Mortality Benefit of Convalescent Plasma in COVID-19: A Systematic Review and Meta-Analysis

Abstract

Importance/Background: With a scarcity of high-grade evidence for COVID-19 treatment, researchers and health care providers across the world have resorted to classical and historical interventions. Immunotherapy with convalescent plasma (CPT) is one such therapeutic option.Methods: A systematized search was conducted for articles published between December 2019 and 18th January 2021 focusing on convalescent plasma efficacy and safety in COVID-19. The primary outcomes were defined as mortality benefit in patients treated with convalescent plasma compared to standard therapy/placebo. The secondary outcome was pooled mortality rate and the adverse event rate in convalescent plasma-treated patients.Results: A total of 27,706 patients were included in the qualitative analysis, and a total of 3,262 (2,127 in convalescent plasma-treated patients and 1,135 in the non-convalescent plasma/control group) patients died. The quantitative synthesis in 23 studies showed that the odds of mortality in patients who received plasma therapy were significantly lower than those in patients who did not receive plasma therapy [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.53–0.80, p < 0.0001, I2 = 15%). The mortality benefit remains the same even for 14 trials/prospective studies (OR 0.59, 95% CI 0.43–0.81, p = 0.001, I2 = 22%) as well as for nine case series/retrospective observational studies (OR 0.78, 95% CI 0.65–0.94, p = 0.01, I2 = 0%). However, in a subgroup analysis for 10 randomized controlled trials (RCTs), there was no statistically significant reduction in mortality between the CPT group compared to the non-CPT group (OR 0.76, 95% CI 0.53–1.08, p = 0.13, I2 = 7%). Furthermore, the sensitivity analysis of 10 RCTs, excluding the study with the highest statistical weight, displayed a lower mortality rate compared to that of non-CPT COVID-19 patients (OR 0.64, 95% CI 0.42–0.97, p = 0.04, I2 = 0%). The observed pooled mortality rate was 12.9% (95% CI 9.7–16.9%), and the pooled adverse event rate was 6.1% (95% CI 3.2–11.6), with significant heterogeneity.Conclusions and Relevance: Our systemic review and meta-analysis suggests that CPT could be an effective therapeutic option with promising evidence on the safety and reduced mortality in concomitant treatment for COVID-19 along with antiviral/antimicrobial drugs, steroids, and other supportive care. Future exploratory studies could benefit from more standardized reporting, especially in terms of the timing of interventions and clinically relevant outcomes, like days until discharge from the hospital and improvement of clinical symptoms.

The Effectiveness of Convalescent Plasma for the Treatment of Novel Corona Virus Disease 2019: A Systematic Review and Meta-Analysis

“…Similarly, the study conducted by Janiaud et al ( 40 ) involving a total of 11,782 patients from 10 RCTs indicated that CP was not associated with a decrease in all-cause mortality or any benefit for other clinical outcomes. The other two meta-analysis showed a reduction in mortality but disappeared in RCTs, strengthening our results ( 41 , 42 ). Contrary to our study, several previous meta-analyses ( 43 – 46 ) showed that CP could help reduce mortality in COVID-19 patients, and their level of evidence was lower than the present study because most of them included not only RCTs but also observation studies in their analysis.…”

An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment

“…The initial results were very promising, but the intervention group not only included COVID-19 patients, but also those with SARS, MERS, and influenza ( Aviani et al, 2021 ). In a meta-analysis of COVID-19 patients, Bansal et al, showed that adding convalescent plasma to the standard of care reduced mortality among patients ( Bansal et al, 2021a ). A second meta-analysis by Janiaud et al, did not demonstrate the beneficial effect of administering convalescent plasma to patients ( Janiaud et al, 2021 ).…”

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

“…Most recently, the US Food and Drug Administration (FDA) granted Emergency Use Authorization for two neutralizing antibody cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab), as well as monotherapy with bamlanivimab for treatment of ambulatory patients who have a high risk of progressing to severe disease [6]. On the other hand, individual randomized control trials on the efficacy of convalescent plasma (CP) have shown negative results [7][8][9][10][11][12][13][14][15][16][17]; however, two recent meta-analyses have demonstrated the efficacy of convalescent plasma (CP) in mortality reduction of patients with severe COVID-19, similarly to the results of several matchedcontrol trials [18,19]. A survival benefit of patients treated with CP was recently shown by our group in a matched propensity score analysis of 59 patients [20].…”