2025-07-092025-07-092022-08-04Sironi, M., Cagliani, R., Biasin, M., Lo Caputo, S., Saulle, I., Forni, D.,...,Clerici, M. (2022). No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals. PNas Nexus, 1 (3), pgac138/1-4. https://doi.org/10.1093/pnasnexus/pgac138.2752-6542https://hdl.handle.net/11441/175180An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was in herited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection.We thus expectedthisallele to beover-represented in highly exposedindividuals whoremainuninfected(exposedseroneg ative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to de tect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype sta tus. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.application/pdf4 p.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/HIVCOVID-19Genetic risk factorExposed seronegative individualsinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1093/pnasnexus/pgac138