Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

  1. Fischer, Johannes C.
  2. Schmidt, Albrecht G.
  3. Boelke, Edwin ORCID logo
  4. Uhrberg, Markus
  5. Keitel, Verena
  6. Feldt, Torsten
  7. Jensen, Björn
  8. Häussinger, Dieter
  9. Adams, Ortwin
  10. Schneider, E. Marion
  11. Balz, Vera
  12. Enczmann, Jürgen
  13. Rox, Jutta
  14. Hermsen, Derik
  15. Schulze-Bosse, Karin
  16. Kindgen-Milles, Detlef
  17. Knoefel, Wolfram Trudo
  18. van Griensven, Martijn
  19. Haussmann, Jan
  20. Tamaskovics, Balint
  21. Plettenberg, Christian
  22. Scheckenbach, Kathrin
  23. Corradini, Stefanie
  24. Pedoto, Alessia
  25. Maas, Kitti
  26. Schmidt, Livia
  27. Grebe, Olaf
  28. Esposito, Irene
  29. Ehrhardt, Anja
  30. Peiper, Matthias
  31. Buhren, Bettina Alexandra
  32. Calles, Christian
  33. Stöhr, Andreas
  34. Lichtenberg, Artur
  35. Freise, Noemi F.
  36. Lutterbeck, Matthias
  37. Rezazadeh, Amir
  38. Budach, Wilfried
  39. Matuschek, Christiane

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1000 Titel
  • Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19
1000 Autor/in
  1. Fischer, Johannes C. |
  2. Schmidt, Albrecht G. |
  3. Boelke, Edwin |
  4. Uhrberg, Markus |
  5. Keitel, Verena |
  6. Feldt, Torsten |
  7. Jensen, Björn |
  8. Häussinger, Dieter |
  9. Adams, Ortwin |
  10. Schneider, E. Marion |
  11. Balz, Vera |
  12. Enczmann, Jürgen |
  13. Rox, Jutta |
  14. Hermsen, Derik |
  15. Schulze-Bosse, Karin |
  16. Kindgen-Milles, Detlef |
  17. Knoefel, Wolfram Trudo |
  18. van Griensven, Martijn |
  19. Haussmann, Jan |
  20. Tamaskovics, Balint |
  21. Plettenberg, Christian |
  22. Scheckenbach, Kathrin |
  23. Corradini, Stefanie |
  24. Pedoto, Alessia |
  25. Maas, Kitti |
  26. Schmidt, Livia |
  27. Grebe, Olaf |
  28. Esposito, Irene |
  29. Ehrhardt, Anja |
  30. Peiper, Matthias |
  31. Buhren, Bettina Alexandra |
  32. Calles, Christian |
  33. Stöhr, Andreas |
  34. Lichtenberg, Artur |
  35. Freise, Noemi F. |
  36. Lutterbeck, Matthias |
  37. Rezazadeh, Amir |
  38. Budach, Wilfried |
  39. Matuschek, Christiane |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-09-16
1000 Erschienen in
1000 Quellenangabe
  • 26(1):107
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s40001-021-00560-4 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444184/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5).!##!Patient and methods!#!An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation.!##!Results!#!Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing.!##!Conclusion!#!The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.
1000 Sacherschließung
gnd 1206347392 COVID-19
lokal Histocompatibility Antigens Class I/genetics [MeSH]
lokal Receptors, CCR5/genetics [MeSH]
lokal Aged [MeSH]
lokal HLA-DRB1 Chains/genetics [MeSH]
lokal HLA class I genotypes
lokal CCR5
lokal COVID-19/genetics [MeSH]
lokal COVID-19/etiology [MeSH]
lokal Male [MeSH]
lokal Neutralizing antibodies
lokal COVID-19/epidemiology [MeSH]
lokal Clinical course
lokal SARS-CoV-2
lokal Chemokine receptor
lokal Genetic Predisposition to Disease [MeSH]
lokal Female [MeSH]
lokal ABO Blood-Group System/genetics [MeSH]
lokal Mutation [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Severity of Illness Index [MeSH]
lokal HLA Antigens/genetics [MeSH]
lokal Middle Aged [MeSH]
lokal COVID-19
lokal ABO blood group
lokal Morbidity [MeSH]
lokal Research
lokal Genotype [MeSH]
lokal Immunoglobulin G/blood [MeSH]
1000 Liste der Beteiligten
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