Increased Presence of Antibodies against Type I Interferons and Human Endogenous Retrovirus W in Intensive Care Unit COVID-19 Patients

In this work, we observed an increased presence of antibodies (Abs) against type I interferon (IFN-I) in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to non-ICU COVID-19 patients and healthy control (HC) subjects. Human endogenous retrovirus W (HERV-W) can reactivate after viral infection; therefore, we also investigated the presence of antibodies against HERV-W envelope (HERV-W-env)-derived epitopes. A total of 113 subjects (41 female and 72 male subjects) were analyzed. A significant difference in autoantibodies against IFN-alpha, IFN-omega, and HERV-W was observed between HCs and ICU patients; indeed, the latter have higher levels of autoantibodies against IFN-alpha, IFN-omega, and HERV-W than subjects with mild COVID-19 and HCs. Neutralizing anti-IFN-I autoantibodies may affect the ability of IFN-I to bind to the type I interferon receptor (IFNAR), blocking the activation of the antiviral response. IMPORTANCE In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia. Type I IFNs are part of a complex cross-regulatory network; however, in a small percentage of cases, the increase in autoantibodies against these proteins may lead to damage to the host instead of protection against infectious diseases.In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia.