Evidence map›Paper›PMID 34031661›Full record

ArticlemedRxiv : the preprint server for health sciences2022

A common allele of HLA mediates asymptomatic SARS-CoV-2 infection.

Danillo G Augusto, Tasneem Yusufali, Joseph J Sabatino, Noah D Peyser, Lawton D Murdolo, Xochitl Butcher, Victoria Murray, Vivian Pae, Sannidhi Sarvadhavabhatla, Fiona Beltran and 23 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2022. 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, 15 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 5 institutions in 3 countries.

Danillo G AugustoWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Tasneem YusufaliWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Joseph J SabatinoWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Noah D PeyserDivision of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lawton D MurdoloDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia.
Xochitl ButcherDivision of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Victoria MurrayDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Vivian PaeDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Sannidhi SarvadhavabhatlaDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Fiona BeltranDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Gurjot GillDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Kara LynchDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Cassandra YunDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Colin MaguireUniversity of Utah, Clinical and Translational Science Institute, Salt Lake City, UT.
Michael J PelusoDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Rebecca HohDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Timothy J HenrichDivision of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Steven G DeeksDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Michelle DavidsonDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Scott LuDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Sarah A GoldbergDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
J Daniel KellyDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Jeffrey N MartinDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Cynthia A Viera-GreenCIBMTR (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
Stephen R SpellmanCIBMTR (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
David J LangtonExplantLab, The Biosphere, Newcastle Helix, Newcastle-upon-Tyne, UK.
Sulggi LeeDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Gregory M MarcusDivision of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Jeffrey E OlginDivision of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Mark J PletcherDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Stephanie GrasDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia.
Martin MaiersNational Marrow Donor Program, Minneapolis, MN.
Jill A HollenbachWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
University of California, San Francisco · USNational Marrow Donor Program · USLa Trobe University · AUUniversity of North Carolina at Charlotte · USUniversity of Utah · US

Funding

Data Resource for Analyzing Blood &Marrow TransplantsU24CA076518 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Amy M Moskop, Bronwen Shaw · 1998 to 2026
$105.2M
Utah Center for Clinical and Translational ScienceUL1TR002538 · NCATS · UNIVERSITY OF UTAH · PI HESS, RACHEL, MAJERSIK, JENNIFER JUHL · 2018 to 2022
$26.0M
The Health ePeople Resource for Mobilized ResearchU2CEB021881 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARCUS, GREGORY M, OLGIN, JEFFREY E · 2015 to 2020
$10.3M
Training in HIV Translational ResearchT32AI060530 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Diane V Havlir · 2005 to 2026
$6.4M
Integrated Exchange and Storage of Current- and Future-Generation Immunogenomic DataR01AI128775 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JILL Allison HOLLENBACH, STEVEN JOHN MACK · 2017 to 2026
$4.5M
MHC Variation in Host Response to SARS-CoV2 and COVID-19 OutcomesR01AI159260 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOLLENBACH, JILL ALLISON · 2021 to 2025
$4.0M
NCATS NIH HHS UL1 TR002538NCI NIH HHS U24 CA076518NIAID NIH HHS R01 AI159260NIAID NIH HHS T32 AI060530NIBIB NIH HHS U2C EB021881
6 · The paper itself

Abstract

Despite some inconsistent reporting of symptoms, studies have demonstrated that at least 20% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will remain asymptomatic. Although most global efforts have focused on understanding factors underlying severe illness in COVID-19 (coronavirus disease of 2019), the examination of asymptomatic infection provides a unique opportunity to consider early disease and immunologic features promoting rapid viral clearance. Owing to its critical role in the immune response, we postulated that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in the UCSF Citizen Science smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n=1428) was comprised of unvaccinated, self-identified subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with disease course and identified a strong association of HLA-B*15:01 with asymptomatic infection, and reproduced this association in two independent cohorts. Suggesting that this genetic association is due to pre-existing T-cell immunity, we show that T cells from pre-pandemic individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF, and 100% of the reactive cells displayed memory phenotype. Finally, we characterize the protein structure of HLA-B*15:01-peptide complexes, demonstrating that the NQKLIANQF peptide from SARS-CoV-2, and the highly homologous NQKLIANAF from seasonal coronaviruses OC43-CoV and HKU1-CoV, share similar ability to be stabilized and presented by HLA-B*15:01, providing the molecular basis for T-cell cross-reactivity and HLA-B*15:01-mediated pre-existing immunity.

Identifiers

PMID34031661
PMCPMC8142661
OpenAlexW3161654498

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Registered trials

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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.