The U.S. and most countries around the world continue to have improvements in case counts and deaths. This is very welcome news. As the U.S. continues its push to vaccinate more people, this week’s newsletter brings updates regarding new vaccines, efficacy, and side effects.
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1) Johnson & Johnson Vaccine
The FDA Vaccine Advisory Panel is scheduled to review the Johnson & Johnson “Janssen Ad26.COV2.S” Vaccine during its meeting this morning. The public meeting is broadcast online and is scheduled for 9 am. Links to the broadcast are available on the meeting website. On Wednesday, the FDA published the committee meeting materials. These include 2 documents from the manufacturer, a 118 page briefing document and a 6 page addendum. Additionally, the FDA performed its own review of the manufacturer submitted data and published a 62 page briefing document. Expect a special issue of the Learn EM newsletter with a summary of the FDA briefing document next week. Similar summaries of the FDA documents for the Moderna and Pfizer vaccines were published in the Learn EM newsletter shortly after their approval by the same committee.
2) COVID Testing and the FDA
The COVID testing market continues to grow. In its Feb 23rd update, the FDA summarized the number and types of tests currently available under emergency use authorization (EUA). The list includes:
- 331 total tests currently authorized
- 247 molecular tests and sample collection devices
- 37 molecular tests can be used with home-collected samples
- one molecular prescription at-home test
- 70 antibody tests
- 14 antigen tests
- one antigen prescription at-home test
- one over-the-counter (OTC) at-home antigen test
A complete list of currently authorized tests can be found here. Interestingly, only 1 antigen test has authorization for “screening” of asymptomatic people without known exposure, and it is an at-home test. Also you may be surprised to learn that only 14 molecular tests have the “screening” authorization. The FDA also maintains a list of tests that should no longer be used or distributed which currently includes: 15 antigen tests and 239 antibody tests.
3) Pfizer Vaccine Storage
The FDA is expected to approve Pfizer’s request to store its vaccine in a standard freezer. Pfizer submitted stability data to the FDA on Feb 19th suggesting that the vaccine could be safely stored at standard pharmacy freezer temperatures (-25°C to -15°C or -13°F to 5°F) for up to two weeks. Storage at these temperatures makes vaccine administration at local pharmacies much easier.
4) Refreshed Vaccines and the FDA
On Feb 22nd, the FDA announced newly revised guidelines for vaccine manufacturers seeking to submit updates to vaccines already authorized. This applies to vaccines that may receive an update to better protect against a new variant of Sars-CoV-2. Specifically, the new guidelines forgo the need for traditional clinical studies and instead recommend:
“For clinical data, the guidance recommends that a determination of effectiveness be supported by data from clinical immunogenicity studies, which would compare a recipient’s immune response to virus variants induced by the modified vaccine against the immune response to the authorized vaccine. Manufacturers are also encouraged to study the modified vaccine in both naïve (non-vaccinated) individuals and in individuals previously vaccinated with the authorized vaccine. Additionally, the guidance outlines the FDA’s recommendations for assessments of safety to support an EUA for a modified vaccine. Finally, the guidance states that further discussions will be necessary to decide whether in the future, modified COVID-19 vaccines may
be authorized without the need for clinical studies. “
In addition, on Feb 24th, Moderna announced that it had shipped an updated vaccine, mRNA-1273.351, specifically created for B1351 (South Africa) variant of SARS-CoV-2. The new samples were sent to the National Institute of Health (NIH) for a phase 1 clinical trial. The trial will examine
- A variant-specific booster candidate, mRNA-1273.351 at the 50 µg dose level and lower.
- A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower.
- A third dose of mRNA-1273, the Moderna COVID-19 Vaccine, as a booster at the 50 µg dose level. The Company has already begun dosing this cohort with the booster.
5) Variants and Vaccine Efficacy
Two studies appeared in the New England Journal Of Medicine on Feb 17th. The first study examined the serum of participants in the Moderna phase 1 trial for neutralizing antibody response to B117 (UK) and B1351 (South Africa) variants in addition to the additional Wuhan strain. The study found that antibodies were able to neutralize all of them, but with less efficacy against the newer variants. A second study found similar results for the Pfizer vaccine, also testing serum only. Though these studies add to our understanding of antibody response to variants, both have the same limitation of being laboratory studies not clinical trials in real patients. There are other mechanisms the immune system uses to combat infection (T-cell immunity) which can not be measured in this type of study.
The University of Edinburgh published its data on the experience in Scotland, between Dec 8, 2020 and Feb 15, 2021, with the Pfizer and AstraZeneca vaccines. They noted that vaccination was “linked to substantial reduction in the risk of Covid-19 admissions to Scotland’s hospitals”. After 4 weeks post vaccination, they found an 85% (Pfizer) and 94% (AstraZeneca) reduction in the risk of hospitalization. They also found this benefit remained high, 81%, even for those over age 80. The study period occurred when B117 variant activity was at its peak in the U.K. .Full details of the EAVII project in Scotland can be found here.
Lastly, a study examining the effects of the Pfizer vaccine in healthcare workers in the U.K. was published online in the journal Lancet. The researchers studied workers with a history of infection and those without prior infection. They found the vaccine successfully prevented infection in 72% of workers 21 days after the first dose. That number increased to 86%, 7 days after the second dose. This is good news for healthcare workers. The study was not designed to tell us if vaccinated people can still carry the virus, but it did confirm the vaccine’s effectiveness in preventing illness.
6) Pfizer Vaccine Response In Recovered Patients
A new study, yet to be peer reviewed, was published online. It examined 13 individuals who had recovered from COVID and 19 who had never been infected. Both groups received two doses of the Pfizer vaccine and then had antibody titers performed. The group with prior infection showed a very robust increase in antibody levels after the first dose with minimal change after the second. The group without previous COVID infection showed a small response after the first dose with a much larger increase after the second. Both groups ended with similar antibody levels. This suggests that those who have recovered from COVID may not require a second dose of the vaccine. It is a similar finding to a study that appeared in our Feb 12th newsletter (item 4).
Another study not yet peer reviewed, examined 425 healthcare workers in Greece for antibody levels 14 days after the first dose of the Pfizer vaccine and confirmed appropriate increase in antibodies. They also found a more vigorous response in those who had recovered from infection, showing a much higher antibody titer compared to those who had not been previously infected. Interestingly, they found a smaller increase in antibody titer levels in workers over age 50, with a even lower increase in those over age 60.
7) New Variants
Researchers have published descriptions of two new variants in the U.S.. The variants were reported in California (CAL.20C) and New York (B.1.526). Very little is known about their infectious rates. Preliminary reports note they may be more infectious than the original Wuhan strain but less infectious than the B117 (UK) and B1351 (South Africa) variants. The CDC continues to track known variant cases by state. The New York Times also tracks variant types, detailing the mutations each variant contains. It is important to keep in mind that variants and mutations are common for viruses, especially coronaviruses. Most important is the clinical significance, which tells us how these variants behave in people, if there is an increase in illness severity, and if there is any effect on vaccine efficacy.
8) The Meaning of 95% Efficacy
An interesting editorial appeared in the journal Lancet: Infectious Diseases on Feb 17th, 2021. It clarifies the meaning of published efficacy rates for COVID vaccines. The writer notes that a 95% efficacy rate, commonly quoted for the mRNA vaccines by Pfizer and Moderna, does not mean that out of 100,000 people vaccinated, 5% (5000) will become infected. In the vaccine trials, 1% of the non-vaccinated group became ill with COVID. The vaccine reduced that number by 95%. So the math goes like this instead:
100,000 people x 1% community spread risk of becoming infected (varies by country and community) = 1000 ill COVID patients. If all were vaccinated, that number would drop by 95% which brings us to 50 people ill with COVID.
So, a person’s risk of becoming ill with COVID after vaccination goes from 1% to 0.05%. It is a clarification of a person’s risks in order to educate people that they do not have a 5% risk of getting infected after being vaccinated. It is actually far lower. Conditions that would change the calculation would include working in high risk environments, like healthcare workers, where the chance of contracting the illness would be significantly higher. Furthermore, the approved vaccines prevented all deaths from COVID (100%).
9) Vaccination an Mammography
Radiologists at Moffitt Cancer Center in Tampa, FL are asking patients to schedule mammograms prior to vaccination or wait 4-6 weeks after. The concern is that vaccination (Moderna or Pfizer) can cause swelling of lymph nodes, a common temporary side effect. These can appear on the mammogram as enlarged lymph nodes in the axilla (arm pit) and be mistaken for an early sign of breast cancer resulting in unnecessary biopsies.
10) Schools and COVID
A group from Tulane University published a report from the National Center for Research on Education Access and Choice (REACH) titled “The Effects of School Reopening on COVID-19 Hospitalizations“. The report details the recommendations from REACH to use COVID hospitalizations per 100,000 instead of new cases per 100,000 when determining if schools should reopen. The CDC recently updated its guidelines for schools based on cases per 100,00 (discussed in last week’s newsletter, see item 2). The Tulane group suggests that cases per 100,000 fluctuates and can be effected by school opening as more parents are inclined to have children tested in order to attend school. They reviewed hospitalization data from counties across the U.S. and suggest that this marker is more relevant and represents a better measure of community illness. After completing their review they concluded that it appears safe to reopen schools in counties where there are fewer than 36-44 new COVID-19 hospitalizations per 100,000 people per week. The report suggests that most counties have low enough COVID hospitalization numbers to reopen schools now, and they provide an online spreadsheet allowing the general public to look up their county. They also concluded “We found no evidence that reopening schools in-person or in a hybrid form increased COVID hospitalizations in the 75 percent of counties that had low COVID hospitalization rates during the summer, prior to reopening schools.”