Abstract: RESEARCH High-Dose Convalescent Plasma for Treatment of Severe COVID-19 Gil C. De Santis, Luciana Correa Oliveira, Pedro M.M. Garibaldi, Carlos E.L. Almado, Julio Croda, Ghislaine G.A. Arcanjo, Érika A.F. Oliveira, Adriana C. Tonacio, Dante M. Langhi Jr., José O. Bordin, Renato N. Gilio, Leonardo C. Palma, Elaine V. Santos, Simone K. Haddad, Benedito P.A. Prado Jr., Marjorie Cornejo Pontelli, Rogério Gomes, Carlos H. Miranda, Maria Auxiliadora Martins, Dimas T. Covas, Eurico Arruda, Benedito A.L. Fonseca, Rodrigo T. Calado To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19. Author affiliations: University of São Paulo, São Paulo, Brazil (G.C. De Santis, L.C. Oliveira, E.V. Santos, S.K. Haddad, B.P.A. Prado Jr., D.T. Covas, R.T. Calado); Hospital Estadual de Serrana, Serrana, Brazil (P.M.M. Garibaldi, C.E.L. Almado); Hospital Regional do Mato Grosso do Sul, Campo Grande, Brazil (J. Croda); Fundação Oswaldo Cruz, Campo Grande (J. Croda); Universidade do Mato Grosso do Sul, Campo Grande (J. Croda, G.G.A. Arcanjo); Hospital São Camilo, São Paulo (É.A.F. Oliveira, A.C. Tonacio, D.M. Langhi Jr.); Universidade Federal de São Paulo, São Paulo (D.M. Langhi Jr., J.O. Bordin); Hospital Estadual de Américo Brasiliense, Américo Brasiliense, Brazil (R.N. Gilio); Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil (L.C. Palma); Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, São Paulo (M.C. Pontelli, R. Gomes, C.H. Miranda, M.A. Martins, E. Arruda, B.A.L. Fonseca) DOI: https://doi.org/10.3201/eid2803.212299 548 C linical signs and symptoms of coronavirus disease (COVID-19) are pleomorphic, varying from none (asymptomatic) to life-threatening. Typical signs/ symptoms are fever, dry cough, dyspnea, fatigue, myalgia, anosmia, and ageusia (1). Radiography or computed tomography of the chest usually reveals bilateral pulmonary ground-glass opacifications, mainly in posterior and peripheral areas of the lungs (2). The most common laboratory test alterations are lymphopenia and elevated serum concentrations of inflammatory biomarkers and D-dimers (3). Risk factors for unfavorable outcomes are older age, concurrent conditions, and perhaps but of lesser importance, blood type A (4,5). Thus far, there is no consensual agreement about specific therapy for this disease, despite several attempts to develop one (3,6). More recently, antiviral agents such as MK-4482/EIDD-2801 and PF-07321332 seem to be promising (7,8). In the past, passive antibody transfer by plasma or serum..