By Daniel R. Lucey MD, MPH, FIDSA
The United States Centers for Disease Control and Prevention this month has provided helpful updates on its website focusing on SARS-CoV-2 variants and their prevalence state-by-state. This information helps clinicians understand where variants are as well as make decisions on use of monoclonal antibodies that have U.S. Food and Drug Administration authorization for outpatient therapy. When specific variants are known to be resistant to specific individual monoclonal antibodies, then combination “cocktails” of monoclonals could still be effective. For example, on March 10 the Department of Health and Human Services issued a statement that:
“The USG is evaluating recommendations for use of bamlanivimab in regions where the SARS-CoV2 mutation L452R found in B.1.429/B.1.427 lineages (a.k.a. 20C/CAL.20C) is circulating in high numbers given concerns that the clinical activity of bamlanivimab is impacted by this variant. ASPR will limit distribution to these regions of the country by stopping direct ordering for bamlanivimab while evaluations are ongoing.
Currently, this action will only affect the states of California, Arizona, and Nevada. The other two authorized products, bamlanivimab/etesevimab and casirivimab/imdevimab, do not appear to be affected and will continue to be available for direct ordering in these states.”
The CDC website on variants, updated March 16, stated that the variants first found in California (B.1. 427/B.1.429) contains a key mutation “L452R” in the receptor binding domain and has “~ 20% increased transmissibility, significant impact on neutralization by some, but not all, EUA therapeutics, and moderate reduction in neutralization using convalescent and post-vaccination sera.”
On another CDC webpage Variant Proportions in the U.S. | CDC titled: “Variant Proportions in the U.S.”, the following “proportions of SARS-CoV-2 Variants of Concern by State” list California as having 52% B.1.427/B.1.429, Nevada having 41%, and Arizona 25% B.1.1.427/B.1.429. Notably, these percentages could be higher now (March 23), given that CDC stated they are based on four-week data ending February 23.
We can anticipate that similar limits on specific monoclonal antibodies may occur as this variant B.1.427/B.1.429 spreads to more locations in the U.S..
In addition, in the USA variants containing the E484K mutations e.g., the B.1.351, the P.1, and some of the B.1.526 that are associated with resistance to some specific monoclonal antibodies would warrant similar restrictions if they become more widespread in some states and maybe even some large cities. ( March 4 Nature and March 8 Nature.)
Daniel Lucey, M.D. MPH, FIDSA, FACP, is a Clinical Professor of Medicine at Dartmouth Geisel School of Medicine, Infectious Disease adjunct Professor at Georgetown Medical Center, senior scholar at Georgetown Law, Anthropology Research Associate at the Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee. He served as a volunteer to outbreaks overseas including hands-on Ebola patient care in Sierra Leone and Liberia (Doctors without Borders) 2014, MERS 2013, SARS 2003, as well as HIV, H5N1, Zika, yellow Fever, and pneumonic plague 2017 (with WHO/USAID/CDC). Since Jan. 6, 2020 he has contributed over 75 posts to Science Speaks on COVID-19 and traveled to China in February 2020. He initially proposed, then fundraised and helped design the content for 2018-2022 Smithsonian Exhibition on Epidemics due to zoonotic viruses. From 1982-1988 he trained at University of California San Francisco and Harvard and was an attending physician at the NIH (NIAID) in the 1990s while in the US Public Health Service.