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

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 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the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data.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.

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

“…We did not observe any mild or serious transfusion-related adverse events in our patients. This is in agreement with a large cohort of COVID-19 patients receiving CP, where serious complications were rare (<1%) [ 14 , 27 ].…”

“…The latter reached only 50% of its planned enrollment due to the decrease in the number of patients admitted with COVID-19, which could have affected the outcome [ 13 ]. A recent meta-analysis that included 10 RCTs showed no association between CP and all-cause mortality or other clinical outcomes in COVID-19 patients [ 14 ]. Although these trials did not show a consistent improvement in outcome, which is most likely related to the patient population, severity of illness, time of administration, and the plasma antibody titer, they all did show that CP is safe and well-tolerated.…”

Therapeutic Use of Convalescent Plasma in COVID-19 Infected Patients with Concomitant Hematological Disorders

“…The hyperconcentrate preparation of CP appears to be useful, since it can also be administered to individuals who are poor responders to the COVID-19 vaccine and can provide an immediate neutralizing antibody response to those who are in need. Further clinical studies will help clarify the role played by CP in the immunocompromised host with COVID-19 infection and concomitant HM and will elucidate the timing (post-exposure prophylaxis, early use, late use) for its optimal use [36,37].…”

Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies

“…There are currently many doubts about the efficacy of CCP, especially on the basis of controlled studies [39][40][41], while some clinical experiences have shown a reduction in the mortality of patients with COVID-19 infection [42][43][44][45][46]. These discrepancies may be due to a quantity of bias when designing clinical studies on a disease for which there is still an incomplete knowledge [47].…”