Your browser doesn't support javascript.
De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.
Simons, Lacy M; Ozer, Egon A; Gambut, Stephanie; Dean, Taylor J; Zhang, Li; Bhimalli, Pavan; Schneider, Jeffrey R; Mamede, João I; Ison, Michael G; Karmali, Reem; Gordon, Leo I; Lorenzo-Redondo, Ramon; Hultquist, Judd F.
  • Simons LM; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Ozer EA; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA.
  • Gambut S; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Dean TJ; 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 Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Schneider JR; Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA.
  • Mamede JI; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
  • Ison MG; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
  • Karmali R; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
  • Gordon LI; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
  • Lorenzo-Redondo R; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Hultquist JF; Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Transpl Infect Dis ; : e13914, 2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1961997
ABSTRACT

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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Topics: Variants Language: English Journal: Transpl Infect Dis Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Tid.13914

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Topics: Variants Language: English Journal: Transpl Infect Dis Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Tid.13914