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March 19th, 2020 – Schools, Children, Vaccines, Variants, and More.

Hello,

Another week in the Covid pandemic has passed. Case counts in the U.S. appear to be reaching a plateau. Unfortunately, case counts in several European countries are increasing (Italy, France, Germany, Denmark). Meanwhile, several interesting developments occurred this week on multiple fronts. 

As always if you were forwarded this newsletter and would like to receive it weekly, you may register for free  here  as well as view previous issues.

Be Safe,

Sam


1) School And Children

This was the first week of the Learn EM Survey. It is a survey of schools and their experience with temperature checks of children and adults. The survey is open to all schools or school districts and is aimed at providing evidence for the lack of utility of temperature screening in asymptomatic children and adults. To date, approximately 145,000 temperature measurements of children and 28,000 adults have been reported with zero cases of covid detected and only 2 elevated temperatures detected. The survey includes a majority of pre-school and kindergarten age children. A more detailed analysis will be reported once the survey is closed. If you are a teacher or administrator for a school or district, you may report your data here. The information is not traced back to individual schools and not released to any other parties. 

In other school related news, the journal Lancet published a study examining COVID cases and transmission in primary schools in the U.K.. The study examined swabs and blood samples from more than 6700 students and 4600 staff obtained between June and December, 2020. They found approximately 11% of children and 15% of staff were positive for antibodies at the start of the summer term, which was equivalent to community levels. They also found approximately 5% of students and staff became positive during the school year. They concluded that infection rates in primary schools were low and that “seropositivity (positive antibodies for COVID) was not associated with school attendance during lockdown or staff contact with students ”

Also, last week a study was published in the journal Clinical Infectious Disease, examining COVID transmission rates in multiple school districts in Massachusetts. Schools were divided into those requiring at least 3 feet of distancing vs those requiring at least 6 feet. All districts required mask use. Over 500,000 students and 99,000 staff were included. The study concluded that “lower physical distancing policies can be adopted in school settings with masking mandates without negatively impacting student or staff safety.”

The CDC is reported to be evaluating if 3 feet instead of 6 feet can be safely recommended for schools. An interesting editorial on the topic appeared in The NY Times

Lastly,  Moderna announced it has begun a phase 2/3 trial of its vaccine in children. The trial is enrolling children in the U.S. and Canada and is operating in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) and the Biomedical Advanced Research and Development Authority (BARDA)


2) Vaccines 

A study from the Icahn School of Medicine at Mount Sinai, New York was published in the New England Journal of Medicine last week. It details the antibody response of 110 people after a single dose of the Moderna or Pfizer vaccine. 43 out of the 110 people had previously recovered from a COVID infection. They found that people with prior infection had a vigorous immune response to a single dose, showing rapid increase of antibody levels, and peaking far higher than those without prior infection. They also found that the antibody response in those with prior infection did not significantly change after receiving a second dose. Though small, this study confirms the findings of multiple previous antibody studies showing only one dose of vaccine is necessary in patients who have recovered. It remains unclear if those who have recovered require a vaccine at all. 

Another study in the New England Journal of Medicine examined the ability of the Astra Zeneca vaccine to protect against mild or moderate cases of COVID caused by the B1351 variant (South Africa). It reported that the vaccine had no efficacy against preventing mild to moderate disease. There were no cases of severe COVID in the study so no conclusions can be drawn about the vaccine’s ability to protect against hospitalization or death (what we care about most). Though the study examined serum from over 2000 people, only 42 total cases of COVID occurred in any participants, making any conclusions drawn from it preliminary and in need of further study.

A third study from the New England Journal of Medicine examined antibodies in the serum of patients who received the Moderna vaccine. The antibodies were tested against the United Kingdom (the B.1.1.7 lineage), South Africa (the B.1.351 lineage), Brazil (the P.1 lineage), and California (the B.1.427/B.1.429 lineage) variants. The study found the vaccine to be effective against the B117 but have reduced efficacy against the South African, Brazil, and California variants. Though disappointing, this study does not tell us how the vaccine performs in actual patients infected with these variants. We have seen numerous similar antibody studies published. Though helpful, we still require further study of actual cases in people.

A study in Clinical Infectious Disease reported a decrease in asymptomatic COVID in people who received either the Pfizer or Moderna vaccine. This is good news and suggests that those who are vaccinated are less likely to transmit disease. The actual decrease was unfortunately rather small in this study. Asymptomatic unvaccinated people had a 3.2% positive test rate while vaccinated people had a 1.4% positive test rate.  

Meanwhile, this past week brought the suspension of Astra Zeneca vaccine administration in 13 European countries as the European Medicines Agency examined approximately 37 reports of deep venous thrombosis or pulmonary embolism (blood clots) occurring in people who received the vaccine. Though the WHO immediately advised against the suspension noting no connection between the vaccine and the cases, the European Medicines Agency ultimately reached a similar conclusion yesterday, calling the “rare” occurrence a “possible link” that is outweighed by the vaccine benefit.

Lastly, China has approved a fourth vaccine developed in country. For details of each of the current vaccines being produced worldwide, see The NY Times tracker. It now also details each US state’s current vaccine eligibility requirements.


3) Variants 

The CDC is now tracking SARS-CoV-2 variants and publishing its data online. The system had three levels of classification. 

There are currently 5 variants of concern circulating in the U.S. : B.1.1.7 (UK) , B.1.351 (South Africa), P.1 (Brazil), and B.1.427 and B.1.429  (California) .  None are listed as variants of high consequence.


4) Long COVID

Peristaltic symptoms post COVID infection, unofficially termed long COVID, are now referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). A study in Nature Medicine examined the results of self reporting of symptoms from 4000 people infected with COVID, in an attempt to better define PASC. They found:

  • 13% have symptoms longer than 28 days
  • 4.5% had symptoms longer than 8 weeks
  • 2.3% has symptoms longer than 12 weeks

They also found that PASC was more likely in older patients with a higher body mass index (BMI) , in females, and in those who experience more than 5 symptoms. 

Another study, published online, examined 44 people with PASC who received either  the Pfizer of Astra Zeneca vaccine. They found no adverse outcomes, no worsening of symptoms, and a small number who reported an improvement in symptoms. Thought small, this study suggests that people with persistent symptoms after COVID infection can safely receive vaccination and may show an improvement in symptoms. 


5) Treatments

A study from the U.K. , published online, examined over 5000 patients hospitalized for COVID who received high titer convalescent plasma as treatment, in comparison to a similar size placebo group. This treatment consists of plasma that is donated by people who have recovered from COVID and still have high antibody levels against the virus. It has been used under FDA authorization as a potential therapy since early on in the pandemic. Unfortunately, this study found it to be of no benefit in reducing mortality or progression to mechanical ventilation (worsening breathing requiring use of a ventilator).


6) Race and Ethnicity

The CDC is now publishing a weekly data review, encapsulating multiple findings of the U.S. pandemic experience. Last week, the review examined how the risks for COVID-19 illness, hospitalization, and death differ by race and ethnicity. They reported:

  • American Indian and Alaska Native people were 3.7 times more likely than non-Hispanic white people to be hospitalized and 2.4 times more likely to die from COVID-19 infection.
  • Black or African American people were 2.9 times more likely than non-Hispanic white people to be hospitalized and 1.9 times more likely to die from COVID-19 infection.
  • Hispanic and Latino people were 3.1 times more likely than non-Hispanic white people to be hospitalized and 2.3 times more likely to die from COVID-19 infection.

7) Reinfection

A study published in the journal Lancet reported data obtained from over 4 million people living in Denmark who were tested for COVID using the national free PCR testing campaigns. The study authors examined test results of individuals during the two waves in Denmark and had several interesting findings:

  • 2.2% tested positive during the first wave.
  • 3.3% tested positive during the second wave.
  • 0.65% of those who recovered tested positive again during the second wave.

They concluded that previous infection provides 80.5% protection against reinfection. However, that number fell to 47% for those 65 years and older. They also found no evidence for decreasing protection at 3-6 month follow up, or >7 months follow up. This suggests that immunity after recovery is long lasting but less vigorous in the elderly. It also suggests that vaccination may be appropriate for the elderly even if they have recovered from prior infection. The study is limited by the fact that it includes data only from Denmark, which reduces its generalizability to the rest of the world. It also is not able to tell us if behaviors changed after people recovered from infection (did they take more risks?). However, it does add valuable data on the rate of reinfection and how it changes with age.

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