tetano
Editor, Senior Moderator
EClinicalMedicine
. 2021 Sep 2;101099.
doi: 10.1016/j.eclinm.2021.101099. Online ahead of print.
Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
January Weiner[SUP] 1 [/SUP], Phillip Suwalski[SUP] 2 3 [/SUP], Manuel Holtgrewe[SUP] 4 [/SUP], Alexander Rakitko[SUP] 5 [/SUP], Charlotte Thibeault[SUP] 6 [/SUP], Melina Müller[SUP] 2 [/SUP], Dimitri Patriki[SUP] 7 [/SUP], Claudia Quedenau[SUP] 8 [/SUP], Ulrike Krüger[SUP] 4 [/SUP], Valery Ilinsky[SUP] 5 [/SUP], Iaroslav Popov[SUP] 5 [/SUP], Joseph Balnis[SUP] 9 [/SUP], Ariel Jaitovich[SUP] 9 [/SUP], Elisa T Helbig[SUP] 6 [/SUP], Lena J Lippert[SUP] 6 [/SUP], Paula Stubbemann[SUP] 6 [/SUP], Luis M Real[SUP] 10 [/SUP], Juan Macías[SUP] 10 [/SUP], Juan A Pineda[SUP] 10 [/SUP], Marta Fernandez-Fuertes[SUP] 10 [/SUP], Xiaomin Wang[SUP] 2 [/SUP], Zehra Karadeniz[SUP] 2 [/SUP], Jacopo Saccomanno[SUP] 6 [/SUP], Jan-Moritz Doehn[SUP] 6 [/SUP], Ralf-Harto Hübner[SUP] 6 [/SUP], Bernd Hinzmann[SUP] 11 [/SUP], Mauricio Salvo[SUP] 11 [/SUP], Anja Blueher[SUP] 11 [/SUP], Sandra Siemann[SUP] 11 [/SUP], Stjepan Jurisic[SUP] 7 [/SUP], Juerg H Beer[SUP] 7 [/SUP], Jonas Rutishauser[SUP] 7 [/SUP], Benedikt Wiggli[SUP] 7 [/SUP], Hansruedi Schmid[SUP] 7 [/SUP], Kathrin Danninger[SUP] 12 [/SUP], Ronald Binder[SUP] 12 [/SUP], Victor M Corman[SUP] 13 [/SUP], Barbara Mühlemann[SUP] 13 [/SUP], Rao Arjun Arkal[SUP] 14 15 16 [/SUP], Gabriela K Fragiadakis[SUP] 14 15 17 [/SUP], Eran Mick[SUP] 18 19 20 [/SUP], Consortium Comet[SUP] 21 [/SUP], Carolyn S Calfee[SUP] 18 [/SUP], David J Erle[SUP] 14 15 22 18 21 23 24 [/SUP], Carolyn M Hendrickson[SUP] 18 [/SUP], Kirsten N Kangelaris[SUP] 24 [/SUP], Matthew F Krummel[SUP] 14 16 [/SUP], Prescott G Woodruff[SUP] 14 18 16 25 [/SUP], Charles R Langelier[SUP] 19 20 [/SUP], Urmila Venkataramani[SUP] 14 15 [/SUP], Federico García[SUP] 26 [/SUP], Joanna Zyla[SUP] 27 [/SUP], Christian Drosten[SUP] 13 [/SUP], Braun Alice[SUP] 28 [/SUP], Terry C Jones[SUP] 13 29 30 [/SUP], Norbert Suttorp[SUP] 6 [/SUP], Martin Witzenrath[SUP] 6 [/SUP], Stefan Hippenstiel[SUP] 6 [/SUP], Tomasz Zemojtel[SUP] 4 [/SUP], Carsten Skurk[SUP] 2 [/SUP], Poller Wolfgang[SUP] 2 [/SUP], Tatiana Borodina[SUP] 8 [/SUP], Study Group Pa-Covid[SUP] 31 [/SUP], Stephan Ripke[SUP] 28 32 33 [/SUP], Leif E Sander[SUP] 6 [/SUP], Dieter Beule[SUP] 1 [/SUP], Ulf Landmesser[SUP] 2 34 [/SUP], Toumy Guettouche[SUP] 11 [/SUP], Florian Kurth[SUP] 6 [/SUP], Bettina Heidecker[SUP] 2 [/SUP]
Affiliations
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.
. 2021 Sep 2;101099.
doi: 10.1016/j.eclinm.2021.101099. Online ahead of print.
Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
January Weiner[SUP] 1 [/SUP], Phillip Suwalski[SUP] 2 3 [/SUP], Manuel Holtgrewe[SUP] 4 [/SUP], Alexander Rakitko[SUP] 5 [/SUP], Charlotte Thibeault[SUP] 6 [/SUP], Melina Müller[SUP] 2 [/SUP], Dimitri Patriki[SUP] 7 [/SUP], Claudia Quedenau[SUP] 8 [/SUP], Ulrike Krüger[SUP] 4 [/SUP], Valery Ilinsky[SUP] 5 [/SUP], Iaroslav Popov[SUP] 5 [/SUP], Joseph Balnis[SUP] 9 [/SUP], Ariel Jaitovich[SUP] 9 [/SUP], Elisa T Helbig[SUP] 6 [/SUP], Lena J Lippert[SUP] 6 [/SUP], Paula Stubbemann[SUP] 6 [/SUP], Luis M Real[SUP] 10 [/SUP], Juan Macías[SUP] 10 [/SUP], Juan A Pineda[SUP] 10 [/SUP], Marta Fernandez-Fuertes[SUP] 10 [/SUP], Xiaomin Wang[SUP] 2 [/SUP], Zehra Karadeniz[SUP] 2 [/SUP], Jacopo Saccomanno[SUP] 6 [/SUP], Jan-Moritz Doehn[SUP] 6 [/SUP], Ralf-Harto Hübner[SUP] 6 [/SUP], Bernd Hinzmann[SUP] 11 [/SUP], Mauricio Salvo[SUP] 11 [/SUP], Anja Blueher[SUP] 11 [/SUP], Sandra Siemann[SUP] 11 [/SUP], Stjepan Jurisic[SUP] 7 [/SUP], Juerg H Beer[SUP] 7 [/SUP], Jonas Rutishauser[SUP] 7 [/SUP], Benedikt Wiggli[SUP] 7 [/SUP], Hansruedi Schmid[SUP] 7 [/SUP], Kathrin Danninger[SUP] 12 [/SUP], Ronald Binder[SUP] 12 [/SUP], Victor M Corman[SUP] 13 [/SUP], Barbara Mühlemann[SUP] 13 [/SUP], Rao Arjun Arkal[SUP] 14 15 16 [/SUP], Gabriela K Fragiadakis[SUP] 14 15 17 [/SUP], Eran Mick[SUP] 18 19 20 [/SUP], Consortium Comet[SUP] 21 [/SUP], Carolyn S Calfee[SUP] 18 [/SUP], David J Erle[SUP] 14 15 22 18 21 23 24 [/SUP], Carolyn M Hendrickson[SUP] 18 [/SUP], Kirsten N Kangelaris[SUP] 24 [/SUP], Matthew F Krummel[SUP] 14 16 [/SUP], Prescott G Woodruff[SUP] 14 18 16 25 [/SUP], Charles R Langelier[SUP] 19 20 [/SUP], Urmila Venkataramani[SUP] 14 15 [/SUP], Federico García[SUP] 26 [/SUP], Joanna Zyla[SUP] 27 [/SUP], Christian Drosten[SUP] 13 [/SUP], Braun Alice[SUP] 28 [/SUP], Terry C Jones[SUP] 13 29 30 [/SUP], Norbert Suttorp[SUP] 6 [/SUP], Martin Witzenrath[SUP] 6 [/SUP], Stefan Hippenstiel[SUP] 6 [/SUP], Tomasz Zemojtel[SUP] 4 [/SUP], Carsten Skurk[SUP] 2 [/SUP], Poller Wolfgang[SUP] 2 [/SUP], Tatiana Borodina[SUP] 8 [/SUP], Study Group Pa-Covid[SUP] 31 [/SUP], Stephan Ripke[SUP] 28 32 33 [/SUP], Leif E Sander[SUP] 6 [/SUP], Dieter Beule[SUP] 1 [/SUP], Ulf Landmesser[SUP] 2 34 [/SUP], Toumy Guettouche[SUP] 11 [/SUP], Florian Kurth[SUP] 6 [/SUP], Bettina Heidecker[SUP] 2 [/SUP]
Affiliations
- PMID: 34490415
- PMCID: PMC8410317
- DOI: 10.1016/j.eclinm.2021.101099
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.