HLA class I associations with the severity of COVID-19 disease in the United Arab Emirates

Abstract

SARS-CoV-2 appears to induce diverse innate and adaptive immune responses, resulting in different clinical manifestations of COVID-19. Due to their function in presenting viral peptides and initiating the adaptive immune response, certain Human Leucocyte Antigen (HLA) alleles may influence the susceptibility to severe SARS-CoV-2 infection. In this study, 92 COVID-19 patients from 15 different nationalities, with mild (n = 30), moderate (n = 35), and severe (n = 27) SARS-CoV-2 infection, living in the United Arab Emirates (UAE) were genotyped for the Class I HLA -A, -C, and -B alleles using next-generation sequencing (NGS) between the period of May 2020 to June 2020. Alleles and inferred haplotype frequencies in the hospitalized patient group (those with moderate to severe disease, n = 62) were compared to non-hospitalized patients (mild or asymptomatic, n = 30). An interesting trend was noted between the severity of COVID-19 and the HLA-C*04 (P = 0.0077) as well as HLA-B*35 (P = 0.0051) alleles. The class I haplotype HLA-C*04-B*35 was also significantly associated (P = 0.0049). The involvement of inflammation, HLA-C*04, and HLA-B*35 in COVID-19 severity highlights the potential roles of both the adaptive and innate immune responses against SARS-CoV-2. Both alleles have been linked to several respiratory diseases, including pulmonary arterial hypertension along with infections caused by the coronavirus and influenza. This study, therefore, supports the potential use of HLA testing in prioritizing public healthcare interventions for patients at risk of COVID-19 infection and disease progression, in addition to providing personalized immunotherapeutic targets.

Establishing association between HLA‐C*04:01 and severe COVID‐19

“…10 Statistical significance in this early analysis was marginal, and we had cautioned our readers about the interpretability of association results derived from a limited COVID-19 patient cohort size, advocating for larger patient cohorts from diverse communities. 11 Since our initial report, 10 several studies have recapitulated associations of HLA-C*04:01 and A*11:01 alleles with COVID-19 severity (reviewed in References 12,13), including a validation of our findings on the New York cohort data, 14 but also extending to patient cohorts across the globe including Europe, 15 India, 16 Armenia, 17 Spain, 18 and the United Arab Emirates 19 (Figure 1).…”