Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual

Peter J Halfmann; Nicholas R Minor; Luis A Haddock Iii; Robert Maddox; Gage K Moreno; Katarina M Braun; David A Baker; Kasen K Riemersa; Ankur Prasad; Kirsten J Alman; Matthew C Lambert; Kelsey Florek; Allen Bateman; Ryan Westergaard; Nasia Safdar; David R Andes; Yoshihiro Kawaoka; Madiha Fida; Joseph D Yao; Thomas C Friedrich; David H O'Connor

doi:10.1093/ve/veac104

Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual

Virus Evol. 2022 Nov 5;9(2):veac104. doi: 10.1093/ve/veac104. eCollection 2023.

Authors

Peter J Halfmann¹, Nicholas R Minor², Luis A Haddock Iii¹, Robert Maddox², Gage K Moreno², Katarina M Braun¹, David A Baker², Kasen K Riemersa¹, Ankur Prasad³, Kirsten J Alman⁴, Matthew C Lambert⁴, Kelsey Florek⁵, Allen Bateman⁵, Ryan Westergaard⁶, Nasia Safdar⁶, David R Andes⁶, Yoshihiro Kawaoka¹, Madiha Fida⁷, Joseph D Yao⁸, Thomas C Friedrich¹, David H O'Connor²

Affiliations

¹ Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Dr, Madison, WI 53706, USA.
² Department of Pathology and Laboratory Medicine, 3170 UW Medical Foundation Centennial Building (MFCB), 1685 Highland Avenue, Madison, WI 53705, USA.
³ Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI 53705-2281, USA.
⁴ University of Wisconsin Division of Infectious Disease, Room 5275-07C, 1685 Highland Avenue, Madison, WI 53705, USA.
⁵ Wisconsin State Laboratory of Hygiene, 2601 Agriculture Drive, PO Box 7996, Madison, WI 53707, USA.
⁶ Department of Medicine, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI 53705, USA.
⁷ Division of Infectious Diseases, Mayo Clinic, 200 First St. SW, Rochester, Rochester, Minnesota 55905, USA.
⁸ Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

Abstract

Prolonged infections in immunocompromised individuals may be a source for novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, particularly when both the immune system and antiviral therapy fail to clear the infection and enable within-host evolution. Here we describe a 486-day case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual's virus acquired resistance, likely via the earliest known occurrence of Spike amino acid variant E484T. Recently, E484T has arisen again as a derivative of E484A in the Omicron Variant of Concern, supporting the hypothesis that prolonged infections can give rise to novel variants long before they become prevalent in the human population.

Keywords: SARS-CoV-2; Spike protein; antibody escape; immunocompromised host; novel mutation; prolonged infection.

Abstract

Grants and funding