Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial

ObjectivesEfficacy of convalescent plasma in COVID-19 pneumonia (CPP) is uncertain, especially in immunocompromised patients. CORIMUNO-CORIPLASM is an open-label, Bayesian randomised clinical trial embedded in the CORIMUNO trials platform that evaluated the efficacy of CCP in patients with moderate COVID-19. Setting19 university and general hospitals across France. ParticipantsAdult hospitalized with a positive SARS-CoV2 test, duration of symptoms < 9 days and WHO score severity 4 or 5 who signed written inform consent. InterventionOpen label randomisation to either usual care (UC) or 4 units (200-220 ml/unit, 2 units/day over 2 consecutive days) of convalescent plasma (CCP) with a seroneutralisation titer > 40. OutcomesPrimary outcome was proportion of patients with a WHO-Clinical Progression Score (CPS) [&ge;]6 on the 10-point scale on day (d) 4 (higher values indicating a worse outcome) and survival without ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes included evolution of WHO-CPS, overall survival, time to discharge and time to oxygen supply independency. Pre-defined subgroups analyses included immunosuppression status, duration of symptoms before randomization and use of steroids. ResultsA total of 120 patients were recruited and assigned to CCP (n=60) or UC (n=60), including 22 (CCP) and 27 (UC) immunocompromised patients. Thirteen (22%) patients with CCP had a WHO-CPS [&ge;]6 at day 4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95%CrI 0.71 to 5.24]. By day 14, 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 day 14 (aHR 0.40 [95%CrI 0{middle dot}10 -1{middle dot}53]), and 7 (12%) with CCP and 12 (20%) with UC at day 28 (aHR 0.51 [95%CrI 0.20-1.32]). I n a s ubgroup analysis performed in immunocompromised patients, the association of CCP with mortality was HR 0.39 [95%CI 0.14-1.10]. ConclusionsCCP did not improve early outcomes in patients with moderate COVID-19. Its efficacy in immunocompromised patients needs to be further explored. Trial registrationclinicaltrials.gov Identifier: NCT04345991 KEY MESSAGES BOXO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LIConvalescent plasma treatment, i.e., passive polyclonal antibody administration to provide immediate immunity, has been used to improve the survival rate of patients with severe acute respiratory syndromes of viral etiology in emergency settings and times where there was no specific antiviral treatment C_LIO_LIAt the early stages of the COVID-19 pandemic, using high titre COVID-19 convalescent plasma (CCP) appeared to be an immediate therapeutic option. C_LIO_LIHowever, a large number of randomised clinical trials and observational studies have yielded conflicting results regarding the efficacy of CCP. C_LIO_LIFurthermore, the efficacy of CCP in patients with underlying immunosuppression has been evaluated only in a limited manner. C_LIO_LIThe emergence of variants resistant to other passive immunotherapy approaches, ie monoclonal antibodies, has limited the therapeutics options for such patients C_LI What this study adds ?O_LIThis multicentre randomised clinical trial provided evidence that high titre CCP in a population hospitalised with a mild to moderate form of COVID-19 within 9 days of symptoms onset may not improve early outcome. C_LIO_LIIn the subgroup of patients with immunosuppression, there was evidence suggesting a lower odds of death 14 and 28 days after CCP transfusion, albeit without reaching significance. C_LI How does this study might affect research, practice of policyO_LIThe result of study, along with the recent data obtained from other trials and cohort studies supports further evaluation of CCP transfusion in patients with underlying immunosuppression for whom therapeutic options are currently scarce if non-existent, due to the ever changing genetic variability of SARS-CoV2. C_LI