Evidence map›Paper›PMID 40402577›Full record

ArticleJCI insight2025

High-affinity CD16A polymorphism associated with reduced risk ofsevere COVID-19.

Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery and 46 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

56 authors.

Anita E QuallsDepartment of Microbiology and Immunology, UCSF, San Francisco, California, USA.
Tasha TsaoDepartment of Microbiology and Immunology, UCSF, San Francisco, California, USA.
Irene LuiDepartment of Pharmaceutical Chemistry, Department of Cellular and Molecular Pharmacology, and Chan Zuckerberg Biohub, UCSF, San Francisco, California, USA.
Shion A LimDepartment of Pharmaceutical Chemistry, Department of Cellular and Molecular Pharmacology, and Chan Zuckerberg Biohub, UCSF, San Francisco, California, USA.
Yapeng SuInstitute for Systems Biology, Seattle, Washington, USA.
Ernie ChenYale School of Medicine, New Haven, Connecticut, USA.
Dylan DuchenYale School of Medicine, New Haven, Connecticut, USA.
Holden T MaeckerStanford University School of Medicine, Palo Alto, California, USA.
Seunghee Kim-SchulzeIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Ruth R MontgomeryYale School of Medicine, New Haven, Connecticut, USA.
Florian KrammerIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Charles R LangelierDepartment of Medicine, UCSF, San Francisco, California, USA.
Ofer LevyPrecision Vaccines Program, Boston Children's Hospital, and.
Lindsey R BadenBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Esther MelamedThe University of Texas at Austin, Austin, Texas, USA.
Lauren Ir EhrlichThe University of Texas at Austin, Austin, Texas, USA.
Grace A McComseyCase Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
Rafick P SekalyCase Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
Charles B CairnsDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Elias K HaddadDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Albert C ShawYale School of Medicine, New Haven, Connecticut, USA.
David A HaflerYale School of Medicine, New Haven, Connecticut, USA.
David B CorryBaylor College of Medicine and the Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
Farrah KheradmandBaylor College of Medicine and the Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
Mark A AtkinsonUniversity of Florida, Gainesville, Florida, USA.
Scott C BrakenridgeUniversity of Florida, Gainesville, Florida, USA.
Nelson I Agudelo HiguitaOklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Jordan P MetcalfOklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Catherine L HoughOregon Health & Science University, Portland, Oregon, USA.
William B MesserOregon Health & Science University, Portland, Oregon, USA.
Bali PulendranStanford University School of Medicine, Palo Alto, California, USA.
Kari C NadeauStanford University School of Medicine, Palo Alto, California, USA.
Mark M DavisStanford University School of Medicine, Palo Alto, California, USA.
Ana Fernandez-SesmaIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Viviana SimonIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Monica KraftUniversity of Arizona, Tucson, Arizona, USA.
Christian BimeUniversity of Arizona, Tucson, Arizona, USA.
Carolyn S CalfeeDepartment of Medicine, UCSF, San Francisco, California, USA.
David J ErleDepartment of Medicine, UCSF, San Francisco, California, USA.
Joanna SchaenmannDavid Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Al OzonoffClinical and Data Coordinating Center (CDCC), Boston Children's Hospital, Boston, Massachusetts, USA.
Bjoern PetersLa Jolla Institute for Immunology, La Jolla, California, USA.
Steven H KleinsteinYale School of Medicine, New Haven, Connecticut, USA.
Alison D AugustineNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Joann Diray-ArceClinical and Data Coordinating Center (CDCC), Boston Children's Hospital, Boston, Massachusetts, USA.
Patrice M BeckerNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Nadine RouphaelEmory School of Medicine, Atlanta, Georgia, USA.
IMPACC Network
Jason D GoldmanSwedish Center for Research and Innovation, Providence Swedish Medical Center, Seattle, Washington, USA.
Daniel R CalabreseDepartment of Medicine, UCSF, San Francisco, California, USA.
James R HeathInstitute for Systems Biology, Seattle, Washington, USA.
James A WellsDepartment of Pharmaceutical Chemistry, Department of Cellular and Molecular Pharmacology, and Chan Zuckerberg Biohub, UCSF, San Francisco, California, USA.
Elaine F ReedDavid Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Lewis L LanierDepartment of Microbiology and Immunology, UCSF, San Francisco, California, USA.
Harry PickeringDavid Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Oscar A AguilarDepartment of Microbiology and Immunology, UCSF, San Francisco, California, USA.

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Translation of immunologic technologies from basic research into pre-clinical nonU19AI062629 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI COGGESHALL, KENNETH MARK · 2004 to 2023
$56.2M
Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Albert C Shaw · 2010 to 2026
$50.4M
Project 3 - Ex vivo immune profiling of dengue viruses and vaccinesU19AI118610 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HARRIS, EVA · 2015 to 2021
$46.6M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRESCOTT G WOODRUFF · 2008 to 2026
$41.1M
Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
Tollip inhibits IL-33 signaling during airway influenza virus infectionU19AI125357 · NIAID · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA, VERCELLI, DONATA · 2016 to 2025
$14.7M
Systems biological assessment of T cell responses to vaccinationU19AI167903 · NIAID · STANFORD UNIVERSITY · PI BALI PULENDRAN · 2022 to 2026
$13.2M
Project 3: Mapping the Evolution of Chronic Transplant Injury in the Context of CMV InfectionU19AI128913 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F, SARWAL, MINNIE M · 2017 to 2021
$11.2M
Medical Scientist Training Program (T32 NRSA Training Grant)T32GM141323 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aimee Kao · 2021 to 2026
$10.5M
BLRD VA I01 BX005023NIAID NIH HHS N01 AI025482NIAID NIH HHS N01 AI025496NIAID NIH HHS R01 AI104870NIAID NIH HHS R01 AI122220NIAID NIH HHS R01 AI135803NIAID NIH HHS R01 AI145835NIAID NIH HHS R01 AI146581NIAID NIH HHS R56 AI146581NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI062629NIAID NIH HHS U19 AI077439NIAID NIH HHS U19 AI089992NIAID NIH HHS U19 AI090023NIAID NIH HHS U19 AI118608NIAID NIH HHS U19 AI118610NIAID NIH HHS U19 AI125357NIAID NIH HHS U19 AI128910NIAID NIH HHS U19 AI128913NIAID NIH HHS U19 AI167903NIAID NIH HHS U54 AI142766NIDA NIH HHS T32 DA018926NIDDK NIH HHS P30 DK063720NIGMS NIH HHS T32 GM136547NIGMS NIH HHS T32 GM141323NIH HHS S10 OD026940
6 · The paper itself

Abstract

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 cohort (IMPACC), a comprehensive longitudinal dataset with extensive transcriptomic, proteomic, and clinical data. The high-affinity CD16AV176 allele was associated with a significantly reduced risk of ICU admission, mechanical ventilation, and severe disease trajectories. Lower anti-SARS-CoV-2 IgG titers were correlated to CD16AV176; however, there was no difference in viral load across CD16A genotypes. Proteomic analysis revealed that participants homozygous for CD16AV176 had lower levels of inflammatory mediators. These findings suggest that CD16AV176 enhances early NK cell-mediated immune responses, limiting severe respiratory complications in COVID-19. This study identifies a protective genetic factor against severe COVID-19, informing future host-directed therapeutic strategies.

Indexed as

COVID-19Receptors, IgGAdultAgedAllelesAntibody-Dependent Cell CytotoxicityFemaleGenetic Predisposition to DiseaseHumansKiller Cells, NaturalMaleMiddle AgedPolymorphism, GeneticSARS-CoV-2Severity of Illness IndexViral LoadFCGR3A protein, humanReceptors, IgGCellular immune responseCOVID-19ImmunologyInnate immunityNK cells

Identifiers

PMID40402577
PMCPMC12306582

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.