A Systematic Review and Meta-Analysis of an Emerging Therapy against COVID-19: Is Convalescent Plasma a Hidden Gem Not Yet Optimized?

Abstract

Background: An unprecedented global effort in identifying potentially viable and emerging drugs for effective treatment of the novel coronavirus disease (2019) is being made. Of the most promising candidate therapies, convalescent plasma (CP), albeit controversial, is approved for emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA). The concept rests on passive immunity, achieved by administering plasma with high titers of neutralizing antibodies to reduce severity of SARS-CoV-2 infection and mortality. The aim of this paper is to assess the clinical improvement, patients’ discharge status and all-cause mortality in convalescent plasma versus standard of care COVID-19 patient groups. Methods: Using PRISMA guidelines, a review was conducted from January, 2020, until October, 2020 employing keywords including “convalescent plasma”, “clinical improvement, “mortality”, “adverse events”, “viral load”, “dosing”, and survival.” Dichotomous data for all-cause mortality, patients’ discharge status, and clinical improvement at day 14 of treatment were meta-analyzed applying the Mantel-Haenszel (M-H) random effects model using Review Manager 5.4.  Results: A total of 627 (23.9%) patients in the CP group and 1997 (76.1%) patients in the control group were pooled. The studies were conducted in the United States, China, Netherlands, and Iran. The CP group had a lower association to all-cause mortality as compared to the control group [OR: 0.69; CI: 0.50 to 0.96; P=0.03]. Patients who received CP had higher probability of discharge during the study course [OR: 1.87; CI: 1.1 to 3.18; P=0.02]. Bias was expected in the analysis due to the stratified of study designs included. Conclusion: Convalescent plasma therapy may be an effective and vital tool with promising historical, current, and expected clinical trial evidence of metrics such as increased safety and reduction of all-cause mortality.