Joyner 2020.

Study characteristics
Methods	Trial design: expanded access Type of publication: preprint publication Setting: hospital, 66% ICU Recruitment dates: 13 April‐11 May 2020 Country: USA Language: English Number of centres: 12 Trial registration number: NCT04338360 Date of trial registration: 08 April 2020
Participants	Age: median age 62 years (18‐97 years) Gender: 3153 men, 1824 women and 23 people in other gender/sex categories Ethnicity: Asian (6%), American Indian or Alaskan Native (< 1%), black (18%), white (49%), Native Hawaiian or Pacific Islander (< 1%) and multi‐racial (< 1%) Number of participants (recruited/allocated/evaluated): recruited: 14,288 patients; allocated: 8932 patients; evaluated: the first 5000 patients Severity of disease: hospitalised adults with severe or life‐threatening COVID‐19 At the time of enrolment, 4051 (81%) patients had severe or life‐threatening COVID‐19 72% had respiratory failure 63% reported dyspnoea 62% had a blood oxygen saturation ≤ 93% 43% had lung infiltrates > 50% within 24‐28 h of enrolment 38% had a respiratory frequency ≥ 30 breaths/min‐1 34% had partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300 18% had multiple organ dysfunction or failure 15% had septic shock 949 (19%) were judged to have a high risk of progressing to severe or life‐threatening COVID‐19 Prior to CP transfusion, 3316 patients (66%) were admitted to the ICU Co‐morbidities: NR Inclusion criteria: Age ≥ 18 years Laboratory‐confirmed diagnosis of infection with SARS‐CoV‐2 Admitted to an acute care facility for the treatment of COVID‐19 complications Severe or life‐threatening COVID‐19, or judged by the treating provider to be at high risk of progression to severe or life‐threatening disease. (Severe COVID‐19 is defined by one or more of the following: dyspnoea, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, PaO2/FiO2 < 300, lung infiltrates > 50% within 24‐48 h. Life‐threatening COVID‐19 is defined as one or more of the following: multiple organ dysfunction or failure, septic shock, respiratory failure.) Informed consent provided by the patient or healthcare proxy Exclusion criteria: NR Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): NR
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP therapy Details of CP: Type of plasma: ABO‐compatible COVID‐19 CP Volume:  200‐500 mL; according to institutional transfusion guidelines Number of doses: 1 Type of antibody test(s) and antibody‐titre(s): NR Pathogen inactivated or not: NR RT‐PCR tested: NR Details of donors:  Gender:  NR HLA and HNA antibody‐negative: NR Severity of disease: NR Timing from recovery from disease: NR RT‐PCR tested: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): NR Comparator: none Concomitant therapy: NR Duration of follow‐up: 4‐h follow‐up for SAEs, 7‐day follow‐up for mortality Treatment cross‐overs: not applicable Compliance with assigned treatment: NR
Outcomes	Primary study outcome(s): key safety metrics after transfusion of ABO‐compatible human COVID‐19 CP Primary review outcomes All‐cause mortality at hospital discharge: 7‐day mortality rate Time to death: NR Secondary review outcomes Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): serious transfusion‐related AEs reported Number of participants with SAEs: reported; 4h observation period Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: NR 30‐day and 90‐day mortality: NR Admission on the ICU: NR Length of stay on the ICU: NR Time to discharge from hospital: NR QoL: NR Additional study outcomes: none
Notes	Sponsor/funding: US Department of Health and Human Services (HHS), Biomedical Advanced Research and Development Authority (BARDA) grant 75A50120C00096 (to MJJ), National Center for Advancing Translational Sciences (NCATS) grant UL1TR002377, National Heart, Lung, and Blood Institute (NHLBI) grant 5R35HL139854 (to MJJ), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5T32DK07352 (to JWS and CCW), Natural Sciences and Engineering Research Council of Canada (NSERC) PDF‐532926‐2019 (to SAK), National Institute of Allergy and Infectious Disease (NIAID) grants R21 AI145356 and R21 AI152318 (to DF), R01 AI152078 9 (to AC), National Heart Lung and Blood Institute RO1 HL059842 (to AC), Schwab Charitable Fund (Eric E Schmidt, Wendy Schmidt donors), United Health Group, National Basketball Association (NBA), Millennium Pharmaceuticals, Octopharma USA, Inc, and the Mayo Clinic COIs: NR Other: preliminary analysis, study still ongoing