Liu 2020.

Study characteristics
Methods	Trial design: matched control study  Type of publication: preprint Setting: hospitalised patients Recruitment dates: 24 March 2020‐8 April 2020 Country: USA Language: English Number of centres: 1 Trial registration number: NR Date of trial registration: NR
Participants	Age: 55 (± 13) years Gender:  2/3rd male, 1/3rd female Ethnicity: NR Number of participants (recruited/allocated/evaluated): 45 recruited, 39 allocated and evaluated (matched retrospectively to controls) Severity of disease: severe or life‐threatening disease and consented to therapy Co‐morbidities: 21 (54%) obese, 7 (18%) current or former history of tobacco use, 1 (3%) participant had end‐stage renal disease requiring peritoneal dialysis, asthma in 3 (8%), cancer in 2 (5%), COPD in 1 (3%), diabetes in 8 (21%), OSA in 2 (5%) Inclusion criteria: severe or life‐threatening disease and consented to therapy Exclusion criteria: NR improvement of disease (4 of the 45 recruited patients did not receive plasma transfusion because they improved) Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): azithromycin, broad‐spectrum antibiotics, hydroxychloroquine, therapeutic anticoagulants, corticosteroids, directly acting antivirals, stem cells, and interleukin 1 and interleukin 6 inhibitors
Interventions	Intervention(s): CP therapy Details of CP: Type of plasma: plasmapheresis ABO‐matched   Volume:  250 mL each dose (500 mL total) Number of doses: 2, each unit infused over 1 to 2 h Type of antibody test(s) and antibody‐titre(s): 2‐step Spike protein‐directed ELISA, anti‐spike antibody titre of ≥ 1:320 dilution Pathogen inactivated: 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): severe to life‐threatening disease, median time between admission and transfusion was 4 (1 to 7) days Comparator: propensity‐score matched cohort from the same hospital and calendar period matching was performed on the following variables: administration of hydroxychloroquine and azithromycin, intubation status and duration, length of hospital stay, oxygen requirement on the day of transfusion; control patients were matched to plasma recipients by length of stay prior to transfusion Concomitant therapy: azithromycin, broad‐spectrum antibiotics, hydroxychloroquine, therapeutic anticoagulants, corticosteroids, directly acting antivirals, stem cells, and interleukin 1 and interleukin 6 inhibitors, oxygen therapy (87%), mechanical ventilation (10%), 69.2% were receiving high‐flow oxygen  Duration of follow‐up: median follow‐up time was 11 (1 to 28) days for the plasma group and 9 (0 to 31) 186 days for the control group Treatment cross‐overs: not applicable Compliance with assigned treatment: good (all compliant)
Outcomes	Primary study outcome(s): supplemental oxygen requirements Primary review outcomes All‐cause mortality at hospital discharge: reported (survival at 3 time points: days 1, 7, and 14 post‐transfusion) Time to death: reported  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): reported; assessed every 15 minutes after transfusion Number of participants with SAEs: reported Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: reported (supplemental oxygen requirements three time points: days 1, 7, and 14 post‐transfusion) 30‐day and 90‐day mortality:  NR (survival at 3 time points: days 1, 7, and 14 post‐transfusion) Admission on the ICU: reported Length of stay on the ICU: reported Time to discharge from hospital: reported QoL: NR Additional study outcomes: none
Notes	Sponsor/funding: Dr. Krammer reports that patent applications have been filed for the assay used to select plasma donors, and Mount Sinai has licensed its use to several companies. Dr. Aberg reports grants and personal fees from Gilead, grants and personal fees from Merck, grants and personal fees from Janssen, personal fees from Theratech, personal fees from Medicure, grants from Regeneron, grants and personal fees from Viiv, outside the submitted work. No external funding COIs: all other study authors have nothing to disclose Other: all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.