This study examined autoimmune antibodies to annexin A2, which is a phospholipid-binding protein expressed in the lung and other organs, in COVID-19 patients. Annexin A2 is critical for fibrinolysis, lung elasticity, cell membrane repair, and integrity of the pulmonary vasculature. Therefore, antagonism of annexin A2 may explain many of the clinical features of severe COVID-19 cases. This study analyzed plasma from 86 patients who were hospitalised for COVID-19 and confirmed to be positive by PCR. Anti-annexin A2 IgG antibodies were measured by ELISA. They also studied IgG antibodies directed against annexin A5, which is another target of prothrombotic antiphospholipid antibodies, for comparison. Antibody levels were calculated using a plasma sample previously identified as a high responder for IgG autoantibodies. The data from this study predicted mortality based on anti-annexin A2 antibody levels.