Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Julie Boucau; Kara W Chew; Manish C Choudhary; Rinki Deo; James Regan; James P Flynn; Charles R Crain; Michael D Hughes; Justin Ritz; Carlee Moser; Joan A Dragavon; Arzhang C Javan; Ajay Nirula; Paul Klekotka; Alexander L Greninger; Robert W Coombs; William A Fischer 2nd; Eric S Daar; David A Wohl; Joseph J Eron; Judith S Currier; Davey M Smith; POSITIVES study team; Jonathan Z Li; Amy K Barczak; ACTIV-2/A5401 Study Team

doi:10.1016/j.xcrm.2022.100678

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Cell Rep Med. 2022 Jul 19;3(7):100678. doi: 10.1016/j.xcrm.2022.100678. Epub 2022 Jun 20.

Authors

Julie Boucau¹, Kara W Chew², Manish C Choudhary³, Rinki Deo³, James Regan³, James P Flynn³, Charles R Crain³, Michael D Hughes⁴, Justin Ritz⁴, Carlee Moser⁴, Joan A Dragavon⁵, Arzhang C Javan⁶, Ajay Nirula⁷, Paul Klekotka⁷, Alexander L Greninger⁵, Robert W Coombs⁵, William A Fischer 2nd⁸, Eric S Daar⁹, David A Wohl⁸, Joseph J Eron⁸, Judith S Currier², Davey M Smith¹⁰; POSITIVES study team¹¹; Jonathan Z Li¹², Amy K Barczak¹³; ACTIV-2/A5401 Study Team

Affiliations

¹ The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
² Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁶ National Institutes of Health, Bethesda, MD, USA.
⁷ Lilly Research Laboratories, Eli Lilly and Company, San Diego, CA, USA.
⁸ Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
⁹ Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁰ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹¹ Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jli@bwh.harvard.edu.
¹³ The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: abarczak@mgh.harvard.edu.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission.

Keywords: COVID; COVID therapies; COVID-19; SARS-CoV-2; mAbs; monoclonal antibodies; resistance; viral culture.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Antibodies, Neutralizing
COVID-19 Drug Treatment*
Humans
SARS-CoV-2

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

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