PMID- 34031661
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230818
DP  - 2022 Oct 12
TI  - A common allele of HLA mediates asymptomatic SARS-CoV-2 infection.
LID - 2021.05.13.21257065 [pii]
LID - 10.1101/2021.05.13.21257065 [doi]
AB  - 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.
FAU - Augusto, Danillo G
AU  - Augusto DG
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California San Francisco, San Francisco, CA, USA.
AD  - Programa de Pos-Graduacao em Genetica, Universidade Federal do Parana, Curitiba, 
      Brazil.
AD  - Department of Biological Sciences, The University of North Carolina at Charlotte, 
      Charlotte, NC, USA.
FAU - Yusufali, Tasneem
AU  - Yusufali T
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California San Francisco, San Francisco, CA, USA.
FAU - Sabatino, Joseph J Jr
AU  - Sabatino JJ Jr
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California San Francisco, San Francisco, CA, USA.
FAU - Peyser, Noah D
AU  - Peyser ND
AD  - Division of Cardiology, Department of Medicine, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Murdolo, Lawton D
AU  - Murdolo LD
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria 3086, Australia.
FAU - Butcher, Xochitl
AU  - Butcher X
AD  - Division of Cardiology, Department of Medicine, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Murray, Victoria
AU  - Murray V
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Pae, Vivian
AU  - Pae V
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Sarvadhavabhatla, Sannidhi
AU  - Sarvadhavabhatla S
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Beltran, Fiona
AU  - Beltran F
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Gill, Gurjot
AU  - Gill G
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Lynch, Kara
AU  - Lynch K
AD  - Department of Laboratory Medicine, University of California San Francisco, San 
      Francisco, CA, USA.
FAU - Yun, Cassandra
AU  - Yun C
AD  - Department of Laboratory Medicine, University of California San Francisco, San 
      Francisco, CA, USA.
FAU - Maguire, Colin
AU  - Maguire C
AD  - University of Utah, Clinical and Translational Science Institute, Salt Lake City, 
      UT.
FAU - Peluso, Michael J
AU  - Peluso MJ
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Hoh, Rebecca
AU  - Hoh R
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Henrich, Timothy J
AU  - Henrich TJ
AD  - Division of Experimental Medicine, Department of Medicine, University of 
      California San Francisco, San Francisco, CA, USA.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Davidson, Michelle
AU  - Davidson M
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Lu, Scott
AU  - Lu S
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Goldberg, Sarah A
AU  - Goldberg SA
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Kelly, J Daniel
AU  - Kelly JD
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
AD  - F.I. Proctor Foundation, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Martin, Jeffrey N
AU  - Martin JN
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Viera-Green, Cynthia A
AU  - Viera-Green CA
AD  - CIBMTR (Center for International Blood and Marrow Transplant Research), National 
      Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
FAU - Spellman, Stephen R
AU  - Spellman SR
AD  - CIBMTR (Center for International Blood and Marrow Transplant Research), National 
      Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
FAU - Langton, David J
AU  - Langton DJ
AD  - ExplantLab, The Biosphere, Newcastle Helix, Newcastle-upon-Tyne, UK.
FAU - Lee, Sulggi
AU  - Lee S
AD  - Division of HIV, Infectious Diseases, and Global Medicine, Department of 
      Medicine, University of California San Francisco, San Francisco, CA, USA.
FAU - Marcus, Gregory M
AU  - Marcus GM
AD  - Division of Cardiology, Department of Medicine, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Olgin, Jeffrey E
AU  - Olgin JE
AD  - Division of Cardiology, Department of Medicine, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Pletcher, Mark J
AU  - Pletcher MJ
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
AD  - Division of General Internal Medicine, University of California San Francisco, 
      San Francisco, CA, USA.
FAU - Gras, Stephanie
AU  - Gras S
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria 3086, Australia.
AD  - Department of Biochemistry and Molecular Biology, Biomedicine Discovery 
      Institute, Monash University, Clayton, Victoria 3800, Australia.
FAU - Maiers, Martin
AU  - Maiers M
AD  - National Marrow Donor Program, Minneapolis, MN.
FAU - Hollenbach, Jill A
AU  - Hollenbach JA
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California San Francisco, San Francisco, CA, USA.
AD  - Department of Epidemiology and Biostatistics, University of California San 
      Francisco, San Francisco, CA, USA.
LA  - eng
GR  - R01 AI159260/AI/NIAID NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
GR  - U2C EB021881/EB/NIBIB NIH HHS/United States
GR  - UL1 TR002538/TR/NCATS NIH HHS/United States
PT  - Preprint
DEP - 20221012
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - Nature. 2023 Jul 19;:. PMID: 37468623
PMC - PMC8142661
EDAT- 2021/05/26 06:00
MHDA- 2021/05/26 06:01
PMCR- 2022/12/14
CRDT- 2021/05/25 06:43
PHST- 2021/05/26 06:00 [pubmed]
PHST- 2021/05/26 06:01 [medline]
PHST- 2021/05/25 06:43 [entrez]
PHST- 2022/12/14 00:00 [pmc-release]
AID - 2021.05.13.21257065 [pii]
AID - 10.1101/2021.05.13.21257065 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2022 Oct 12:2021.05.13.21257065. doi: 
      10.1101/2021.05.13.21257065.