Bajpai 2020.

Study characteristics
Methods	Trial design: RCT, open label Type of publication: preprint publication Setting: hospital (inpatient and ICU) Recruitment dates: 21 April 2020 until final follow‐up on 30 May 2020 Country: India Language: English Number of centres: 1 Trial registration number: NCT04346446 Date of trial registration: 15 April 2020
Participants	Age: mean 48.2 ± 9.8 Sex: 75.9% of males in the intervention and control group together Ethnicity: NR Number of participants (recruited/allocated/evaluated): 51/31/29 Severity of condition according to study definition: severe (respiratory rate (RR) ≥ 30/min, oxygen saturation level less than 93% in resting state, the partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg, lung infiltrates > 50% within 24 to 48 h) Severity of condition according to WHO score: level 5‐7 Comorbidities: BMI Inclusion criteria Written informed consent SARS‐CoV‐2 infection (positive by real‐time PCR assay) patient Severe COVID‐19 (respiratory rate (RR) ≥ 30/min, oxygen saturation level less than 93% in resting state, the partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤300 mmHg, lung infiltrates > 50% within 24 to 48 h) Exclusion criteria Failure to obtain informed consent Patients less than 18 years or more than 65 years of age Those with co‐morbid conditions (cardiopulmonary disease‐structural or valvular heart disease, coronary artery disease, COPD, chronic liver disease, chronic kidney disease) Patients presenting with multi‐organ failure or on mechanical ventilation Pregnant females Individuals with HIV Viral hepatitis, cancer, morbid obesity with a BMI > 35 kg/m2 Extremely moribund patients with an expected life expectancy of < 24 h, Haemodynamic instability requiring vasopressors Previously known history of allergy to plasma, or a PaO2/FiO2 ratio less than 150 Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation) Donor eligibility criteria From COVID‐19 recovered patients after 14 days of complete resolution of symptoms by plasmaphaeresis Two consecutive test negative results (RT‐PCR) 24 h apart Due consent Medical history, physical examination and laboratory tests Donor exclusion criteria: NR
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP Details of CP Type of plasma: COPLA convalescent plasma transfusion (ABO blood group compatible plasma) Volume:  500 mL (either convalescent or FFP) Number of doses: 2 divided doses on consecutive days Type of antibody test and antibody‐titre: the titre was determined by ELISA (SARS‐CoV‐2 Spike S1‐RBD IgG Detection Kit, Genscript, USA) using positive, negative controls and sample dilutions (1:80, 1:160, 1:320, 1:640 and 1:1000). The S1 RBD IgG titre of 1:80 or above was preferred. Pathogen inactivated or not: NR RT‐PCR tested: yes Details of donors Sex: 14 male, 0 female HLA and HNA antibody‐negative: NR Severity of disease: NR Timing from recovery from disease: 14 days of complete resolution of symptoms RT‐PCR tested: yes Treatment details, including time of plasma therapy (e.g. early stage of disease): transfusion within three days of onset of symptoms of severe COVID‐19 For studies including a control group: comparator (type): fresh frozen plasma (FFP) Concomitant therapy: standard care Medically, all patients received a course of Hydroxychloroquine 400 mg (twice daily) on day 1, followed by 200 mg (twice daily) for five days along with oral azithromycin 500 mg (once daily) for five days. Standard medications for the control of diabetes and hypertension were given when required. Duration of follow‐up: between 21 April and 30 May 2020 Treatment cross‐overs: no Compliance with assigned treatment: yes
Outcomes	Primary study outcome Proportion of participants remaining free of mechanical ventilation (Day 7) Primary review outcomes All‐cause mortality at hospital discharge: NR 30‐day mortality: yes (mortality at day 28) 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): any AEs reported Number of participants with SAEs: NR Clinical status, assessed by need for respiratory support with standardised scales (e.g. WHO Clinical Progression Scale (WHO 2020e), WHO Ordinal Scale for Clinical Improvement (WHO 2020f)) at up to 7 days, 8 to 15 days, 16 to 30 days: NR Mortality (time to event): NR 90‐day mortality: NR Time to discharge from hospital: yes (duration of hospital stay) Admission on the ICU: NR Length of stay on the ICU: yes Viral clearance, assessed with reverse transcription polymerase chain reaction (RT‐PCR) test for SARS‐CoV‐2 at baseline, up to 3, 7, and 15 days: NR QoL: NR Additional review outcomes Improvement in Pa02/Fi02 ratio (day 2, day 7) SOFA scores reduction (day 2, day 7) Requirements of Vasopressor (day 28) Days free of dialysis (day 28) Clinical assessment of patients was done by assessing reduction in respiratory rate, and improvement in oxygen saturation (day 2 and day 7) Laboratory effects of plasma therapy by improvement in lymphocyte count Ct value (day 7) Any adverse transfusion events with plasma transfusion
Notes	Preprint published: 27 October 2020 Sponsor/funding: Institute of Liver and Biliary Sciences, India