HLA and AB0 Polymorphisms Influence SARS CoV 2 Infection and COVID 19 Severity

Background: SARS-CoV-2 infection is heterogenous in clinical presentation and disease evolution. We investigated whether genetic variability can in of immune response to the virus can be influenced by genetic factors. Specifically, we compared HLA and AB0 frequencies in organ transplant recipients and in waitlisted patients according to the presence or absence of SARS-CoV-2 infection. Methods: A retrospective analysis was performed on an Italian cohort composed by subjects who received organ transplantation and candidates in waiting list in a January 2002-March 2020 time frame. Data from this cohort were merged with the Italian Ministry of Health registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (COVID+) or absence (COVID-) of SARS-CoV-2 infection. Findings: The cumulative incidence rate of COVID-19 was 0·112% in the Italian population and 0·462% in waitlisted/transplanted patients (OR=4·2, 95% CI [3·7-4·7], p<0·0001). HLA-B*51 was more frequent in COVID+ (25·1%) compared to COVID- (17·7%: OR=1·6, 95%CI [1·1-2·1]; p=0·004), as well as HLA-DRB1*08 (9·7% and 5·2%: OR=1·9, 95% CI [1·2-3·1]; p=0·003). Conversely, HLA-DRB1*07 showed a protective effect (15·2% in COVID+ vs. 21·6% in COVID-: OR=0·7, 95% CI [0·5-0·9]; p=0·023). In transplant recipients, HLA-DRB1*08 was correlated to mortality (1·9% in living vs 15·2% in deceased: OR=9·4 95% CI [1·9-47·3]; p=0.006). Lastly, blood group A was more frequent in COVID+ (45·5%) than in COVID- patients (39%; OR=1·3, 95% CI [1·0-1·7]; p=0·033). Interpretation: These results show that HLA antigens can influence SARS-CoV-2 infection and clinical evolution of COVID-19. They also confirm that blood group A subjects are at greater risk of infection. Overall, this study provides clues on the different spread of the disease and indications about infection prognosis and vaccination strategies. Funding Statement: Supported by a grant from the Italian Ministry of Education, University and Research-MIUR “Progetto strategico di Eccellenza Dipartimentale” #D15D18000410001 to the Department of Medical Sciences, University of Turin. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: All patients included in TR consented to registration and use of their data, which were treated and analysed in compliance with the European General Data Protection Regulation (EU GDPR), anonymizing sensitive data and processing aggregate data. ISS Data Protection Officer (DPO) authorized this study.