Duan 2020.

Study characteristics
Methods	Trial design: prospective single‐arm pilot study Type of publication: journal publication Setting: inpatient Recruitment dates:  23 January 2020‐19 February 2020 Country: China Language: English Number of centres: 3 Trial registration number: ChiCTR2000030046 Date of trial registration: 21 February 2020
Participants	Age: median age 52.5 years (IQR 45.0‐59.5 years) Gender: 6 male, 4 female Ethnicity: NR Number of participants (recruited/allocated/evaluated): 10 Severity of disease: severe Co‐morbiditities: cardiovascular and/or cerebrovascular diseases and essential hypertension Inclusion criteria: 1 of the conditions 2‐4 plus condition 1: 1) age ≥ 18 years; 2) respiratory distress, respiratory rate ≥ 30 breaths/min; 3) oxygen saturation level < 93% in resting state; and 4) PaO2/FiO2 ≤ 300 mmHg (1 mmHg = 0.133 kPa) Exclusion criteria: 1) previous allergic history to plasma or ingredients (sodium citrate); 2) cases with serious general conditions, such as severe organ dysfunction, who were not suitable for CP transfusion Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): oxygen support (9/10 before CP therapy, 8/10 after CP therapy): mechanical ventilation, high‐flow nasal cannula oxygenation, conventional low‐flow nasal cannula oxygenation antiviral treatments (10/10): arbidol 0.2 g every 8 h) by mouth, monotherapy or combination therapy with remdesivir 0.2 g/day IV or ribavirin 0.5 g/day IV or peramivir 0.3 g/day IV, or ribavirin 0.5 g/day IV monotherapy, IFN‐ɑ 500 MIU/day inhalation, oseltamivir 75 mg every 12 h by mouth, peramivir 0.3 g/day IV antibacterial or antifungal treatment (8/10): when participants had coinfection corticosteroids 6/10): IV methylprednisolone (20 mg every 24 h)
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP therapy Details of CP: Type of plasma: apheresis plasma. Apheresis was performed using a Baxter CS 300 cell separator (Baxter).  A 200‐ to 400‐mL ABO‐compatible plasma sample was harvested from each donor depending on age and body weight, and each sample was divided and stored as 200 mL aliquots at 4 °C without any detergent or heat treatment. The CP was then treated with methylene blue and light treatment for 30 min in the medical plasma virus inactivation cabinet (Shandong Zhongbaokang Medical Appliance Co, Ltd) Volume: 200 mL Number of doses: 1 Type of antibody test(s) and antibody‐titre(s): the neutralising activity against SARS‐CoV‐2 was evaluated by classical plaque reduction test using a recently isolated viral strain. Antibody titre: > 1:160 Pathogen inactivated or not: methylene blue photochemistry RT‐PCR tested: NR Details of donors: CP for treatment was collected from 40 donors. The median age was 42.0 years (IQR 32.5‐49 years). 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): administered between 10 and 20 days after admission (median: 16.5 days) For studies including a control group: comparator (type): historic control, matched by age, gender and severity of disease Concomitant therapy: mechanical ventilation, high‐flow nasal cannula oxygenation, conventional low‐flow nasal cannula oxygenation, arbidol 0.2 g every 8 h by mouth, monotherapy or combination therapy with remdesivir 0.2 g/day IV or ribavirin 0.5 g/day IV or peramivir 0.3 g/day IV, or ribavirin 0.5 g/day IV monotherapy, IFN‐ɑ 500 MIU/day inhalation, oseltamivir 75 mg every 12 h by mouth, peramivir 0.3 g/day IV, antibacterial or antifungal treatment when participants had coinfection, IV methylprednisolone (20 mg every 24 h) Duration of follow‐up: NR Treatment cross‐overs: not applicable Compliance with assigned treatment: good (all compliant)
Outcomes	Primary study outcome The changes of clinical symptom, laboratory and radiological data 3 days after CP transfusion Primary review outcomes All‐cause mortality at hospital discharge: NR 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): only CP transfusion‐related AEs reported (evanescent facial red spot) Number of participants with SAEs: reported, none occurred Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: reported; up to day 4 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: lymphocyte count, CRP, ALT, AST, total bilirubin, SaO2, clinical symptoms improvement, clinical outcome, defined as: death, stable, improved, discharged, neutralising antibody titres, SARS‐CoV‐2 RNA by RT‐PCR, reduction of pulmonary lesions on chest CT
Notes	Sponsor/funding: this study was funded by Key projects of the Ministry of Science and Technology China 'Preparation of specific plasma and specific globulin from patients with a recovery period of COVID‐19 infection' (Project 2020YFC0841800). This work was also supported by Shanghai Guangci Translational Medicine Development Foundation. We thank all patients and donors involved in this study. COIs: study authors declare no competing interests Other: "written informed consent according to the Declaration of Helsinki was obtained from each patient or legal relatives. This study was approved by the Ethics Committee of the China National Biotec Group Co., Ltd. (Approval number 2020‐0001)."