Severe SARS-CoV-2 infection is linked to the presence of autoantibodies against multiple targets, including phospholipids and type-I interferons. We recently identified activation of an autoimmune-prone B cell response pathway as correlate of severe COVID-19, raising the possibility of de novo autoreactive antibody production during the antiviral response. Here, we identify autoreactive antibodies as a common feature of severe COVID-19, identifying biomarkers of tolerance breaks that may indicate aggressive immunomodulation.