Clinical Trial Subgroup Analyses to Investigate Clinical and Immunological Outcomes of Convalescent Plasma Therapy in Severe COVID-19.

Abstract

ObjectiveTo assess clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT) we performed sub-group analyses on a completed randomised control trial (RCT) on CPT in severe COVID-19.PatientsA series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed RCT (Clinical Trial Registry of India, No. CTRI/2020/05/025209).MethodsThe subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed randomized control trial. Data on the plasma abundance of a large panel of cytokines from the same cohort of patients were also utilised to characterize the heterogeneity of the putative anti-inflammatory function of convalescent plasma (CP) in addition to passively providing neutralizing antibodies.ResultsWhile across all age-groups primary clinical outcomes were not significantly different in the RCT, significant immediate mitigation of hypoxia, reduction in hospital stay as well as significant survival benefit were registered in younger (<67 years in our cohort) severe COVID-19 patients with ARDS on receiving CPT. In addition to neutralizing antibody content of convalescent plasma, its anti-inflammatory proteome on attenuation of systemic cytokine deluge, significantly contributed to the clinical benefits of CPT.ConclusionThe sub-group analyses revealed that clinical benefit of CPT in severe COVID-19 is linked to the anti-inflammatory protein content of CP, apart from the anti-SARS-CoV-2 neutralizing antibody content.