From the Curator-in-Chief's Desk—Dec. 3, 2021

Omicron Variant of Concern Found Globally

The WHO recently classified the SARS-CoV-2 B.1.1.529 lineage as the variant of concern Omicron, which has been identified in over 20 countries including the U.S. Omicron contains over 50 mutations, with the majority of changes in the gene encoding the spike protein. Some of these mutation have been associated with immune escape and increased transmissibility. In a preprint, Pulliam, J. et al. analyzed more than 35,000 samples from suspected reinfections, finding a higher risk of reinfection corresponding to the emergence of the Omicron variant. However, many questions remain about Omicron, and more time and cases will be needed to determine Omicron’s true impact on disease severity and transmission. Thankfully, surveillance by South African scientists alerted the global community so that we can plan and better prepare for this variant. Omicron’s emergence is a reminder for us to stay vigilant with public health measures, such as mask wearing, social distancing and hand washing, in combination with increasing vaccinations worldwide.

COVID-19 Vaccines and Boosters to Slow the Spread

The CDC recommended all U.S. adults 18 and older should receive a SARS-CoV-2 vaccine booster when eligible as an added layer of protection from emerging variants. To understand the science behind boosters, Drs. John Dennehy, Leo Poon, Linda Saif, Rachel Burckhardt and I wrote a commentary in Journal of Virology analyzing known data about vaccine safety, immunology and epidemiology. Boosters have been shown to be safe and increase SARS-CoV-2-specific neutralizing antibody levels that neutralize current variants. But vaccinating the same groups while large portions of the world remain unvaccinated will hinder our efforts for global herd immunity and perpetuate the emergence of variants. Only ~6% of people in low-income countries have received at least 1 dose of a vaccine compared to ~40% in high-income countries. Global vaccine equity must be a priority.

Development of Oral Antivirals for SARS-CoV-2

This week, the FDA advisory panel recommended authorizing molnupiravir developed by Merck and Ridgeback. If authorized, it would be the first oral SARS-CoV-2 antiviral in the U.S. and has been shown to reduce the risk of COVID-19 hospitalizations or deaths by 30%. Pfizer also developed an oral antiviral that Frederick G. Hayden, M.D., Professor Emeritus, Medicine: Infectious Diseases and International Health, University of Virginia, described in this week’s commentary on ASM Connect. In their Science paper “An oral SARS-CoV-2 M^pro inhibitor clinical candidate for the treatment of COVID-19,” Owen, D., et al. characterized the SARS-CoV-2 M^pro cysteine protease inhibitor PF-7321332, finding it inhibited SARS-CoV-2 replication in cell cultures and mouse models at nanomolar concentrations. Hayden highlights that the M^pro viral protein is conserved across coronaviruses, making PF-7321332 an attractive pan-coronavirus antiviral. Additionally, results from a placebo-controlled study of non-hospitalized COVID-19 patients found administration of PAXLOVID™, which is a combination of PF-7321332 and ritonavir, decreased the risk of hospitalization or death by 89%. Ullrich, S., et al. demonstrated that PF-7321332 remains potent against mutated M^pro from SARS-CoV-2 variants. Accessible at-home treatments will be important as COVID-19 cases continue to rise this winter.

Dec. 3, 2021

By Frederick G. Hayden, M.D., Stuart S Richardson Professor Emeritus of Clinical Virology and Professor Emeritus of Medicine in the Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Va. Hayden is a curator of the registry.

"An oral SARS-CoV-2 M^pro inhibitor clinical candidate for the treatment of COVID-19" by Owen, D., et al. published in Science on Nov. 2, 2021.
View the Commentary on ASM Connect View Past Commentaries