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Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19.
Fischer, Johannes C; Schmidt, Albrecht G; Bölke, Edwin; Uhrberg, Markus; Keitel, Verena; Feldt, Torsten; Jensen, Björn; Häussinger, Dieter; Adams, Ortwin; Schneider, E Marion; Balz, Vera; Enczmann, Jürgen; Rox, Jutta; Hermsen, Derik; Schulze-Bosse, Karin; Kindgen-Milles, Detlef; Knoefel, Wolfram Trudo; van Griensven, Martijn; Haussmann, Jan; Tamaskovics, Balint; Plettenberg, Christian; Scheckenbach, Kathrin; Corradini, Stefanie; Pedoto, Alessia; Maas, Kitti; Schmidt, Livia; Grebe, Olaf; Esposito, Irene; Ehrhardt, Anja; Peiper, Matthias; Buhren, Bettina Alexandra; Calles, Christian; Stöhr, Andreas; Lichtenberg, Artur; Freise, Noemi F; Lutterbeck, Matthias; Rezazadeh, Amir; Budach, Wilfried; Matuschek, Christiane.
  • Fischer JC; Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University, 40225, Dusseldorf, Germany.
  • Schmidt AG; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Bölke E; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany. boelke@med.uni-duesseldorf.de.
  • Uhrberg M; Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University, 40225, Dusseldorf, Germany.
  • Keitel V; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Feldt T; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Jensen B; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Häussinger D; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Adams O; Institute for Virology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Universitaetsstr. 1, 40225, Dusseldorf, Germany.
  • Schneider EM; Division of Experimental Anesthesiology, University Hospital Ulm, Ulm, Germany.
  • Balz V; Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University, 40225, Dusseldorf, Germany.
  • Enczmann J; Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University, 40225, Dusseldorf, Germany.
  • Rox J; Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University, 40225, Dusseldorf, Germany.
  • Hermsen D; Central Institute for Laboratory Diagnostics and Clinical Chemistry, Medical Faculty Heinrich-Heine University, Dusseldorf, Germany.
  • Schulze-Bosse K; Central Institute for Laboratory Diagnostics and Clinical Chemistry, Medical Faculty Heinrich-Heine University, Dusseldorf, Germany.
  • Kindgen-Milles D; Medical Faculty, Department of Anesthesiology, Heinrich Heine University, Dusseldorf, Germany.
  • Knoefel WT; Medical Faculty, Department of Surgery and Interdisciplinary Surgical Intensive Care Unit, Heinrich Heine University, Dusseldorf, Germany.
  • van Griensven M; Department cBITE, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht, the Netherlands.
  • Haussmann J; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Tamaskovics B; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Plettenberg C; Medical Faculty, Department of Ear, Nose and Throat Disease, Heinrich Heine University, Dusseldorf, Germany.
  • Scheckenbach K; Medical Faculty, Department of Ear, Nose and Throat Disease, Heinrich Heine University, Dusseldorf, Germany.
  • Corradini S; Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
  • Pedoto A; Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Maas K; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Schmidt L; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Grebe O; Department of Cardiology and Rhythmology, Petrus Hospital, Wuppertal, Germany.
  • Esposito I; Institute of Pathology, University of Dusseldorf, Dusseldorf, Germany.
  • Ehrhardt A; Institute of Virology, University of Witten/Herdecke, Witten, Germany.
  • Peiper M; Medical Faculty, University of Dusseldorf, Dusseldorf, Germany.
  • Buhren BA; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Calles C; Medical Faculty, Coordination Center for Clinical Studies, University of Dusseldorf, Dusseldorf, Germany.
  • Stöhr A; Medical Faculty, Coordination Center for Clinical Studies, University of Dusseldorf, Dusseldorf, Germany.
  • Lichtenberg A; Department of Cardiac Surgery, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany.
  • Freise NF; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Lutterbeck M; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Rezazadeh A; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Budach W; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
  • Matuschek C; Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
Eur J Med Res ; 26(1): 107, 2021 Sep 16.
Article in English | MEDLINE | ID: covidwho-1412355
ABSTRACT

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*0101 and HLA class I B*3501, with a trend for DRB1*0301). 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*0302 und HLA class I B*1501) 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*0101 and HLA class I B*3501 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.
Subject(s)
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Full text: Available Collection: International databases Database: MEDLINE Main subject: ABO Blood-Group System / Receptors, CCR5 / COVID-19 / HLA Antigens Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Eur J Med Res Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: S40001-021-00560-4

Full text: Available Collection: International databases Database: MEDLINE Main subject: ABO Blood-Group System / Receptors, CCR5 / COVID-19 / HLA Antigens Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Eur J Med Res Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: S40001-021-00560-4