≥25% increase of hospitalizations over past 14 days

Image-table 13 states cases, hospitalized
https://twitter.com/EricTopol/status/1414274021777035266/photo/1

The Delta Variant: How this new strain of COVID is in a league of it's own (23:05)
60 Minutes Australia | Jul 11, 2021
https://www.youtube.com/watch?v=7NPKlXM9MTg

True?

BREAKING: 25% of the world's population is at least partially vaccinated against COVID-19
- BNO Newsroom @BNODesk | 3:15 PM · Jul 11, 2021

Pregnancy and COVID-19
In a worldwide study of 2100 pregnant women, those who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus. The investigation involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 countries between April and August, 2020. Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, pre-eclampsia, and admission to the intensive care unit or intubation. Of mothers who tested positive for the disease, 11·5% of their babies also tested positive. Although other studies have looked at COVID-19's effects on pregnant women, this study is among the first to have a concurrent control group with which to compare outcomes, said the lead author.

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C. Mary Healy, MD. 2021. COVID-19 in Pregnant Women and Their Newborn Infants (Editorial).
JAMA Pediatr. Published online April 22, 2021. doi:10.1001/jamapediatrics.2021.1046
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2779183

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José Villar, MD et al. 2021. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 InfectionThe INTERCOVID Multinational Cohort Study (Original Investigation). JAMA Pediatr. Published online April 22, 2021. doi:10.1001/jamapediatrics.2021.1050 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2779182

Conclusions and Relevance In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Graph: Cases correlate with school closings/openings in Ontario.
Ontario repeating July Step 3 (almost fully opened) and Sept school reopening, only this time most people vaxxed...fingers crossed!

Bill Comeau Crush the Curve (statistician) @Billius27 | 12:31 PM · Jul 11, 2021
Weekly look at Ontario smoothed cases with major events.
https://twitter.com/Billius27/status/1414261159146967045/photo/1

Canada to donate almost 18 million surplus AstraZeneca doses to low- and middle-income countries
Federal government also announces $10 million donation-matching campaign with UNICEF
Peter Zimonjic · CBC News · Posted: Jul 12, 2021
https://www.cbc.ca/news/politics/covax-donations-astrazeneca-surplus-1.6099072

"...the prevalence of Long COVID is around 1 in 7 people at three months from the infection, and it is most common in working-age adults, but also occurs in other age groups, including children..."

Nisreen A. Alwan . 2021. The teachings of Long COVID. Communications Medicine volume 1, Article number: 15 (2021) https://www.nature.com/articles/s43856-021-00016-0

Long COVID is prolonged illness resulting from SARS-CoV-2 infection. Its serious implications for individuals and society have been missing from public communication and pandemic policy. Here, I draw on my lived experience, research, and advocacy work with Long COVID and reflect on the lessons learnt.

Long COVID is the state of not recovering several weeks following acute infection with SARS-CoV-2, whether tested or not1. It is a patient-made2 umbrella term for this condition, which may involve multiple pathologies. The underlying mechanisms are still largely unknown, but hypotheses include inflammatory or autoimmune processes, organ damage and scarring, hypercoagulability, endothelial damage, or even persistent viral protein in the body3,4. Based on the UK Office for National Statistics (ONS) estimates, the prevalence of Long COVID is around 1 in 7 people at three months from the infection, and it is most common in working-age adults, but also occurs in other age groups, including children5. More recent ONS figures indicate that there are 376,000 people in the UK who have had Long COVID for at least one year6. It has a wide range of symptoms, but the most common are exhaustion, breathlessness, muscle aches, cognitive dysfunction, including poor memory and difficulty concentrating, headache, palpitations, dizziness and chest tightness or heaviness. The nature of the symptoms is mostly relapsing, resulting in significant dysfunction and limitations in a relatively large proportion of sufferers6,7.

“It seemed nobody had thought about the enormous implications of chronic disease as a result of letting SARS-CoV-2 spread through the community, assuming it would all be fine for those classed as non-vulnerable.” ...

French rush to get vaccinated after president’s warning
CONSTANTIN GOUVY and ANGELA CHARLTON | July 13, 2021.

...President Emmanuel Macron...also announced that special COVID-19 passes will be required starting in early August to enter restaurants and shopping malls and to get on trains and planes. ...

...1.3 million people signed up for injections after Macron gave a televised address Monday night. It was a daily record since France rolled out coronavirus vaccines in December. People under age 35 made up most of the new appointments...

Macron said vaccination would be obligatory for all health care workers by Sept. 15, and he held out the possibility of extending the requirement to others. Around 41% of the French population has been fully vaccinated, though the pace of shots being delivered has waned as summer vacations approached.

...Some people said they’re now getting vaccinated because Macron also announced that France will start charging money for some virus tests, which up to now have all been free for anyone in French territory.

To get the COVID pass that will soon be required in all restaurants, people must have proof of vaccination or recent virus infection, or a negative test from the last 48 hours.

...Health Minister Olivier Veran defended the new rule, saying, “The question is: It’s lockdown or the health pass.”

...More than 111,000 people with the virus have died in France.

https://apnews.com/article/europe-business-lifestyle-health-travel-1d10271c4f161...

https://www.mediaite.com/tv/ingraham-calls-durbin-a-fossil-and-a-windbag-after-h...
Ingraham Calls Durbin a ‘Fossil’ and a ‘Windbag’ After He Slams Her ‘Irresponsible’ Anti-Vax Comments

Do the prime-time personalities on Fox News not realize that they are endangering the well-being and lives of Trump cult followers who they profess to care about???

FDA Warns About Johnson & Johnson COVID Vaccine and Guillain-Barré Syndrome Risk—Here's What That Means
Of the 100 preliminary reports of Guillain-Barré syndrome, 95 were serious.
Colleen Murphy | July 13, 2021

What is Guillain-Barré syndrome?
Why is the vaccine causing an increased risk of Guillain-Barré syndrome?
How long after the COVID vaccine do Guillain-Barré syndrome symptoms develop?
When should you see a doctor if you have symptoms of Guillain-Barré syndrome following a COVID vaccine?
How is Guillain-Barré syndrome diagnosed?
How is Guillain-Barré syndrome treated?

Should the risk of Guillain-Barré syndrome prevent you from getting vaccinated?
The short answer here: No. "The FDA has evaluated the available information for the Janssen COVID-19 Vaccine and continues to find the known and potential benefits clearly outweigh the known and potential risks," the agency said...

https://www.health.com/condition/infectious-diseases/coronavirus/johnson-and-joh...

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Updated:

(7p) FACT SHEET FOR RECIPIENTS AND CAREGIVERS
EMERGENCY USE AUTHORIZATION (EUA) OF THE JANSSEN COVID-19 VACCINE TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) IN INDIVIDUALS 18 YEARS OF AGE AND OLDER

...Guillain Barré SyndromeGuillain Barré syndrome (a neurological disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis) has occurred in some people who have received the Janssen COVID-19 Vaccine. In most of these people, symptoms began within 42 days following receipt of the Janssen COVID-19 Vaccine. The chance of having this occur is very low. You should seek medical attention right away if you develop any of the following symptoms after receiving the Janssen COVID-19 Vaccine:
•Weakness or tingling sensations, especially in the legs or arms, that’s worsening and spreading to other parts of the body
•Difficulty walking
•Difficulty with facial movements, including speaking, chewing, or swallowing
•Double vision or inability to move eyes
•Difficulty with bladder control or bowel function...

https://www.fda.gov/media/146305/download

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Johnson & Johnson Statement on COVID-19 Vaccine (7/12)
https://www.jnj.com/johnson-johnson-july-12-statement-on-covid-19-vaccine

Eric Topol @EricTopol | 11:16 PM · Jul 13, 2021:
The Delta variant impact in Arkansas (US leading edge) is resembling that of the UK's more with each passing day.
Cases/100,000 here. Similar pattern for hospitalizations and deaths, too.
http://outbreak.info

Image-graphs UK and Arkansas
https://twitter.com/EricTopol/status/1415148244141678593/photo/1

>37 margd: CONTD.

Dorothee Bienzle ET AL. 2023. Risk Factors for SARS-CoV-2 Infection and Illness in Cats and Dogs. Emerg Infect Dis. 2022 Jun;28(6):1154-1162.
doi: 10.3201/eid2806.220423. https://pubmed.ncbi.nlm.nih.gov/35608925/

Abstract
We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% ... of swab specimens from dogs and 7.7% ... from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners' beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% ...; in shelter samples, 9.3% ... Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill.