Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
Authors
- J. Weiner
- P. Suwalski
- M. Holtgrewe
- A. Rakitko
- C. Thibeault
- M. Müller
- D. Patriki
- C. Quedenau
- U. Krüger
- V. Ilinsky
- I. Popov
- J. Balnis
- A. Jaitovich
- E.T. Helbig
- L.J. Lippert
- P. Stubbemann
- L.M. Real
- J. Macías
- J.A. Pineda
- M. Fernandez-Fuertes
- X. Wang
- Z. Karadeniz
- J. Saccomanno
- J.M. Doehn
- R.H. Hübner
- B. Hinzmann
- M. Salvo
- A. Blueher
- S. Siemann
- S. Jurisic
- J.H. Beer
- J. Rutishauser
- B. Wiggli
- H. Schmid
- K. Danninger
- R. Binder
- V.M. Corman
- B. Mühlemann
- R. Arjun Arkal
- G.K. Fragiadakis
- E. Mick
- C.S. Calfee
- D.J. Erle
- C.M. Hendrickson
- K.N. Kangelaris
- M.F. Krummel
- P.G. Woodruff
- C.R. Langelier
- U. Venkataramani
- F. García
- J. Zyla
- C. Drosten
- A. Braun
- T.C. Jones
- N. Suttorp
- M. Witzenrath
- S. Hippenstiel
- T. Zemojtel
- C. Skurk
- P. Wolfgang
- T. Borodina
- S. Ripke
- L.E. Sander
- D. Beule
- U. Landmesser
- T. Guettouche
- F. Kurth
- B. Heidecker
Journal
- EClinicalMedicine
Citation
- EClinicalMedicine 40: 101099
Abstract
BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ((n) = 135), Spain ((n) = 133), Switzerland ((n) = 20) and the United States ((n) = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted (p)-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2.