Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

Abstract

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

“…A total of 19 studies [ 17 , 19 , 22 , 41 , 43 , 44 , 47 – 49 , 51 , 52 , 57 , 60 , 63 , 68 , 70 , 73 , 77 , 81 ] ( N = 26,912) reported the incidence of progression to invasive mechanical ventilation and/or ECMO and were included in the NMA. No intervention was associated with significant reductions in the odds of invasive mechanical ventilation/ECMO (see Fig.…”

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials

“…Among all the included studies, 4 studies ( 24 , 28 , 34 , 48 ) were preprinted and 28 studies ( 16 – 18 , 25 – 27 , 29 – 33 , 35 – 47 , 49 – 52 ) were published in peer-reviewed journals. 10 studies ( 24 , 26 , 31 , 38 , 41 , 43 , 44 , 46 , 50 , 51 ) were double-blind RCTs with placebo and 22 studies ( 16 – 18 , 25 , 27 – 30 , 32 – 37 , 39 , 40 , 42 , 45 , 47 – 49 , 52 ) were designed as open-label trials. All trials included patients with confirmed Covid-19 except for the RECOVERY trial ( 35 ), which included both suspected and confirmed COVID-19 patients.…”

“…8 studies ( 26 , 35 , 38 , 41 , 43 , 44 , 46 , 50 ) were regarded as low risk of bias, and 16 studies ( 16 – 18 , 25 , 27 , 29 , 30 , 32 , 37 , 39 , 40 , 42 , 45 , 47 , 49 , 52 ) contained potential performance bias for the open-label design. 4 studies were considered as containing potential bias due to early termination ( 31 , 33 , 36 , 51 ). Notably, although no high risks of bias in D1-D5, 4 studies ( 24 , 28 , 34 , 48 ) were classified as high risk for pre-printed and lack of peer review.…”

A review of mass spectrometry‐based analyses to understand COVID‐19 convalescent plasma mechanisms of action

“…In contrast, results of a randomized clinical trial of CCP treatment in hospitalized COVID‐19 patients with moderate to severe disease showed no clinical improvement relative to the placebo, providing support against the use of CCP treatment for COVID‐19 pneumonia (van den Berg et al., 2022 ). The results from a randomized controlled, open‐label, platform trial also showed no improvement in survival or other clinical outcomes in hospitalized COVID‐19 patients treated with high‐titer CP (RECOVERY Collaborative Group, 2021a ).…”

“…The results from a randomized controlled, open‐label, platform trial also showed no improvement in survival or other clinical outcomes in hospitalized COVID‐19 patients treated with high‐titer CP (RECOVERY Collaborative Group, 2021a ). Indeed, CCP can be used for either prophylaxis of infection or treatment of disease (Casadevall & Pirofski, 2020 ), however as highlighted above (Duan et al., 2020 ; Shen et al., 2020 ; van den Berg et al., 2022 ), and by other experts in the field (Dzik, 2020 ), it is important to conduct additional studies and randomized controlled investigations to confirm the effectiveness and safety of using CCP in all types of COVID‐19 hospitalized patients, particularly for those at risk of progressing to critical state. For example, Allahyari et al.…”