Genetics shape who survives infections once thought harmless

A Nature News feature explains that inherited immune-system mutations—and, more recently, autoantibodies against interferons—help determine why some people die from microbes that are usually harmless. Researchers have cataloged hundreds of inborn errors of immunity (IEIs) across many genes, with defects like interferon-γ receptor mutations causing severe mycobacterial disease, and autoantibodies linked to severe COVID-19 and other infections. Some mutations can even confer protection against specific pathogens (e.g., CCR5 against HIV). With incomplete penetrance and epigenetic regulation, IEIs can vary by cell type and over a person’s lifetime, prompting genetic screening and targeted therapies to prevent or treat severe infections.