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

Objectives Efficacy 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. Setting 19 university and general hospitals across France. Participants Adult hospitalized with a positive SARS-CoV2 test, duration of symptoms < 9 days and WHO score severity 4 or 5 who signed written inform consent. Intervention Open 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. Outcomes Primary outcome was proportion of patients with a WHO-Clinical Progression Score (CPS) ≥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. Results A 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 ≥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 0·10 -1·53]), 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]. Conclusions CCP did not improve early outcomes in patients with moderate COVID-19. Its efficacy in immunocompromised patients needs to be further explored. Trial registration [clinicaltrials.gov][1] Identifier: [NCT04345991][2] What is already known on this topic? What this study adds ? How does this study might affect research, practice of policy ### Competing Interest Statement PT, PM and AF are employees of Etablissement Francais du Sang (EFS), the French public transfusion service, which collects, manufactures, tests and issues all blood components in France. All other co-authors declare no competing interests related to the topic of the study. ### Clinical Trial Clinicaltrials.gov Identifier: [NCT04345991][2] ### Funding Statement Programme Hospitalier de recherche Clinique (DGOS-French Ministry of Health), Fondation pour la Recherche Medicale, Sorbonne Universite AAP 2020, Emergency Support Instrument (ESI), DG Sante, European Commission. A CC-BY public copyright license (CC-BY 4.0 https://creativecommons.org/licenses/by/4.0/) has been applied by the authors to the present document and will be applied to all subsequent versions up to the Author Accepted Manuscript arising from this submission, in accordance with the grant open access conditions. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical clearance was obtained from Comite de Protection des Personnes (CPP) Ile de France VI on April 10, 2020 (no. 26-20 Med.1) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data for this article will be made available after publication on request from any qualified researchers or academicians. The data include: analysed deidentified participant data, data dictionary, study protocol, statistical analysis plan, and the informed consent form, among other data. The data will be shared for 2 years after publication upon receipt of a request sent to raphael.porcher{at}aphp.fr. [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04345991&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F05%2F2022.08.09.22278329.atom