COVID-19 Update #65 for 1/26/2021

COVID-19 Vaccines
 
The CDC released some updates on COVID-19 vaccines.

• The agency continues to recommend the interval between doses, three weeks for the Pfizer-BioNTech vaccine and four weeks for Moderna’s vaccine, should be followed as closely as possible.
• If a patient is late for the second dose, they should receive the second vaccine by week six. There is not enough information to make a recommendation beyond six weeks, but an extra dose should not be administered if the second dose is not given by then. 
• The Pfizer-BioNTech and Moderna vaccines are not considered interchangeable.  However, if the initial vaccine a patient received cannot be determined or is not available, another mRNA vaccine may be given at least 28 days after the first vaccination. 
• Researchers estimate the incidence of anaphylaxis with the Pfizer-BioNTech COVID-19 vaccine as 11.1 cases per million doses administered. With Moderna’s vaccine, the CDC estimates the incidence of anaphylaxis to be 2.5 cases per million doses administered. 

Early data has become available describing the ability of the two approved mRNA vaccines for new SARS-CoV-2 mutations.

• In an unpublished and unedited report, researchers describe how antibodies in serum from 20 people, who had received two doses of the Pfizer-BioNTech COVID-19 vaccine, neutralized SARS-CoV-2 with and without the N501Y mutation with similar efficacy. The N501Y mutation has been identified as causing a faster spread of the disease in the U.K. It has also been identified in the U.S. N501Y is one of a series of mutations found in the B.1.1.7 lineage spike protein. In a second unpublished and unedited report, researchers describe how antibodies in serum from 16 people, who had received two doses of the Pfizer-BioNTech COVID-19 vaccine, neutralized SARS-CoV-2 pseudoviruses with the B.1.1.7 variant spike protein as well as it did the Wuhan reference strain.
• In an unpublished and unedited report, researchers describe how antibodies in serum from eight people, who had received two doses of Moderna’s COVID-19 vaccine, neutralized SARS-CoV-2 pseudoviruses with the B.1.1.7 variant as well as the Wuhan reference strain. But there was a reduction in antibody activity with the B.1.351 spike variant, however antibody activity was still adequate to fully neutralize the virus with the variant. Moderna is evaluating a second booster dose (three total doses) of its COVID-19 vaccine to boost antibody levels. The company is also developing a vaccine that elicits immunity to the variants. While with the B.1.1.7 variant has been identified in 50 countries and 20 U.S. states, the B.1.351 spike variant has been identified in South Africa.

Merck ceased development of two COVID-19 vaccines, when data from Phase I trials demonstrated the vaccines failed to elicit an immune response that was equivalent to recovered COVID-19 patients or other COVID-19 vaccines. Merck will focus research efforts on the development of an antiviral to treat COVID-19 and a recombinant fusion protein that modulates the inflammatory response. 

COVID-19 Antibodies
 
Lilly announced that in the 965 patient, Phase III, BLAZE-2 prevention trial (NCT04497987), fewer patients and staff that received bamlanivimab 4,200 mg developed COVID-19 than patients and staff who received placebo in 299 residents and 666 staff at skilled nursing and assisted living facilities. A pre-specified subgroup of residents had an 80% lower risk of testing positive for COVID-19 compared to residents in the same facility that received placebo. No deaths were reported in residents that received bamlanivimab compared to four that received placebo.
 
Final results from 577 patients enrolled in the 11-day, dose-ranging, Phase II portion of the BLAZE-1 trial (NCT04427501), that received bamlanivimab alone (700mg, 2,800mg or 7000mg) did not decrease viral load by day 11 compared to placebo in non-hospitalized patients with mild to moderate COVID-19. The full data set for the placebo groups was not available for the interim analysis, which may explain the difference in outcomes with the final analysis. However, the combination of bamlanivimab 2800 mg and etesevimab 2800 mg decreased the viral load compared to placebo. The combination group was also the only one that had a significant decrease in COVID-19 related hospitalizations or emergency department visits at day 29.
 
COVID-19 Anti-inflammatories
 
In the 15-day, 129 patient, Phase III, TOCIBRAS trial (NCT04403685), treatment with tocilizumab did not reduce a composite of death or mechanical ventilation (28% vs 20%) compared to placebo in patients with COVID-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). At 15-days, mortality was higher with tocilizumab compared to placebo (17% vs 3%), but the difference was no longer significant at day 29.