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

Abstract

Background. SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. Methods.A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID + subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID + ) or absence (n = 56 039, COVID -) of SARS-CoV-2 infection. Results. 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-DRB1*08 was more frequent in COVID + (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; P c = 0.036). In COVID + patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID + (45.5%) than COVIDpatients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03). Conclusions. Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.

Innate and adaptive immune responses to SARS-CoV-2 in humans: relevance to acquired immunity and vaccine responses

“…Several studies have examined the HLA antigenic diversity and potential susceptibility to severe SARS‐CoV‐2 infections [45–47]. This is an important consideration, as individuals who express HLA class I and/or class II molecules that have poor affinity for SARS‐CoV‐2 peptides are likely to be more prone to severe infections and develop poor or non‐sterilizing immunity after vaccination.…”

“…In an interesting paper by Amoroso et al . [47], in an Italian transplant population, the investigators found that HLA‐DRB1*O8 showed no peptide binding to SARS‐CoV‐2 peptides and, more importantly, was associated with increased mortality from SARS‐CoV‐2 [odds ratio (OR) = 2·9, 95% confidence interval (CI) = 1·15–7·21, P = 0·023]. The authors conclude that HLA antigen typing can identify individuals at higher risk for infection with SARS‐CoV‐2.…”

HLA-C*04:01 is a Genetic Risk Allele for Severe Course of COVID-19

“…It has been previously shown that specific HLA alleles were more common in patients infected with COVID-19 as compared to healthy individuals (e.g. HLA-DRB1* 15:01, HLA-DQB1* 06:02, HLA-DRB1*08, HLA-C*04:01) and it was extrapolated that these alleles may predispose to infection 31,[41][42][43] . It is not surprising that some of these alleles differed from ours, as we identified a genetic predictor specifically for severe clinical course amongst patients with COVID-19, while other groups compared healthy vs diseased.…”

HLA-A*11:01:01:01, HLA-C*12:02:02:01-HLA-B*52:01:02:02, Age and Sex Are Associated With Severity of Japanese COVID-19 With Respiratory Failure

“…The immunogenetic background of the host, such as HLA diversity, is well known to play an essential role in determining host responses to emerging infectious diseases such as TB (6), HBV (7-10), HCV (11,12), HIV (13,14), SARS-CoV-1 (15)(16)(17)(18)(19) and SARS-CoV-2 (20)(21)(22). In cases of viral infection, viruses have successfully breached the early layers of the innate defense system (early nonspecific responses) such as fever, phagocytosis and inflammation.…”