Evidence map›Paper›PMID 35899968›Full record

ArticleTransplant infectious disease : an official journal of the Transplantation Society2022

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

Lacy M Simons, Egon A Ozer, Stephanie Gambut, Taylor J Dean, Li Zhang, Pavan Bhimalli, Jeffrey R Schneider, João I Mamede, Michael G Ison, Reem Karmali and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Transplant infectious disease : an official journal of the Transplantation Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.2field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Protracted SARS-CoV-2 Infection in B-cell Depleted Patients: Immunologic and Viral Characteristics and Response to Dual and Extended Antiviral Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  2. Review
  3. Quasi-species prevalence and clinical impact of evolving SARS-CoV-2 lineages in European COVID-19 cohorts, January 2020 to February 2022.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. SARS-CoV-2 genomics and impact on clinical care for COVID-19.The Journal of antimicrobial chemotherapy · 2023
    Article
  9. Article
  10. Observational
  11. Article
  12. De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.Transplant infectious disease : an official journal of the Transplantation Society · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Lacy M SimonsDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.ORCID https://orcid.org/0000-0003-4041-6775
Egon A OzerDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Stephanie GambutDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
Taylor J DeanDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Li ZhangDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
Pavan BhimalliDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
Jeffrey R SchneiderDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.ORCID https://orcid.org/0000-0001-9091-7653
João I MamedeDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
Michael G IsonDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.ORCID https://orcid.org/0000-0003-3347-9671
Reem KarmaliDepartment of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Leo I GordonDepartment of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Ramon Lorenzo-RedondoDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Judd F HultquistDepartment of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Northwestern University · USRush University Medical Center · US

Funding

Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
Technology CoreU19AI135964 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LUIS A. Nunes AMARAL · 2018 to 2026
$24.7M
Assessing the Risk of SARS-CoV-2 Remdesivir ResistanceR21AI163912 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HULTQUIST, JUDD F · 2021 to 2022
$440k
NCATS NIH HHS UL1 TR001422NIAID NIH HHS R21 AI163912NIAID NIH HHS U19 AI135964
6 · The paper itself

Abstract

backgroundThe 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.

methodsNasopharyngeal 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.

resultsOur 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.

conclusionsThese 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.

Indexed as

COVID-19SARS-CoV-2Antibodies, NeutralizingAntibodies, ViralAntiviral AgentsHumansImmunocompromised HostMutationAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsCOVID-19immunosuppressedpersistent infectionSARS-CoV-2spike mutationvariants of concernviral evolution

Identifiers

PMID35899968
PMCPMC9353292
OpenAlexW4288084883

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.