Journal Article

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

Davide Firinu, Luigi Isaia Lecca, Stefano Mocci, Luchino Chessa, Selene Cipri, Mauro Giovanni Carta, Roberto Littera, Erika Giuressi, Carla Maria Ottelio, Sabrina Giglio, Andrea Perra, Alessia Mascia, Michela Miglianti, Maurizio Melis, Celeste Sanna, Stefania Rassu, Federica Cannas, Marcello Campagna, Ignazio S. Piras, Francesca Sedda, Sara Lai, Monica Vacca, Daniele Schirru, Stefania Tranquilli

2023

Overview

A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). HLA-G locus analysis showed that the extended haplotype was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant polymorphism ( ) shows that the genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait ( C>T in the gene), -C C1+ group combination and the haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal gene variant ( A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, genotype was independent from the other significant variables [OR = 0.4 (95% CI 0.2 - 0.7), P = 6.5 x 10 ]. Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: 3' Untranslated Regions / 3' Untranslated Regions - genetics / Asymptomatic / COVID-19 / COVID-19 - genetics / COVID-19 vaccines / COVID-19; Sardinian population; Soluble HLA-G; HLA-G 3’UTR haplotypes; KIR2DS2; Gene; Neanderthal LZTFL1 variants / Disease / Drb1 protein / Epidemics / Ethics / Gene Frequency / Gene polymorphism / Genes / Genetic diversity / Genetic factors / Haplotypes / HBB gene / Histocompatibility antigen HLA / HLA-G 3’UTR haplotypes / HLA-G Antigens / HLA-G Antigens - genetics / Hospitals / Humans / Immune response / Immune system / Immunologic diseases. Allergy / Immunology / Immunomodulation / Influence / Informed consent / KIR2DS2 gene / Leukocytes / Lztfl1 gene / neanderthal LZTFL1 variants / Patients / Polymorphism / Potassium channels (inwardly-rectifying) / RC581-607 / Sardinian population / SARS-CoV-2 / SARS-CoV-2 - genetics / Severe acute respiratory syndrome coronavirus 2 / soluble HLA-G / Thalassemia / Viral infections