RESUMEN
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.
Asunto(s)
Negro o Afroamericano/genética , COVID-19/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/genética , Gripe Humana/inmunología , Leucocitos Mononucleares/virología , Población Blanca/genética , Adulto , Anciano , COVID-19/inmunología , COVID-19/fisiopatología , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Variación Genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Interferón Tipo I/inmunología , Interferón Tipo I/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Sitios de Carácter Cuantitativo , Índice de Severidad de la Enfermedad , Análisis de la Célula Individual , Transcripción Genética , Carga Viral , Adulto JovenRESUMEN
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.