Perrine Janiaud1, Cathrine Axfors2,3, Andreas M Schmitt1,4, Viktoria Gloy1, Fahim Ebrahimi5, Matthias Hepprich6,7, Emily R Smith8, Noah A Haber2, Nina Khanna9, David Moher10, Steven N Goodman2,11,12, John P A Ioannidis2,11,12,13,14,15, Lars G Hemkens1,2,15. 1. Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 2. Meta-Research Innovation Center at Stanford, Stanford University, Stanford, California. 3. Department for Women's and Children's Health, Uppsala University, Uppsala, Sweden. 4. Department of Medical Oncology, University of Basel, Basel, Switzerland. 5. Department of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland. 6. Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland. 7. Clinic of Endocrine and Metabolic Disorders, Cantonal Hospital Olten, Olten, Switzerland. 8. Milken Institute School of Public Health, Department of Global Health, George Washington University, Washington, DC. 9. Division of Infectious Diseases and Hospital Hygiene and Infection Biology Laboratory, University Hospital Basel, University of Basel, Basel, Switzerland. 10. Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. 11. Department of Medicine, School of Medicine, Stanford University, Stanford, California. 12. Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, California. 13. Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, California. 14. Department of Statistics, School of Humanities and Sciences, Stanford University, Stanford, California. 15. Meta-Research Innovation Center Berlin, Berlin Institute of Health, Berlin, Germany.
Abstract
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 Selection: The 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 Synthesis: Two 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 Measures: All-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 Relevance: Treatment 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.
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 Selection: The 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 Synthesis: Two 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 Measures: All-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 Relevance: Treatment 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.
Authors: Ferdinand Velasco; Donghan M Yang; Minzhe Zhang; Tanna Nelson; Thomas Sheffield; Tony Keller; Yiqing Wang; Clark Walker; Chaitanya Katterapalli; Kelli Zimmerman; Andrew Masica; Christoph U Lehmann; Yang Xie; John W Hollingsworth Journal: J Hosp Med Date: 2021-11 Impact factor: 2.960
Authors: Shanna A Arnold Egloff; Angela Junglen; Joseph Sa Restivo; Marjorie Wongskhaluang; Casey Martin; Pratik Doshi; Daniel Schlauch; Gregg Fromell; Lindsay E Sears; Mick Correll; Howard A Burris; Charles F LeMaistre Journal: J Clin Invest Date: 2021-10-15 Impact factor: 14.808
Authors: Marliana S Rejeki; Nana Sarnadi; Retno Wihastuti; Vininta Fazharyasti; Wisvici Y Samin; Frilasita A Yudhaputri; Edison Johar; Neni Nurainy; Novilia S Bachtiar; David H Muljono Journal: EClinicalMedicine Date: 2021-06-04
Authors: Michael J Joyner; Nigel Paneth; Rickey E Carter; Arturo Casadevall; Quigly Dragotakes; Patrick W Johnson; Jonathon W Senefeld; Stephen A Klassen; R Scott Wright Journal: Elife Date: 2021-06-04 Impact factor: 8.140
Authors: Koen K A Van Rompay; Katherine J Olstad; Rebecca L Sammak; Joseph Dutra; Jennifer K Watanabe; Jodie L Usachenko; Ramya Immareddy; Anil Verma; Yashavanth Shaan Lakshmanappa; Brian A Schmidt; Jamin W Roh; Sonny R Elizaldi; A Mark Allen; Frauke Muecksch; Julio C C Lorenzi; Sarah Lockwood; Rachel E Pollard; JoAnn L Yee; Peter B Nham; Amir Ardeshir; Jesse D Deere; Jean Patterson; Que Dang; Theodora Hatziioannou; Paul D Bieniasz; Smita S Iyer; Dennis J Hartigan-O'Connor; Michel C Nussenzweig; J Rachel Reader Journal: PLoS Pathog Date: 2021-07-06 Impact factor: 6.823