Effect of time and titer in convalescent plasma therapy for COVID-19

Paola De Candia,Francesco Prattichizzo,Silvia Garavelli,Rosalba La Grotta,Annunziata De Rosa,Agostina Pontarelli,Roberto Parrella,Antonio Ceriello,Giuseppe Matarese

doi:10.1016/j.isci.2021.102898

Abstract

SummaryThe clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22). On the other hand, the benefit on mortality was not increased by using plasma with a high-antibody titer compared with unselected plasma. This meta-analysis might promote CP usage in patients with early-stage COVID-19 in further RCTs to maximize its benefit in decreasing mortality, especially in less affluent countries.

Highlights

Coronavirus disease (COVID)-19 has affected more than 180,000,000 subjects and caused almost 4,000,000 deaths, as of July 1st, 2021, according to the Coronavirus Resource Center at Johns Hopkins University
Our results show that, when provided at early stages of the disease, convalescent plasma (CP) significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22)
This meta-analysis might promote CP usage in patients with early-stage coronavirus disease (COVID)-19 in further randomized clinical trials (RCTs) to maximize its benefit in decreasing mortality, especially in less affluent countries

Summary

Introduction

Coronavirus disease (COVID)-19 has affected more than 180,000,000 subjects and caused almost 4,000,000 deaths, as of July 1st, 2021, according to the Coronavirus Resource Center at Johns Hopkins University. In circumstances in which the virus induces an immune response entailing the production of neutralizing antibodies, the collection of plasma from a convalescent donor and its passive transfusion to another patient (an approach known since the beginning of 1900) (Marson et al, 2020) has proven to be a powerful and feasible therapeutic strategy for the clearance of viremia (Mair-Jenkins et al, 2015). The use of plasma from convalescent patients with COVID-19 was proposed from the very beginning as a treatment to halt virus progression and promote favorable outcomes (Chen et al, 2020) and authorized by the Food and Drug Administration (FDA) as an investigational drug for contrasting the novel pathogen (https://www.fda.gov/vaccines-blood-biologics/investigational-newdrug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19convalescent-plasma).

Results

Discussion

Conclusion