COVID-19 convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized trial

Abstract

Background: Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. Early transfusion of high antibody titre CCP may be beneficial, especially in case of underlying immunosuppression. Methods: The CORIPLASM study was a multicentric, open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19 pneumonia, including patients with underlying immunosuppression. Patients hospitalised with COVID-19 for less than 9 days were assigned to receive 2 plasma units/day over 2 days (CCP) or usual care (UC) alone. Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) >= 6 on the 10-point scale on day 4 and survival without ventilation or additional immunomodulatory treatment by day 14. Main analysis was conducted on the whole population and a planned subgroup analysis was performed according to immunosuppression status. Findings: A total of 120 patients were recruited between April 16, 2020, and April 21, 2021, and assigned to CCP (n=60) or UC (n=60) with a 28 day-follow-up. The median time from symptoms onset to randomisation (days) was 7.0 [interquartile range (IQR) 5.0-9.0] and 7.0 [IQR 4.0-8.5] in CCP and UC, respectively. Thirteen (22%) patients with CCP had a WHO-CPS >= 6 at day 4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95% confidence interval (CI), 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0.10 -1.53]), and 7 (12%) with CCP and 12 (20%) with UC at day 28 (aHR 0.51 [95% CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in patients with underlying immunosuppression (HR 0.37 [95% CI 0.14-0.97]). Serious adverse events were noted in 30 (50%) and 26 (43%) patients with CCP or UC, respectively. Interpretation: CCP treatment did not improve early outcomes in patients with mild-to-moderate form COVID-19 pneumonia but was associated with reduced mortality in the subgroup of immunosuppressed patients. Trial registration: clinicaltrials.gov Identifier: NCT04345991

COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review

“…The literature search yielded 147 eligible studies, of which 9 controlled trials (4 randomized trials [20][21][22][23] and 5 cohort studies [24][25][26][27][28] ) were selected for meta-analysis, 13 uncontrolled large case series without individual patient data but totaling 358 patients were selected for descriptive analysis [29][30][31][32][33][34][35][36][37][38][39][40][41] , and 125 case reports/series totaling 265 patients met the eligibility criteria for individual patient data analysis, 35, . Reference 35 was included in both the descriptive analysis and the individual patient data analysis because individual patient data were available only for a subgroup of patients.…”

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

“…The process of study selection is represented in the PRISMA flow diagram (Figure 1). Three randomized clinical trials (RCTs) [28][29][30] enrolling 214 participants and 5 matched cohort studies [31][32][33][34][35] enrolling 1560 participants were included in the meta-analysis. Descriptive and exploratory analyses were performed on uncontrolled studies.…”

“…In the primary meta-analysis of the 8 controlled trials (totaling 469 patients treated with COVID-19 convalescent plasma and 1305 controls), [28][29][30][31][32][33][34][35] the key findings are summarized in Table 3, Figure 2, and eFigure 1 in the Supplement. There was a high level of concordance among study outcomes, and treatment with COVID-19 convalescent plasma was associated with reduced risk of mortality according to the pooled risk ratio of 0.63 (95% CI, 0.50 to 0.79) and the pooled risk difference of −0.10 (95% CI, −0.15 to −0.06).…”

Immune Plasma for the Treatment of COVID-19: Lessons Learned so far

“…49 Two further randomized trials which included a subgroup of immunosuppressed patients are available only as congress abstracts or preprints so far. 71,72 A total of 133 patients were included in the German RECOVER trial (NCT05200754), 71 patients with hematological malignancies, other cancers, or immunosuppression. Patients were randomized (1:1) to receive standard therapy alone or with CCP.…”

“…In contrast, the subgroup of 49 patients with hemato-oncologic disease showed a significant survival advantage for the CCP group (HR: 0.37; CI: 0.14-0.97). 72 An updated meta-analysis of CCP for the treatment of immunocompromised patients with COVID-19 by Senefeld and colleagues included 9 controlled studies (535 treated patients and 1,365 controls, including 4 randomized controlled trials), an individual patient data analysis of 125 case reports/series (265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (358 patients). The meta-analysis of controlled studies showed a mortality risk ratio of 0.65 comparing treatment with CCP versus standard of care for immunosuppressed COVID-19 patients.…”