![]() ![]() ![]() Specific focus on asymptomatic infection has the potential to further our understanding of disease pathogenesis and supports ongoing efforts towards vaccine development and the identification of potential therapeutic targets. The examination of asymptomatic infection provides a unique opportunity to consider early disease and immunological features that promote rapid viral clearance. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.ĭespite some inconsistent reporting of symptoms 1, studies have shown that at least 20% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic 2, 3, 4. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Our discovery cohort ( n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. Here, postulating that variation in the human leukocyte antigen ( HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic 1, 2, 3, 4. Nature volume 620, pages 128–136 ( 2023) Cite this article A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection ![]()
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