ABSTRACT
Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestryassociated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes.
Subject(s)
Black or African American/genetics , COVID-19/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/genetics , Influenza, Human/immunology , Leukocytes, Mononuclear/virology , White People/genetics , Adult , Aged , COVID-19/immunology , COVID-19/physiopathology , Disease Susceptibility , Gene Expression Regulation , Genetic Variation , Humans , Influenza A Virus, H1N1 Subtype/physiology , Interferon Type I/immunology , Interferon Type I/metabolism , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Quantitative Trait Loci , Severity of Illness Index , Single-Cell Analysis , Transcription, Genetic , Viral Load , Young AdultABSTRACT
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 19 its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious 20 pathogen on a susceptible population. Here, we explain the basic concepts of herd immunity and 21 discuss its implications in the context of COVID-19.