Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study

Abstract

Background Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. Methods A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. Results An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], − 1.36; 95% CI, − 2.33 to − 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. Conclusion CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835

Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis

“…Endpoint of mortality varied among studies. Thirteen trials examined 28-day mortality [ 16 – 21 , 26 , 29 , 32 , 33 , 37 , 38 , 40 ], six trials examined 30-day mortality [ 22 , 23 , 31 , 36 , 39 , 41 ], three trials examined 60-day mortality [ 25 , 28 , 34 ] and a single trial examined 90-day mortality [ 24 ]. Three trials broadly reported in-hospital overall mortality [ 27 , 30 , 35 ].…”

“…Risk of bias assessment for individual trials is shown in Online Resource 2 and overall risk of bias in included trials is shown in Online Resource 3. The majority of included studies (22/26) were qualified as high-quality [ 16 – 19 , 26 , 28 – 34 , 37 – 41 ], fulfilling all five criteria of the RoB 2 Tool [ 11 ]. One or more criteria of the RoB 2 Tool [ 11 ] were either unclearly reported or completely missing in four studies [ 20 , 27 , 35 , 36 ], which were regarded as low-quality.…”

“…Seventeen RCT involving 16,083 patients were included in meta-analysis for need of IMV [ 16 – 20 , 23 , 24 , 26 , 28 , 30 , 31 , 33 , 37 – 41 ]. Pooling of all 17 trials showed no statistically significant benefit of CPT (RR = 1.02, 95% CI = 0.95–1.10) with unimportant heterogeneity across studies (Q(16) = 9.43, p = 0.89, I 2 = 3.30%) (Fig.…”

“…Twenty-three studies that included 19,475 patients did report 196 transfusion-related AE in 10,098 patients who actually received CPT [ 16 – 27 , 29 , 31 – 35 , 37 – 41 ], with an overall incidence rate of approximately two events per 100 patients receiving CPT. Out of these 23 studies, four trials reported that no transfusion-related AE were observed [ 18 , 23 , 25 , 34 ].…”

Convalescent plasma (hyperimmune immunoglobulin) for COVID-19 management: An update

“…With the enrolment of 101 patients with confirmed COVID-19 a randomized, single blinded, parallel, controlled study was conducted to evaluate the clinical benefits of CPT in severe COVID-19 cases [155] . The data suggested that there is increase in the nAb titre after 4 day of CPT.…”