This week is the one year anniversary of the WHO declaration of COVID-19 as a worldwide pandemic. It is also a significant point for us as many fronts in the battle against COVID-19 have shown significant improvement. Cases in most countries continue to decline (Italy is a notable exception) and vaccination numbers continue to increase. This week’s newsletter is devoted to a wider review of “Where we are today”. I look forward to the day when I can safely announce this COVID newsletter has seen its final issue. We are certainly closer today than ever.
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1) Learn EM School Survey
Though many of you are reading this newsletter late in the pandemic, it began as a method to communicate, educate, and update a number of schools that have relied on Learn EM to provide practical COVID advice. Recently, several schools asked about the utility of continuing to perform temperature screening. There is little published literature on the practice, but it remains a recommendation from many state health departments and school organizations. This week, we launched the Learn EM School Survey to collect data on the practice in hope of demonstrating that resources are better utilized elsewhere, but we need your help. If you work at a school, please consider completing the survey.If you know someone who works at a school, please consider forwarding the link. It is also posted at the top of the Learn EM webpage. Results are published anonymously and will be available for all to view online.
- Many are asking about the safety of vaccines, specifically regarding possible effects on fertility. There is no evidence that any of the currently approved vaccines interfere with fertility. If the question comes up in conversation, here are some helpful resources:
- American College of Obstetricians and Gynecologists (ACOG) “Medical Experts Continue to Assert that COVID Vaccines Do Not Impact Fertility“
- CDC “Those who are trying to become pregnant do not need to avoid pregnancy after COVID-19 vaccination. There is no evidence that any of the COVID-19 vaccines affect future fertility.“
- Web MD “Why COVID Vaccines are Falsely Linked to Infertility“
- University of Alabama (UAB) “Addressing fertility questions and concerns with the COVID-19 vaccine“
- University of Chicago Medical Center “The mRNA COVID-19 vaccine and pregnancy: What you need to know if you’re pregnant, trying to get pregnant, or breastfeeding“
- Henry Ford Health System “Will Getting The COVID-19 Vaccine Affect My Fertility?“
- Bharat Biotech, manufacturer of India’s COVID-19 vaccine COVAXIN, released an interim summary of its phase 1-3 trials. The announcement notes the vaccine has an 81% efficacy. The study data given shows 25,800 adult participants in the trial, half of whom received the vaccine. At the time of the announcement, there were 43 cases of COVID, 36 occurring in the placebo group and 7 in the vaccine group. The study will continue until it achieves its goal of 130 COVID cases. A separate study published in January found that two dose of the COVAXIN vaccine was effective against the B117 variant in serum samples obtained from vaccinated patients.
- A US based company, Novavax, is continuing its study of its own vaccine. It reported in January that testing in the U.K revealed 89.3% efficacy (half of cases were B117). They also published results of their Phase 2 trial in South Africa where the vaccine showed a 51% efficacy in non-HIV patients (over 90% B1351).
- A U.K. study of healthcare workers shows that a single dose of the Pfizer vaccine was 75% effective in preventing illness AND preventing asymptomatic infection. This adds to the evidence showing that current vaccines are effective in preventing illness AND transmission.
- Another U.K. study published in the journal Lancet examined over 17,000 participants who received the AstraZeneca vaccine. They found that participants who received two standard doses, 12 weeks apart, had a higher vaccine efficacy (81.3%) than those who received it 6 weeks apart (55.1%), supporting the U.K.’s policy to vaccinate as many people as possible with the first dose and delay the second dose.
- The European Commission granted emergency authorization to Johnson & Johnson for distribution of its Janssen vaccine.
- There is a new vaccine tracker available from the London School of Hygiene & Tropical Medicine. It details the myriad of vaccines in study, the evidence supporting each, and the global locations of ongoing trials. A discussion of the website appeared in the journal Lancet last week.
- Lastly, a new site named Dr. B – Standby list for leftover COVID vaccines now provides a method for people to register online to receive vaccine doses that may otherwise go to waste. A registrant agrees to be notified within 6 hours of a dose expiration time. The website accumulates data from local pharmacies and other vaccine providers and ranks patients by risk factors, taking into account local regulations. It is currently available in the U.S.. Further information about the venture based in NY is available in this NYT review “Covid-19 Vaccines: Dr. B Website Will Match You With Leftover Doses“
3) Are Those Who Have Recovered Immune From All Variants?
We have discussed this before (see #2 and #4), but there continues to be debate about the ability of recovered patients to fight off re-infection by COVID variants. An interesting piece of data showed up in the Novavax phase 2 trial publication. During their study, they found that patients who had previously been infected with the original strain, had the same rate of becoming infected with the B1351 variant as those without prior infection. The actual numbers come from 29 cases of COVID in the placebo group. The risk of being infected with the B1351 variant was 5.3% in the naive (never infected) group vs. 5.2% in the previously infected group. Although these numbers are small, this report suggests that infection with the original strain of SARS-CoV-2 does not provide any protection against the B1351 variant. Despite that, cases continue to decline in South Africa where the B1351 variant is responsible for almost all cases. This finding in the Novavax trial suggests that recovered patients still require vaccination but a larger patient data set is necessary.
Another study published in Cell Host & Microbe demonstrates that B117 is effectively neutralized by the serum of people who have recovered from infection by the original SARS-CoV-2 strain or those who have been vaccinated with the Moderna or Novavax vaccines.
4) Medications To Treat (or Not) COVID
Since the beginning of the pandemic, many therapies have been recommended to treat COVID-19 infection. Most of these required large scale trials to be proven ineffective. Though this is not an exhaustive list, here are some recent interesting studies. The NY Times does a good job maintaining a COVID Treatment list and the status of each medication.
- This week Merck announced preliminary findings from a phase 2a trial of a new therapy for COVID, molnupiravir. The drug is still in trial but this announcement came as the drug met one of its secondary end points (not the primary benefit they are studying but something else they were following). The announcement stated “At day 5, there was a reduction in positive viral culture in subjects who received molnupiravir (all doses) compared to placebo: 0% (0/47) for molnupiravir and 24% (6/25) for placebo.” That is promising and definitely worthy of more study. But more interesting to know are answers to patient related outcomes like: Does the drug prevent symptoms, hospitalizations, or death? These are likely the primary endpoints of the study. We look forward to hearing more when the studies are completed.
- A study in JAMA titled “Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19” randomized 476 patients to receive ivermectin for treatment of COVID. A 5 day course was prescribed and no significant change was seen in the treatment group. They concluded Ivermectin was not beneficial in the treatment of COVID-19. Additionally, the FDA published a webpage titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” warning that it is not approved for use in COVID-19. Lastly Merck, the manufacturers of Ivermectin, made a similar announcement in January, 2021 as well. It is approved for treatment of parasitic worm infections in humans and animals. The medication concentrations for humans and animals are different and not interchangeable.
- An article in the journal Lancet studied azithromycin in 2265 participants with COVID, split into two groups: those over age 65 and those over age 50 with one comorbidity. They found no benefit from azithromycin. Though it is an antibiotic with known effects against bacteria, there was a suggestion early in the pandemic that it might have antiviral or anti-inflammatory effects. No such effect was demonstrated in this study.
- Vitamin C and High Dose Zinc were studied in a JAMA article published in February, 2021. Patients were randomized to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg vit C), both agents, or none. 214 patients were studied. In this small population, no significant reduction in symptoms was seen.
- A study published in the journal Lancet in February studied hydroxychloroquine with and without azithromycin in non-hospitalized patients. The study included 218 patients and concluded “HCQ and HCQ/AZ are not effective therapies for outpatient treatment of SARV-CoV-2 infection.” This adds to list of studies showing no improvement from hydroxychloroquine in the treatment of COVID.
5) COVID Restrictions
Houston, TX became the first city to report all major COVID variants. Meanwhile, Texas is one of a growing list of states that are reducing or eliminating COVID restrictions. There is a good summary here. Individual State Departments of Health remain the best source for this information.
This week the CDC eased restrictions on people who have completed vaccination. These guidelines unfortunately do not apply to those who are unvaccinated but have recovered from infection. The new guidelines state:
- You can gather indoors with fully vaccinated people without wearing a mask.
- You can gather indoors with unvaccinated people from one other household (for example, visiting with relatives who all live together) without masks, unless any of those people or anyone they live with has an increased risk for severe illness from COVID-19 .
- If you’ve been around someone who has COVID-19, you do not need to stay away from others or get tested unless you have symptoms. However, if you live in a group setting (like a correctional or detention facility or group home) and are around someone who has COVID-19, you should still stay away from others for 14 days and get tested, even if you don’t have symptoms.
Also this week, CMS (Centers for Medicare & Medicaid Services) updated its Nursing Home Guidance with new recommendations to safely expand visitation options. “Facilities should allow responsible indoor visitation at all times and for all residents, regardless of vaccination status of the resident, or visitor, unless certain scenarios arise that would limit visitation”, The scenarios, given by CMS, that would limit visitation include:
- Unvaccinated residents, if the COVID-19 county positivity rate is greater than 10 percent and less than 70 percent of residents in the facility are fully vaccinated
- Residents with confirmed COVID-19 infection, whether vaccinated or unvaccinated, until they have met the criteria to discontinue transmission-based precautions
- Residents in quarantine, whether vaccinated or unvaccinated, until they have met criteria for release from quarantine
Also, the CMS recommendation emphasizes that “compassionate care visits should be allowed at all times, regardless of a resident’s vaccination status, the county’s COVID-19 positivity rate, or an outbreak. Compassionate care visits include visits for a resident whose health has sharply declined or is experiencing a significant change in circumstances.”
6) Children and COVID
An interesting study by the CDC was published last week. It studied left over serum samples drawn from children, between May-September 2020, in Mississippi. The state reported 8993 confirmed and probable cases of COVID in children during that time period. However, serum samples showed an increasing percent of positive samples, from 2.5% in may to 16.3% in September. Taking the data from the 1603 samples, the authors extrapolate that by September, over 100,000 children could have been infected, instead of the 8993 cases reported in Mississippi. If true, this study suggests were are far closer to herd immunity than our current confirmed infection rates demonstrate.
Another study published in JAMA last week aimed to answer the question “What is the extent of neurologic involvement in US hospitalized children and adolescents with coronavirus disease 2019 (COVID-19)?” Out of 1695 case of children under 21 hospitalized for COVID or multi-system inflammatory syndrome (MISC), they found:
- 22% (365) had neurologic involvement
- 43 cases of life-threatening neurologic disorders were identified
- 11 died
- 17 survived with new neurologic deficits
They concluded “In this study, many children and adolescents hospitalized for COVID-19 or multi-system inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neuro-developmental outcomes are unknown.”
Lastly, an article appeared this week in the journal Pediatrics, summarizing data from the New York City public schools COVID testing campaign. It examines the results of testing performed between October 9 and December 18, 2020. The data includes over 234,000 persons tested in 1594 New York City schools. There were 986 positive tests, giving a case positivity rate of 0.4%. This prevalence was similar to or less than the community levels for all weeks in the study. The study concluded “We found that in-person learning in New York City public schools was not associated with increased prevalence or incidence overall of COVID-19 infection compared with the general community.”
7) Adults and COVID
A study published last week in JAMA, titled “Outcomes and Mortality Among Adults Hospitalized With COVID-19 at US Medical Centers”. It studied the Vizient database which includes over 650 academic centers in 47 U.S. states. They found 192550 hospitalizations for COVID-19 and noted the following:
- 55593 (28.9%) were admitted to the ICU
- 26221 (13.6%) died during the initial hospitalization
- Mortality increased with age, and ICU admission
- 18-29 : 1.4%
- > 80 : 26.6%
- ICU admission : 27.8%
- Overall mortality decreased over time, starting at 22.1% in March 2020 and ending at 6.5% in August 2020.
- Median hospital stay was 6 days for non-ICU patients and 15 days for ICU patients.
In this study group of admitted patients, obesity was the third most common comorbidity (27.4%) behind hypertension (61.5%) and diabetes (38.4%). This is similar to findings from another study published by the CDC this week showing that “Obesity was a risk factor for hospitalization and death, particularly among adults aged < 65 years.”
Another large, international, multi-center study was published in the journal Anaesthesia. Its authors sought to determine the optimal time to undergo elective surgery after recovering from COVID. After examining 3127 patient records, they determined the following mortality risk for surgery after diagnosis with COVID:
- 9.1% for surgery within 2 weeks (104 of 1,138)
- 6.9% for surgery 3–4 weeks (32 of 461)
- 5.5% for surgery 5–6 weeks (18 of 326)
- 2.0% for surgery 7 or more weeks (24 of 1,202)
After 7 weeks, the risk neared the general surgical risk for non-covid patients, quoted to be 1.5%. They concluded “Where possible, surgery should be delayed for at least 7 weeks following SARS‐CoV‐2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.” This recommendation assumes that the risk of waiting (delaying surgery) does not present a higher mortality. It is an excellent study that will help inform important conversations with surgeons regarding the best timeline for surgery.
8) Athletes and COVID
A study published in JAMA Cardiology examined 789 professional athletes with COVID in the North American professional sports leagues including Major League Soccer (MLS), Major League Baseball (MLB), the National Hockey League (NHL), the National Football League (NFL), and the men’s and women’s National Basketball Associations (NBA and WNBA, respectively). All COVID positive athletes were screened with Troponin testing (blood test), electrocardiography (ECG), and resting echocardiography after recovery. If abnormal, they underwent cardiac magnetic resonance imaging (MRI) and/or stress echocardiography. 3.8% had an abnormal screen and 0.6% were ultimately diagnosed with a heart condition (myocarditis or pericarditis) that temporarily prevented them from return to play. There were no adverse events for anyone who returned to play after a normal screen. The authors concluded “While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved”.