Autoantibodies Against Type I Interferons are a Prominent Feature in SARS-CoV-2 Fatal Disease and Hospitalization

COVID-19 affects people differently. Some recover quickly, while others become very sick or die. Scientists have found that some COVID-19 patients develop autoantibodies, or "self-attacking" antibodies. How and which autoantibodies were relevant in COVID-19 remains to be described. This study conducted in Manaus, Brazil, aimed to understand if these autoantibodies contributed to severe COVID-19 and poor survival outcomes. Manaus was one of the hardest-hit regions by the pandemic. We studied 435 COVID-19 patients (263 hospitalized, 172 nonhospitalized), and 37 healthy individuals. Blood samples were collected over 28 days and tested for 20 different autoantibodies and antibodies against the coronavirus using advanced laboratory assays. Hospitalized patients had notably higher levels of 2 specific autoantibodies. Those that block the body's natural antiviral proteins (type I interferons) and ACE2 (helps regulate systemic and local inflammation, and fluid homeostasis). These autoantibodies were strongly linked with severe illness and a higher risk of death, and increased over time. Patients with strong autoantibody responses also had higher levels of antibodies against the virus, suggesting a link between infection and immune self-attack. Autoantibodies were strongly linked to severe COVID-19 and death. Screening for them could help doctors identify high-risk patients early for effective treatment strategies.