Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.