Why do people die from COVID19? For illuminating factors that underlie varied susceptibilities to the disease, Paul Bastard is the grand prize winner of the inaugural Michelson Philanthropies & Science Prize for Immunology.
). In patients with critical COVID-19, 10% had immunoglobulin G auto-Abs that neutralized high amounts of IFN-ω and/or the 13 individual types of IFN-α. Further, these auto-Abs prevented IFN-α2 from blocking SARS-CoV-2 in vitro.
In autoimmune polyglandular syndrome type-1 , affected individuals produce auto-Abs against type I IFNs from early childhood onward. Among a group of APS-1 patients, aged 8 to 48 years, infected with SARS-CoV-2, we found that most were hospitalized for COVID-19 pneumonia, with a fatal outcome for 18% .
The findings outlined here provide clues to the reasons why COVID-19 is fatal for some individuals 70 years and older . The presence of preexisting auto-Abs against type I IFNs can account for severe disease in some older individuals, as it does in many younger patients presenting with life-threatening COVID-19.