Abstract
Sardinia has one of the lowest incidences of hospitalization and related mortality in Europe and yet a very high frequency of the Neanderthal risk locus variant on chromosome 3 (rs35044562), considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 SARS-CoV-2 patients and 314 healthy Sardinian controls. One hundred and twenty patients were asymptomatic, 90 were pauci-symptomatic, 108 presented a moderate disease course and 40 were severely ill. All patients were analyzed for the Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness. The β°39 C>T Thalassemia variant (rs11549407 ) , HLA haplotypes, KIR genes, KIRs and their HLA class I ligand combinations were also investigated. Our findings revealed an increased risk for severe disease in Sardinian patients carrying the rs35044562 high risk variant [OR 5.32 (95% CI 2.53 – 12.01), p = 0.000]. Conversely, the protective effect of the HLA-A*02:01, B*18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 – 41.0), p < 0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.
Keywords: B*18:01; COVID-19; DRB*03 extended haplotype; HLA-A*02:01; Neanderthal Covid-19 risk haplotype; SARS-CoV-2; rs35044562 variant.
【저자키워드】 COVID-19, SARS-CoV-2, B*18:01, DRB*03 extended haplotype, HLA-A*02:01, Neanderthal Covid-19 risk haplotype, rs35044562 variant., 【초록키워드】 Evolution, Europe, Mortality, Hospitalization, Vaccines, variant, Infection, Sardinian population, risk, drug, outcome, risk factor, Asymptomatic, Patient, Genetic variant, KIR, incidence, mechanism, protective effect, Protective, Haplotype, HLA-A*02:01, Combination, Ligand, Frequency, severe disease, HLA class I, high risk, balance, chromosome 3, HLA-A, Sardinia, SARS-CoV-2 disease, locus, chromosome, 95% CI, increased risk, moderate disease, carriers, disease course, combinations, KIR genes, KIRs, severe SARS, pauci-symptomatic, thalassemia, Neanderthal, carrier, HLA haplotypes, severe SARS-CoV-2, lowest, Course, shown, predicted, analyzed, healthy, reported, investigated, evaluated, turn, Sardinian, immunogenetic factor, Sardinian controls, SARS-CoV-2 patient, three-loci extended haplotype, 【제목키워드】 Population, HLA, Major, Factor, Sardinian, Extended,