De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.

Autor: Simons LM; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA., Ozer EA; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA., Gambut S; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA., Dean TJ; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA., Zhang L; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA., Bhimalli P; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA., Schneider JR; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA., Mamede JI; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA., Ison MG; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Karmali R; Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA., Gordon LI; Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Lorenzo-Redondo R; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA., Hultquist JF; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: Transplant infectious disease : an official journal of the Transplantation Society [Transpl Infect Dis] 2022 Dec; Vol. 24 (6), pp. e13914. Date of Electronic Publication: 2022 Aug 01.
DOI: 10.1111/tid.13914
Abstrakt: Background: The continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts.
Methods: Nasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro.
Results: Our sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry.
Conclusions: These observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.
(© 2022 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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