Evidence map›Paper›PMID 41170974›Full record

ArticleJournal of virology2025

Tissue tropism and functional adaptation of the SARS-CoV-2 spike protein in a fatal case of COVID-19.

Katherine E E Johnson, Sydney Stein, Rita Afriyie Boateng, Shilpi Jain, Sabrina C Ramelli, Trevor Stantliff, Shelly Curran, Marcos J Ramos-Benítez, Andrew P Platt, Stephanie Banakis and 13 more

Abstract readCase Reports
In one paragraph

Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Katherine E E JohnsonSystems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Sydney SteinCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Rita Afriyie BoatengSystems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Shilpi JainDivision of Infectious Diseases, Department of Pediatrics, Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
Sabrina C RamelliCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Trevor StantliffCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Shelly CurranCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Marcos J Ramos-BenítezCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Andrew P PlattCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Stephanie BanakisSystems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Wei WangSystems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Stephen M HewittLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Christa ZerbeDivision of Intramural Research, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0003-4219-0503
Steven M HollandDivision of Intramural Research, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Elizabeth M KangDivision of Intramural Research, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Manmeet SinghLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Emmie de WitLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
William A LauerDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, USA.
Eric C RouchkaDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, USA.
Melissa SmithDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, USA.
Mehul S SutharDivision of Infectious Diseases, Department of Pediatrics, Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
Daniel S ChertowCritical Care Medicine Department, Emerging Pathogens Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Elodie GhedinSystems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0002-1515-725X

Funding

WKU Lead Faculty AwardP20GM103436 · NIGMS · UNIVERSITY OF LOUISVILLE · PI Bruce A Mattingly · 2012 to 2026
$60.1M
NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00017 · NIAID · EMORY UNIVERSITY · PI LOWEN, ANICE · 2021 to 2025
$27.3M
The role of ECM-mediated mechanosignaling on regional immunosuppression in GBMP20GM135004 · NIGMS · UNIVERSITY OF LOUISVILLE · PI JUN YAN · 2020 to 2026
$21.1M
NIAID NIH HHS 75N93021C00017NIGMS NIH HHS P20 GM103436NIGMS NIH HHS P20 GM135004
6 · The paper itself

Abstract

Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites. Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission. In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency. We identified tissue-specific virus genotypes, in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. This highlights the importance of studying patients with weakened immune responses where potential tissue reservoirs provide an environment permissive for SARS-CoV-2 evolution and diversification.IMPORTANCEPersistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals are considered a potential source of new viral variants. Beyond the respiratory tract, the virus can spread within days to organs like the brain, heart, and kidneys, where distinct tissue microenvironments may further drive viral evolution and the emergence of new mutations. In this study, we compared the genetic diversity of SARS-CoV-2 genomic RNA isolated from 27 distinct tissue sites collected from an individual with a weakened immune system. By linking viral population dynamics across these tissue sites, we defined the extent of compartmentalization during multi-organ spread, highlighting how non-respiratory tissues can impact SARS-CoV-2 diversification.

Indexed as

COVID-19SARS-CoV-2Spike Glycoprotein, CoronavirusViral TropismFatal OutcomeGenome, ViralHumansMaleMutationSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2coronavirustissue tropismviral evolutionviral intrahost diversity

Identifiers

PMID41170974
PMCPMC12645954

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.