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BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1â¯year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.
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Doadores de Sangue , Sorodiagnóstico da Sífilis , Sífilis , Humanos , Doadores de Sangue/estatística & dados numéricos , Sífilis/epidemiologia , Sífilis/diagnóstico , Sífilis/sangue , Masculino , França/epidemiologia , Feminino , Adulto , Prevalência , Fatores de Risco , Sorodiagnóstico da Sífilis/métodos , Pessoa de Meia-Idade , Treponema pallidum/imunologia , Treponema pallidum/isolamento & purificação , Estudos Soroepidemiológicos , Adulto Jovem , Homossexualidade Masculina/estatística & dados numéricosRESUMO
Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.
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BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.
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Imunoglobulinas Intravenosas , Humanos , Inquéritos e Questionários , Imunoglobulinas Intravenosas/uso terapêutico , Austrália , Canadá , Hospitais/estatística & dados numéricos , Japão , Estados Unidos , Bancos de Sangue/provisão & distribuição , Bancos de Sangue/estatística & dados numéricosRESUMO
BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).
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Autoanticorpos , Doenças Autoimunes , Adulto , Humanos , Predisposição Genética para Doença , Genótipo , Cadeias HLA-DRB1/genética , Infecções por Mycobacterium não TuberculosasRESUMO
The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.
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COVID-19 , Humanos , COVID-19/terapia , Soroterapia para COVID-19 , SARS-CoV-2 , Imunização Passiva , Hospedeiro Imunocomprometido , Anticorpos Antivirais/uso terapêutico , Anticorpos NeutralizantesRESUMO
BACKGROUND AND OBJECTIVES: Until recently, gay, bisexual and other men who have sex with men (MSM) were deferred from donating blood for 3-12 months since the last male-to-male sexual contact. This MSM deferral has been discontinued by several high-income countries (HIC) that now perform gender-neutral donor selection. MATERIALS AND METHODS: An international symposium (held on 20-04-2023) gathered experts from seven HICs to (1) discuss how this paradigm shift might affect the mitigation strategies for transfusion-transmitted infections and (2) address the challenges related to gender-neutral donor selection. RESULTS: Most countries employed a similar approach for implementing a gender-neutral donor selection policy: key stakeholders were consulted; the transition was bridged by time-limited deferrals; donor compliance was monitored; and questions or remarks on anal sex and the number and/or type of sexual partners were often added. Many countries have now adopted a gender-neutral approach in which questions on pre- and post-exposure prophylaxis for human immunodeficiency virus (HIV) have been added (or retained, when already in place). Other countries used mitigation strategies, such as plasma quarantine or pathogen reduction technologies for plasma and/or platelets. CONCLUSION: The experience with gender-neutral donor selection has been largely positive among the countries covered herein and seems to be acceptable to stakeholders, donors and staff. The post-implementation surveillance data collected so far appear reassuring with regards to safety, although longer observation periods are necessary. The putative risks associated with HIV antiretrovirals should be further investigated.
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Infecções por HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Homossexualidade Masculina , Seleção de Pacientes , Infecções por HIV/epidemiologia , Doadores de Sangue , Comportamento Sexual , Seleção do DoadorRESUMO
BACKGROUND AND OBJECTIVES: As part of a large-scale project to safely increase plasma collection in Europe, the current scoping review identifies the existing evidence (gaps) on adverse events (AEs) and other health effects in plasmapheresis donors, as well as factors that may be associated with such events/effects. MATERIALS AND METHODS: We searched six databases and three registries. Study characteristics (publication type, language, study design, population, outcomes, associated factors, time of assessment, duration of follow-up, number and frequency of donations, convalescent plasma [y/n], setting and location) were synthesized narratively and in an interactive evidence gap map (EGM). RESULTS: Ninety-four research articles and five registrations were identified. Around 90% were observational studies (57 controlled and 33 uncontrolled), and most of them were performed in Europe (55%) or the United States (20%). Factors studied in association with donor health included donor characteristics (e.g., sex, age) (n = 27), cumulative number of donations (n = 21), donation frequency (n = 11), plasma collection device or programme (n = 11), donor status (first time vs. repeat) (n = 10), donation volume per session (n = 8), time in donation programme (n = 3), preventive measures (n = 2) or other (n = 9). CONCLUSION: The current scoping review provides an accessible tool for researchers and policymakers to identify the available evidence (gaps) concerning plasmapheresis donation safety. Controlled prospective studies with long-term donor follow-up are scarce. Furthermore, additional experimental studies comparing the health effects of different donation frequencies are required to inform a safe upper limit for donation frequency.
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Lacunas de Evidências , Plasmaferese , Humanos , Estudos Prospectivos , Plasmaferese/efeitos adversos , Doadores de Sangue , Europa (Continente)RESUMO
BACKGROUND AND OBJECTIVES: Pathogen reduction (PR) technology may reduce the risk of transfusion-transmitted infections (TTIs), notably transfusion-transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near-miss occurrences. MATERIALS AND METHODS: TTI and TTBI near-miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly. RESULTS: No PC-related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T-cell lymphotropic virus was reported throughout the study period. PC-mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC-mediated TTBI occurrence before PR-PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020. CONCLUSION: Transfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen-reduced PC-related TTI involving non-enveloped viruses occurs as well.
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Furocumarinas , Reação Transfusional , Humanos , Plaquetas/microbiologia , Reação Transfusional/epidemiologia , Transfusão de Sangue , Bactérias , Transfusão de Plaquetas/efeitos adversos , Raios UltravioletaRESUMO
Objective: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). Design: Open label, randomised clinical trial. Setting: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. Participants: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression. Interventions: Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40. Main outcome measures: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. Results: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). Conclusions: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. Trial registration: ClinicalTrials.gov NCT04345991.
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Importance: Red blood cell transfusion (RBCT) is frequently required in the early post-kidney transplant period, but long-term outcomes associated with RBCT is controversial. Therefore, it may be relevant to investigate the association between RBCT characteristics and transplant outcomes. Objective: To study the association between RBC storage duration and transplant outcomes. Design, Setting, and Participants: This was a nationwide retrospective cohort study based on data linking between 2 prospective French nationwide registries. Clinical transplant parameters, outcomes, and RBCT characteristics were extracted from the CRISTAL registry of the Agence de la Biomédecine and the national database of the Etablissement Français du Sang. All 12â¯559 patients having received a first kidney transplant in France between January 1, 2002, and December 31, 2008, were included. Patients were followed up from transplant to graft loss, death with a functional graft, or data retrieval in June 2016. Data were analyzed from April 2019 to June 2022. Exposures: Clinical outcomes of transplant recipients who underwent early RBCT were analyzed considering transfusion characteristics. Main Outcomes and Measures: Cox proportional hazards regression models were fitted to evaluate transplant failure defined as graft loss or death with a functional graft. Results: Among 12â¯559 patients who underwent kidney transplant, 3483 received an RBCT during the first 14 days posttransplant. The median (IQR) age of patients was 53.0 (41.5-61.2) years, and 1929 patients (55.4%) were male. Median (IQR) follow-up was 7.8 (7.6-8.0) years. In multivariable analysis, longer (vs shorter) storage duration of transfused RBC was associated with a decrease in risk of transplant failure (hazard ratio, 0.99; 95% CI, 0.98-1.00 for each additional storage day; P = .06). Patients transfused with at least 1 RBC unit stored for more than 20 days had a 5% absolute decrease in transplant failure at 3 years and 7% at 5 years compared with those who received RBC stored for less than 20 days. Conclusions and Relevance: In this study, longer RBC storage duration was associated with a decreased risk of transplant failure among patients who received kidney transplants and RBC transfusions. Preferential use of RBC with longer storage duration might improve kidney graft survival following transplant and transfusion.
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Transfusão de Eritrócitos , Transplante de Rim , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Estudos Retrospectivos , EritrócitosRESUMO
BACKGROUND AND OBJECTIVES: Data from 21 years (2000-2020) of haemovigilance were used to assess human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) incidence rates in repeat blood donors and the occurrence of transfusion-transmitted (TT) viral infections. MATERIALS AND METHODS: Blood donors who converted for HIV, HCV or HBV markers within serial three-year analysis periods were included. Epidemiological and virological data were retrieved from the national epidemiological donor database and were supplemented with information on blood components and the infection status of recipients of the previous negative donation (D.N-1) of donors who seroconverted. RESULTS: Incidence rates declined from 1.27 to 0.35/100,000 person-years for HIV, from 0.59 to 0.19 for HCV and from 1.66 to 0.18 for HBV. Risk factors and lookback for 232 HIV, 90 HCV and 74 HBV seroconversions were investigated. The main risk factor identified at post-donation interview was having sex with men (47.8% of males) for HIV and a sexual risk for HCV (30.6%) and HBV (37.1%). The viral loads and sequences were retrospectively tested in 191 HIV, 74 HCV and 62 HBV D.N-1 archived samples. Six (five HBV and one HIV-1) were positive all low viral loads. Two recipients were infected by red blood cells from two HBV seroconverting donors before the introduction of HBV-nucleic acid testing. CONCLUSION: HIV, HCV and HBV incidence rates in blood donors declined over the two past decades in France. There is a very small risk of a blood component that tests negative entering the blood supply resulting in TT infections, especially after introduction of molecular assays in donor screening.
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At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.
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Transfusão de Sangue , Plasma , Humanos , Europa (Continente) , Plasma/química , Imunoglobulinas/análiseRESUMO
BACKGROUND AND OBJECTIVES: There is a need for conversion of SARS-CoV-2 serology data from different laboratories to a harmonized international unit. We aimed to compare the performance of multiple SARS-CoV-2 antibody serology assays among 25 laboratories across 12 European countries. MATERIALS AND METHODS: To investigate this we have distributed to all participating laboratories a panel of 15 SARS-CoV-2 plasma samples and a single batch of pooled plasma calibrated to the WHO IS 20/136 standard. RESULTS: All assays showed excellent discrimination between SARS-CoV-2 seronegative plasma samples and pre-vaccinated seropositive plasma samples but differed substantially in raw antibody titres. Titres could be harmonized to binding antibody units per millilitre by calibration in relation to a reference reagent. CONCLUSION: The standardization of antibody quantification is of paramount importance to allow interpretation and comparison of serology data reported in clinical trials in order to identify donor cohorts from whom the most effective convalescent plasma can be collected.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Laboratórios , Soroterapia para COVID-19 , Europa (Continente) , Anticorpos Antivirais , Teste para COVID-19RESUMO
BACKGROUND AND OBJECTIVES: Since the advent of AIDS, men who have sex with men (MSM) have often been deferred from blood donation. In France, quarantine plasma donation by MSM donors with the same deferral rules as for other donors was introduced in July 2016 and continued up to March 2022. At this time, MSM-specific deferral criteria were lifted for all blood or plasma donation. The donor deferral, as well as rate of infectious markers in plasma donors who would have been otherwise deferred for MSM activity, was evaluated and compared with those of the other donors during the same time period from June 2016 to March 2022. RESULTS: A total of 8843 MSM donors made 12,250 plasma donation applications. The overall deferral rate was very high (75.2%), mainly due to the absence of apheresis capacity at the donation site. The deferral criteria for sexual risk were present in 12.1% of MSM donors compared with 1.0% in other plasma and blood donors (p < 0.001). Overall, 994 MSM donors made 2880 plasma donations. Of these, one donation was HIV positive (34.7 vs. 0.6/105 donations by other donors, relative risk [RR]: 61.0 [95% confidence interval [CI]: 8.5-437.7]), one was HBV positive (34.7 vs. 4.5/105 , RR: 7.7 [95% CI: 1.1-54.6]) and none were HCV positive (0 vs. 2.4/105 ). Additionally, 21 donations were syphilis positive (729.2 vs. 10.7/105 , RR: 67.9 [95% CI: 44.2-104.4]). A post hoc analysis of eligible MSM donors who were unable to donate plasma due to logistic constraints yielded similar findings. CONCLUSION: Plasma donation by donors who would have been otherwise deferred for MSM activity was associated with both an increased deferral rate for sexual risk and an increased rate of infectious markers, notably syphilis.
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Doação de Sangue , Doadores de Sangue , Homossexualidade Masculina , Humanos , Masculino , França , Minorias Sexuais e de GêneroRESUMO
INTRODUCTION: COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. METHODS AND ANALYSIS: COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. ETHICS AND DISSEMINATION: Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. TRIAL REGISTRATION: Clinical Trials.gov (NCT05271929), EudraCT (2021-006621-22).