Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma in severe COVID-19

In a randomized control trial on convalescent plasma therapy (CPT) in severe COVID-19, we characterized the nature, in terms of abundance of forty eight cytokines, and dimensions, in terms of their interrelationships, of the hyper-immune activation-associated ‘cytokine storm’ in patients suffering from acute respiratory distress syndrome. We found reduced plasma level of the chemokine MCP3 to be a key correlate for clinical improvement, irrespective of therapeutic regimen. We also identified an anti-inflammatory role of CPT independent of its neutralizing antibody content, and a linear regression analysis revealed that neutralizing antibodies as well as the anti-inflammatory effect of CPT both contribute to marked immediate reductions in hypoxia, as compared to patients on standard therapy.