Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

AlQahtani, Manaf; Abdulrahman, Abdulkarim; Almadani, Abdulrahman; AlAli, Salman; Zamrooni, Alaa Mahmood Al; Hejab, Amal; Conroy, Ronán; Wasif, Pearl; Otoom, Sameer; Atkin, Stephen L.; Abduljalil, Manal

doi:10.1038/s41598-021-89444-5

Cited by 90 publications

(111 citation statements)

References 33 publications

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“…A total of 4728 records were identified from databases, websites and citation searching. There were 47 studies 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 fulfilled the inclusion criteria and were used for the systematic review and meta‐analysis (Figure 1 ). Of 47 included studies, 21 were clinical trials 16 , 17 , 18 ,…”

Section: Resultsmentioning

confidence: 99%

“…Of 47 included studies, 21 were clinical trials 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 60 , 61 , 62 and 26 were observational studies. 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 55 , 56 , 57 , 58 , 59 Among clinical trials, there were 18 studies published in peer‐reviewed journals 16 , 17 , 18 , 19 , 20 , 21 , …”

Section: Resultsmentioning

confidence: 99%

“…Ten clinical trials 16 , 17 , 21 , 22 , 23 , 25 , 31 , 32 , 33 , 61 and eleven observational studies 34 , 36 , 38 , 39 , 46 , 50 , 51 , 52 , 54 , 55 , 58 reported the length of hospital stay of CP‐treated patients and standard treatment‐treated patients. The results from meta‐analysis of peer‐reviewed clinical trials (n = 9) demonstrated that there was no significant difference between two groups with respect to the duration of hospital stay (weighted mean difference [WMD] = −1.63, 95% CI: −4.16‐0.90, P = .208, I 2 = 89.2%).…”

Section: Resultsmentioning

confidence: 99%

“…The current systemic review and meta‐analysis aimed to summarize the existing data on the efficacy of CP in COVID‐19 patients, which remains a challenge to explore treatment for SARS‐CoV‐2 pandemic to respond the increasing of the incidence of SARS‐CoV‐2 infection. According to the eligible criteria, 47 studies 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 were included and critically evaluated. Corresponding to the results of our systematic review and meta‐analysis, the CP may be effective in reducing the mortality of CP‐treated COVID‐19 patients compared with non‐CP‐treated COVID‐19 patients, especially in severe or critical patients and in Asia region.…”

Section: Discussionmentioning

confidence: 99%

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CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

Kloypan

Saesong

Sangsuemoon

et al. 2021

Eur J Clin Investigation

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Background There is still a lack of consensus on the efficacy of convalescent plasma (CP) treatment in COVID‐19 patients. We performed a systematic review and meta‐analysis to investigate the efficacy of CP vs standard treatment/non‐CP on clinical outcomes in COVID‐19 patients. Methods Cochrane Library, PubMed, EMBASE and ClinicalTrials.gov were searched from December 2019 to 16 July 2021, for data from clinical trials and observational studies. The primary outcome was all‐cause mortality. Risk estimates were pooled using a random‐effect model. Risk of bias was assessed by Cochrane Risk of Bias tool for clinical trials and Newcastle‐Ottawa Scale for observational studies. Results In total, 18 peer‐reviewed clinical trials, 3 preprints and 26 observational studies met the inclusion criteria. In the meta‐analysis of 18 peer‐reviewed trials, CP use had a 31% reduced risk of all‐cause mortality compared with standard treatment use (pooled risk ratio [RR] = 0.69, 95% confidence interval [CI]: 0.56‐0.86, P = .001, I 2 = 50.1%). Based on severity and region, CP treatment significantly reduced risk of all‐cause mortality in patients with severe and critical disease and studies conducted in Asia, pooled RR = 0.61, 95% CI: 0.47‐0.81, P = .001, I 2 = 0.0%; pooled RR = 0.67, 95% CI: 0.49‐0.92, P = .013, I 2 = 0.0%; and pooled RR = 0.62, 95% CI: 0.48‐0.80, P < .001, I 2 = 20.3%, respectively. The meta‐analysis of observational studies showed the similar results to the clinical trials. Conclusions Convalescent plasma use was associated with reduced risk of all‐cause mortality in severe or critical COVID‐19 patients. However, the findings were limited with a moderate degree of heterogeneity. Further studies with well‐designed and larger sample size are needed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

Kloypan

Saesong

Sangsuemoon

et al. 2021

Eur J Clin Investigation

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“…They plan to involve 200 EVD patients to be transfused with CP from a single individual and 100 control patients. The outcome will be measured according to all-cause mortality on day 14 following administration, and the data are not yet available [ 131 , 132 ].…”

Section: Convalescent Plasma Therapy (Cpt)mentioning

confidence: 99%

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections

Moubarak

Kasozi

Hetta

et al. 2021

Life

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Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

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Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

Janiaud

Axfors

Schmitt

et al. 2021

JAMA

221

216

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IMPORTANCE Convalescent plasma is a proposed treatment for COVID-19.OBJECTIVE To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).DATA SOURCES PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021. STUDY SELECTIONThe RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting. DATA EXTRACTION AND SYNTHESISTwo reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. MAIN OUTCOMES AND MEASURESAll-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events.RESULTS A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was −1.21% (95% CI, −5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was −2.56% [95% CI, −13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences. CONCLUSIONS AND RELEVANCETreatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

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Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

Cited by 90 publications

References 33 publications

CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections

Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19

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