Factors Associated with Good Patient Outcomes Following Convalescent Plasma in COVID-19: A Prospective Phase II Clinical Trial

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19. Methods: Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. Results: Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p \ 0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p \ 0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed. Conclusions: Our results suggest that convalescent plasma with adequate anti-SARS-CoV-2 antibody titer is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease. Trial Registration: ClinicalTrials.gov. Identifier, NCT04343261, IND #19805.

The Many Faces of Covid-19 at a Glance: A University Hospital Multidisciplinary Account From Milan, Italy

“…Patients treated early had a lower mortality rate and shorter hospital admission. Convalescent plasma infusion caused no adverse effects ( 72 ).…”

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

“…Limited previous clinical experiences with CP treatment in SARS-CoV, MERS, influenza, and Ebola suggest that CP may provide benefits to COVID-19 patients (Bloch et al, 2020;Devasenapathy et al, 2020). Many recent reports have documented clinical outcomes of CP treatment in severe and critically ill COVID-19 patients (Ahn et al, 2020;Ibrahim et al, 2020;Jin et al, 2020;Keith et al, 2020;Li et al, 2020a;Li et al, 2020b;Liu et al, 2020a;Madariaga et al, 2020;Maor et al, 2020;Pei et al, 2020;Perotti et al, 2020;Dwi Putera and Suci Hardianti, 2020;Shen et al, 2020a;Wang et al, 2020c;Ye et al, 2020a;Zhang et al, 2020a). Two categories of results are presented.…”

“…Among the above studies, 11 reported CP treatment in 10 or less COVID-19 patients (Ahn et al, 2020;Duan et al, 2020;Jin et al, 2020;Keith et al, 2020;Li et al, 2020a;Madariaga et al, 2020;Pei et al, 2020;Shen et al, 2020a;Wang et al, 2020c;Ye et al, 2020a;Zhang et al, 2020a). Five studies treated 37-49 patients (Ibrahim et al, 2020;Liu et al, 2020a;Maor et al, 2020;Perotti et al, 2020;Dwi Putera and Suci Hardianti, 2020). Only one randomized trial wherein 52 patients received CP treatment was reported and the results demonstrated that CP therapy plus standard treatment in severe or life-threatening COVID-19 patients did not result in significant clinical improvement (Li et al, 2020b).…”

Passive immunization and its rebirth in the era of the COVID-19 pandemic

“…Also, a similarly designed study in India [16] in a much larger group of patients showed only a limited survival benefit, although many patients with non-critical conditions experienced improved symptoms and oxygenation, and faster viral clearance relative to controls. A serious limitation of the latter study was the relatively low antibody titers (1:20-1:40) of the transferred plasma, which were much lower than in the Wuhan and Hartford studies [ 2 , 14 ].…”

“…No severe adverse effects were observed. Similarly, in a small clinical trial involving 38 patients in Hartford, CT, convalescent plasma was well tolerated, and there was moderate benefit [14] .…”