SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape

Camille Wouters, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Jaiprasath Sachithanandham, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Elgin Akin, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Lisa Pieterse, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Amary Fall, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Thao T. Truong, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
Jennifer Dien Bard, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Rebecca Yee, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
David J. Sullivan, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Heba H. Mostafa, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Andrew Pekosz, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

Document Type

Journal Article

Publication Date

9-9-2024

Journal

Viruses

Volume

16

Issue

9

DOI

10.3390/v16091436

Keywords

SARS-CoV-2; immunocompromised host; neutralizing antibody escape; syncytia; virus evolution

Abstract

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient-who did mount a SARS-CoV-2 IgM response-showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.

Department

Pathology

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