The past 7 days have brought good news for the US along with some unwelcome news about variants and vaccines. Below is a summary of items I have found helpful, and answers to questions posed at Learn EM. If you have a question you would like to see answered in a newsletter, you may submit it here.
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1) The state of the COVID Pandemic
The CDC has begun releasing a “COVID Tracker Weekly Review” every Friday, which I have found helpful. Highlights from last week include:
- The 7 day moving average of daily new cases has decreased by 10% compared to the previous week.
- The latest virus typing shows a predominance of the B117 (UK) variant at 44.7%. Multiple other variants are present in the US but at much lower levels.
- The 7 day average test volume (PCR) in the US increased slightly to 1,189,820 while the test positivity rate for the nation decreased to 5.2%. These are positive changes.
- As of April 22, 2021, one in three people in the United States over the age of 18 years are fully vaccinated and more than half of U.S. adults have received at least one dose. This is also good news.
- Hospitalizations due to COVID continue to increase slightly, up 1.6%. However, deaths continue to decrease, down 3.7%.
All this is very positive for the US. Meanwhile, across the globe cases are reaching critical levels. India is in the midst of one of the world’s worst outbreaks almost overtaking Brazil. Most surprising is the sudden increase in India compared to other countries. There have been heartbreaking stories of dire conditions and critical shortages of oxygen and supplies throughout India. Our World In Data has done a good job displaying the data and allowing viewers to manipulate graphs to compare raw numbers of cases, hospitalizations, and deaths. The results show the full scale of the devastation world wide. At a time of seeming reprieve in the US with cases falling and vaccine rates increasing, our hearts and prayers are with our fellow humans as they experience great tragedy.
2) Is it possible to be infected with COVID after vaccination and to what severity?
This is a good question. Up until this week, studies have shown that COVID vaccines have excellent efficacy for protection against hospitalization and death. Both the Pfizer and Moderna vaccines had efficacies of >90% for prevention of severe disease and both had no hospitalizations or deaths due to COVID-19 in their initial trials. Rates of COVID-19 in vaccinated healthcare workers have been reported as low as 0.05% (see item 6, March 26th newsletter) with most being asymptomatic.
This week the CDC released information which unfortunately changes the landscape.
The CDC published a report of a COVID-19 outbreak in a skilled nursing facility in Kentucky. The facility had 90% of its residents and 52% of its employees vaccinated with the Pfizer vaccine. Most had been vaccinated in early January and February though a small number were less than two weeks from their second dose. Routine screening of employees detected a positive case in a symptomatic worker on March 1. At that point, daily screening of all residents and workers began. Unfortunately, this led to a total of 26 residents and 20 employees becoming infected. Of those infected, 18 residents and 5 employees were fully vaccinated (>14 days since second dose). A total of three residents died. One of the people who died was fully vaccinated. Another was a patient who had recovered from COVID 300 days earlier.
Further investigation revealed that the COVID-19 strain causing this outbreak new, containing several mutations found in other variants. Specifically, it contained the E484K mutation found in the B1351 (South Africa) and P1 (Brazil) variants.
What did we learn?
- Vaccination was associated with decreased likelihood of infection and symptomatic illness
- Vaccination was not 100% protective. In fact, 25.4% of vaccinated residents and 7.1% of vaccinated employees were infected.
- Previous infection was not protective. 4 symptomatic reinfections occurred in one resident and three employees. One of these employees was also fully vaccinated. The reinfected resident died.
- Unvaccinated residents had a 3 fold chance of being infected, and unvaccinated employees had a 4 fold chance of being infected.
- Vaccination efficacy (protection) against symptomatic illness in this outbreak was 86.5% among residents and 87.1% among employees.
- Vaccination efficacy against hospitalization was 94% among residents.
What does all this mean?
A couple of conclusions can be drawn from these numbers. First, the vaccines are effective even against strains with mutations similar to the South Africa and Brazil variants. Second, being unvaccinated and living in a nursing home puts someone at high risk of death from COVID-19. Six residents in the facility were unvaccinated (for unknown reasons). Four of them were hospitalized and two died. Lastly, though vaccine efficacy is still good, it is not 100%. One person who was fully vaccinated died of COVID-19. We don’t known anything about this person’s health history, but this is still a sobering occurrence.
Should I panic?
No. This report includes a small number of patients, with unknown medical histories. As variants continue to spread throughout the US, vaccination still gives us the best chance against being infected. Though infection after vaccination is possible, the majority of people remain well protected after being fully vaccinated. If you are unvaccinated, now is the time to seek vaccination.
Is there other evidence for infection after vaccination?
Yes. The CDC is tracking voluntary reporting of COVID-19 after vaccination. These are termed “break through” cases and, to date, there have been 7,157 cases with over 89 million people vaccinated. That places the risk of contracting COVID-19 after vaccination at less than 1 in 10,000. The actual number of people who have breakthrough cases is expected to be higher since the reporting is voluntary, but the point is clear. Yes it is possible to become infected after vaccination, and it is rare.
We do not yet have enough information to predict who is at highest risk for having a breakthrough case. However, the most current CDC data shows:
- 31% have been asymptomatic
- 7% have required hospitalization
- 1% (88 people) died but the CDC states that “11 (13%) of the 88 fatal cases were reported as asymptomatic or not related to COVID-19”, meaning death was not attributable to COVID-19
In the last newsletter, we discussed the current literature regarding immunity after infection. (See item 6, April 8th) Adding to that evidence, a study was published in the journal Lancet detailing the Denmark experience with over 500,000 people undergoing testing during their first and second COVID-19 waves in 2020. They found some interesting patterns:
- Out of 11,068 people who were infected during the first wave, 72 became infected again in the second wave, giving a reinfection rate of 0.65%.
- Protection from reinfection was calculated to be approximately 80.5%, however this occurred during a time when little was known regarding variants and their increased virulence.
- Most interesting was the finding that protection against repeat infection was only 47% in those over age 65
The authors concluded that vaccination was beneficial even in those who recovered from infection, especially in those over age 65.
In a similar study published in the journal Lancet, a large group of healthcare workers in England was followed to determine the rate of reinfection between June 2020 and January 2021, a time when B117 became the predominant variant in the UK. They found that previous infection conferred 84% protection against re-infection, with the protection lasting at least 7 months.
3) Johnson & Johnson Vaccine
The vaccine made by Johnson & Johnson has been cleared for use in the US, once again. Its use was temporarily halted by the FDA and CDC after 6 case reports of clotting associated with low platelets, in some cases leading to death. This past week both organizations released a joint statement allowing use of the vaccine once again with a caveat:
“Women younger than 50 years old should be aware of the rare risk of blood clots with low platelets after vaccination, and that other COVID-19 vaccines are available where this risk has not been seen.”
The warning was recommended after case data was reviewed. The CDC notes that 6.8 million doses of the Johnson and Johnson vaccine have been administered, with a total of 15 cases of thrombosis with thrombocytopenia (TTS) reported to the vaccine adverse events reporting system (VAERS), including the original six cases. All 15 cases occurred in women between the ages of 18 and 59, with a median age of 37. Symptoms onset was between 6 and 15 days after vaccination.
“The two agencies have determined the following:
- Use of the Janssen COVID-19 Vaccine should be resumed in the United States.
- The FDA and CDC have confidence that this vaccine is safe and effective in preventing COVID-19.
- The FDA has determined that the available data show that the vaccine’s known and potential benefits outweigh its known and potential risks in individuals 18 years of age and older.
- At this time, the available data suggest that the chance of TTS occurring is very low, but the FDA and CDC will remain vigilant in continuing to investigate this risk.
- Health care providers administering the vaccine and vaccine recipients or caregivers should review the Janssen COVID-19 Vaccine Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers)external icon and Fact Sheet for Recipients and Caregiversexternal icon, which have been revised to include information about the risk of this syndrome, which has occurred in a very small number of people who have received the Janssen COVID-19 Vaccine.”
Thrombosis with thrombocytopenia (TTS) is the same condition that occurred after the Astra Zeneca vaccination, leading to similar suspension, review, and approval by the European Medicines Agency.
4) Rapid Antigen Tests
We have previously discussed some of the controversy surrounding rapid antigen tests (see item 5, April 8th newsletter). These types of COVID tests are now available without a prescription, for home use. A new study in the journal Lancet Microbe examined seven different rapid antigen tests and concluded that the tests were sufficient to detect the disease in the first week of symptoms, when viral loads are highest.
The seven rapid tests examined included:
- Abbott Panbio COVID-19 Ag Rapid Test
- RapiGEN BIOCREDIT COVID-19 Ag
- Healgen Coronavirus Ag Rapid Test Cassette (Swab)
- Coris BioConcept COVID-19 Ag Respi-Strip
- R-Biopharm RIDA QUICK SARS-CoV-2 Antigen
- nal von minden NADAL COVID-19 Ag Test
- Roche-SD Biosensor SARS-CoV Rapid Antigen Test
5) Inhaled steroids for COVID-19?
A study in the Lancet Respiratory Medicine examined the effects of inhaled steroids (budesonide) on patients with mild covid-19 symptoms. It concluded that “early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19.” However, it is important to note that the study only included people with mild covid symptoms. The effect of the inhaled medication was reduction in symptoms by one day, from 8 to 7 days. People who used the medication also reported less fever events. Though interesting, this study did not include hospitalized or critically ill patients. There is no evidence that this therapy is effective in reducing hospitalizations or death. I look forward to more data on those effects.
6) FDA revokes authorization of a COVID-19 antibody treatment
The FDA has revoked the emergency use authorization granted to Eli Lilly for its antibody medication, Bamlanivimab, stating: “Based on its ongoing analysis of emerging scientific data, specifically the sustained increase of SARS-CoV-2 viral variants that are resistant to bamlanivimab alone resulting in the increased risk for treatment failure, the FDA has determined that the known and potential benefits of bamlanivimab, when administered alone, no longer outweigh the known and potential risks for its authorized use. ”
7) What’s the status of vaccine trials in children?
- Last month, Pfizer began a study of its COVID vaccine in 3 groups of children ages 5 to 11 years, 2 to 5 years, and 6 months to 2 years. The trial will enroll 4,644 children across the US and Europe. Results are expected in the second half of 2021.
- Moderna also began a study in children age 6 months to 12 years last month. The study is based in the US in cooperation with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
8) Are vaccines safe in pregnancy or breastfeeding? Does COVID infection affect pregnancy?
A report in the New England Journal of Medicine published results from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS). The report used data from 35,691 people who stated they were pregnant and received a COVID-19 m-RNA vaccine from December, 2020 to February, 2021. The study findings compared reported events to those reported in studies prior to the COVID-19 pandemic.
They concluded “Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.”
Specifically, there was no increase in miscarriages, preterm births or small size for gestational age diagnoses. In addition, no neonatal deaths were reported.
Additional publications have shown:
- SARS-CoV2 does not appear to be passed through the placenta when mother becomes infected. A study published in JAMA last year showed no signs of the virus in umbilical cord blood, placental tissue, or babies, born to 64 COVID positive mothers.
- Antibodies to SARS-CoV2 after infection are passed from mother to baby. A study published in JAMA Pediatrics in January, 2021 showed that IgG antibodies passed from mother to baby successfully in 72 women with prior COVID infection, providing proof that passive (antibody) immunity can be passed to the baby from mother.
- Antibodies from COVID vaccines can also be passed to newborns through breastfeeding. A study published this month in JAMA showed high levels of IgA and IgG antibodies in breastmilk for 6 weeks after vaccination. These antibodies showed strong neutralizing effects suggesting a protective effect for the newborn. The same study also cites multiple similar studies in women who have recovered from COVID.
All of this is welcome news and adds to the growing body of evidence that babies are protected both in the womb and after delivery when born to mothers who have either recovered from COVID or who have been vaccinated.
Why does this matter? Is COVID-19 really a problem for pregnant patients?
Another study published in JAMA Pediatrics a few days ago examined a total of 706 pregnant women with COVID-19 and compared them to 1424 pregnant women without COVID-19. It included data from 43 institutions in 18 countries, between March and October, 2020. They found that pregnant women with COVID-19 were at higher risk of :
- Preeclampsia / eclampsia – relative risk, 1.76, or 76% increase
- Severe infections – relative risk 3.38 or more than triple the risk
- Intensive care unit admission – relative risk 5.04 or more than 5 x the risk
- Maternal mortality – relative risk 22.3
- Preterm birth – relative risk 1.59
- Medically indicated preterm birth – relative risk 1.97
- Severe neonatal morbidity index – relative risk 2.66
- Severe perinatal morbidity and mortality index – relative risk 2.14
Given the higher risk of multiple complications and the apparent safety of the current m-RNA vaccines, vaccination appears to be the safest option for pregnant women.