Bamlanivimab reduces nasal viral levels and inflammation but not symptom duration when given for early COVID-19 treatment

Bamlanivimab, which received the first US Food and Drug Administration (FDA) Emergency Use Authorization for outpatient treatment of COVID-19, was the first investigational drug to be studied in the ACTIV-2 platform trial. The bamlanivimab study within ACTIV-2 was designed to determine whether bamlanivimab reduced virus detection on deep swabs of the nose and shortened the time it took for COVID-19 symptoms to improve, compared to placebo.

Researchers found that while bamlanivimab did not reduce how long it took for symptoms to improve or the number of participants with undetectable nasal viral levels compared to placebo, it did lead to faster reductions in the amount of detectable virus compared to no treatment. Markers of inflammation in the blood (C-reactive protein [CRP], ferritin, and fibrinogen) also decreased more quickly with bamlanivimab compared to placebo, with the effects on CRP lasting through 24 weeks after treatment.

This study provides insights on how bamlanivimab treatment might have helped prevent hospitalizations and deaths as was reported in other clinical trials. The study also shed light on how the way we measure antiviral activity in trials can make a big difference in knowing if a COVID-19 treatment works or not to reduce virus – we found that modeling viral decay rates may show the activity of a COVID-19 antiviral treatment more reliably than looking only at how much virus is present at different time points.

Note: Although bamlanivimab is no longer used because of limited activity against SARS-CoV-2 variants (e.g., Omicron), these types of studies help us understand what monoclonal antibodies can and cannot do and are important for future studies of antiviral monoclonal antibodies for viral respiratory diseases.

Kara W Chew, Carlee Moser, Eric S Daar, David A Wohl, Jonathan Z Li, Robert W Coombs, Justin Ritz, Mark Giganti, Arzhang Cyrus Javan, Yijia Li, Manish C Choudhary, Rinki Deo, Carlos Malvestutto, Paul Klekotka, Karen Price, Ajay Nirula, William Fischer, Veenu Bala, Ruy M Ribeiro, Alan S Perelson, Courtney V Fletcher, Joseph J Eron, Judith S Currier, ACTIV-2/A5401 Study Team; Michael D Hughes, Davey M Smith. Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19. Nat Commun. 2022 Aug 22;13(1):4931. doi: 10.1038/s41467-022-32551-2.