Nature and dimensions of the systemic hyper-inflammation and its attenuation by convalescent plasma in severe COVID-19

Novel coronavirus SARS-CoV2, causing coronavirus disease 2019 or COVID-19, led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to a severe disease with acute respiratory distress syndrome (ARDS) and an associated systemic hyper-inflammation. First to characterize key cytokines and their dynamics in this hyper-inflammatory condition, we assessed abundance and correlative expression of a panel of forty eight cytokines in patients progressing to ARDS, as compared to patients with mild disease. Then in an ongoing randomized control trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics, as a correlate for the level of hypoxia experienced by the patients. We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. Neutralizing antibodies as well as reductions in circulating interleukin-6 and interferon gamma induced protein 10, contributed to marked rapid reductions in hypoxia in response to CPT.