Another busy week of scientific publications brings good news related to vaccinations. In addition, case counts continue to fall nationally, which is also very welcome news. Though total numbers are still high, we welcome any reprieve.
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1) Sputnik V Preliminary Trial Data Published
Preliminary results from a phase 3 trial of the Russian vaccine, Sputnik V, were published in the journal Lancet this week. The trial included 21,977 adults, 16,501 in the treatment group and 5,476 in the placebo group. The population was 61% male, 98.5% white, with 10% age >60. It was conducted from Sep 7 – Nov 24, 2020 in 25 hospitals in Moscow. The study protocol included two shots, a prime dose day one and a booster dose day 21. The published preliminary analysis includes data collected on day 21; the day of the second shot. At that time, the study reported 78 cases of COVID-19 in participants, 16 (0.01%) in the vaccine group and 62 cases in the placebo group (1.3%), with a community wide prevalence of 2%. Based on these cases, the efficacy is reported as 91.6%. Further data analysis showed the efficacy to be >87% in all age groups, with the highest rate (91.8%) in patients >60 yrs old. The safety profile was good with the majority of the trial participants experiencing mild symptoms. There were 4 deaths reported in the first 21 days, 3 in the vaccine group and 1 in the placebo group. No deaths were thought to be related to vaccination. These results are very positive. The full trial data, including follow up through days 28, 42, and 180 has not been published.
2) AstraZeneca Vaccine Second Dose Can Be Delayed
A study from the Lancet in preprint, shows that patients who received the first dose of the AstraZeneca vaccine had persistent elevated levels of antibodies up to three months, with vaccine efficacy of 76%. Most importantly, there were no hospitalizations in the vaccine group after a 21 day waiting period. The study suggests that patients can wait at least 90 days before receiving their second dose. This will be well received by countries seeking to vaccinate people as rapidly as possible, allowing them to maximize the interval between doses in order to reach more people as quickly as possible.
3) AstraZeneca Vaccine Reduces Transmission
Many have been asking if vaccinated patients can still transmit the virus without themselves becoming infected. Until now, the theory has been that this is possible and vaccinated patients should still wear masks and take all precautions. The same study looking at single dose efficacy of the AstraZeneca vaccine from the Lancet in preprint, also tested participants for PCR evidence of infection. They found a 67% reduction positive swabs, suggesting that vaccinated patients are less likely to transmit the virus. The viability of the virus particles is unknown as cultures were not performed.
4) How Long Do Patients Shed Live Virus?
In an attempt to answer this question, a new study from South Korea published in the New England Journal Of Medicine attempted to culture live virus from 21 hospitalized patients infected with COVID-19. SARS-Cov-2 was cultured in 29 of 89 samples. They found the following:
- Median symptom onset to viral clearance in culture was 7 days, with the latest being 12 days.
- Median symptom onset to viral clearance on real-time RT-PCR was 34 days
- Viable virus was identified until 3 days after the resolution of fever in one patient
- Viral culture was positive only in samples with a cycle-threshold value of 28.4 or less
They concluded that findings may be useful in guiding isolation periods for patients with COVID-19. However, they did also state “Given the small sample size, inconsistent timing of sampling, and relatively mild illness of the enrolled patients, our results should be verified in larger and more diverse groups of patients.”
5) One Vaccine Dose For Those Who Have Recovered
Two studies in preprint with the BMJ suggest that patients who have recovered form COVID-19 may not require two doses of a vaccine. The first study compared 109 patients (41 recovered and 68 naive) after receiving either the Pfizer or Moderna vaccine and found that the antibody response of patients who already recovered from COVID-19 was very high. They noted that the antibody levels achieved with once vaccine dose, after infection, were higher than those seen in naive (non-infected patients) even after two vaccines. They suggest one vaccine is sufficient and can free up additional doses for others who have not been infected. The second study investigated health care workers with known history of infection who received either the Pfizer of Moderna vaccine. They also found that those with previous infection demonstrated higher antibody titers after a single dose and suggest that recovered patients can safely be treated with one dose AND should be moved lower on the vaccination priority list.
Both of these studies prove the value of prior infection. It remains unclear if patients who have recovered from COVID-19 require a vaccination at all. As a reminder, a recent publication reported last week, from the National Institute of Health, showed persistent antibody elevation up to 8 months after recovery in this population.
6) How Many People Are Asymptomatic?
A systematic review published in the Annals of Internal Medicine suggests at least one third of patients infected with COVID-19 are asymptomatic. Interestingly, they also concluded “Longitudinal studies suggest that nearly three quarters of persons who receive a positive PCR test result but have no symptoms at the time of testing will remain asymptomatic.”
7) The WHO Changes Recommendations For Vaccinating Pregnant Women
“While pregnancy puts women at higher risk of severe COVID-19, very little data are available to assess vaccine safety in pregnancy. Nevertheless, based on what we know about this kind of vaccine, we don’t have any specific reason to believe there will be specific risks that would outweigh the benefits of vaccination for pregnant women. For this reason, those pregnant women at high risk of exposure to SARS-CoV-2 (e.g. health workers) or who have comorbidities which add to their risk of severe disease, may be vaccinated in consultation with their health care provider.”
This recommendation is more aligned with what the CDC has been recommending.
8) Colchicine For COVID-19
A preprint article examined the effects of colchicine in non-hospitalized patients with COVID-19 in multiple countries, including Canada and the U.S.. They enrolled 4488 PCR positive patients in a randomized control trial of placebo vs colchicine 0.5mg BID for 3 days then once daily for 30 days. Their primary end point was a composite hospitalization or death. They reported (absolute) reduction of 1.4% for the primary end point (4.6% colchicine group and 6% placebo group). They also reported similar decreases in mechanical ventilation and pneumonia. Peer review and formal publication is pending.
9) Allergic Reaction To Pfizer and Moderna Vaccines
Two analyses of anaphylactic reaction to COVID vaccines were published. The first, appearing in JAMA, analyzed 21 cases of anaphylaxis after the first 1.9 million doses of the Pfizer vaccine. They found 21 cases of anaphylaxis with 81% having a documented history of allergies or prior anaphylaxis. Median time to reaction was 13 minutes. The second analysis was published by the CDC, and studied 10 cases of anaphylaxis to the Moderna vaccine after administration of 4 million doses. Similarly, 9 of 10 patients reported a prior history of allergies or anaphylaxis. No deaths occurred in either analysis population.
10) CDC Orders Mandatory Masks On Public Transit
On Jan 29th, the CDC issued an order requiring masks on all public transit in the U.S. , effective Feb 1, 2021. The order excludes children under age 2 and anyone with a disability preventing them from safely wearing a mask.
11) Johnson & Johnson Applies For EUA
Johnson & Johnson, maker of the Janssen COIVD-19 vaccine, has applied for FDA emergency use authorization. The Janssen vaccine is a single dose found to prevent hospitalizations and death. A phase 3 trial showed it to be 72% effective in the US in preventing moderate and severe illness.
12) What Do We Care About Most In A Vaccine
As multiple studies are published for vaccines, we continue to see varying reported efficacy levels. While these numbers are significant, and have been very good, it is important to keep in mind what we are seeking. COVID-19 has resulted in mass hospitalization and death throughout the world, overwhelming hospitals in every country. However, a significant percentage of patients are not severely symptomatic. Unlike other diseases where mortality is high, this disease has a relatively low mortality, but its rapid spread throughout the world and high case numbers created a worldwide pandemic with massive casualties. The important vaccine efficacy statistic we are most concerned with is the reduction in hospitalization and death. The Moderna, Pfizer, and Johnson & Johnson vaccines showed complete protection against hospitalization and death after the full course of vaccination. That is an excellent result and one that should be stressed to all patients. Despite the varying “overall efficacy” percentages being published in the media, we seek to improve the overwhelming number of hospitalizations and death currently overrunning our hospitals. These vaccines have proven 100% effective in doing that, which is an incredible accomplishment.