Shen 2020.

Study characteristics
Methods	Trial design: case series  Type of publication: preliminary communication in JAMA  Setting: hospital, infectious disease department Recruitment dates: 20 January 2020‐25 March 2020 Country: China Language: English Number of centres: 1 Trial registration number: NR Date of registration: NR
Participants	Age: 36‐65 years Gender: 3 male, 2 female Ethnicity: NR  Number of participants (recruited/allocated/evaluated): 5 Severity of disease: critical  Comorbidities: hypertension, mitral insufficiency (1 participant), none in 4 participants  Inclusion criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; PAO2/FIO2 < 300; and mechanical ventilation Exclusion criteria: NR Additional diagnoses: bacterial pneumonia; fungal pneumonia; severe ARDS; myocardial damage, MODS Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): antiviral therapy (including lopinavir/ritonavir; interferon alfa‐1b; favipiravir, arbidol; darunavir), corticosteroids (methylprednisolone), mechanical ventilation
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP  Details of CP: Type of plasma: CP prepared from 5 donors aged 18‐60 years by apheresis Volume: 400 mL total of ABO‐compatible CP on the same day it was obtained from the donor Number of doses: 2 (each dose 200‐250 mL) on the same day  Antibody test and antibody‐titre: SARS‐CoV‐2–specific antibody (IgG) binding titre > 1:1000 (end point dilution titre, by ELISA) and a neutralisation titre > 40 (end point dilution titre); horseradish peroxidase–conjugated goat anti–human IgG (for IgG antibody titre detection) and IgM (for IgM antibody titre detection) (Sangon Biotech) Pathogen inactivated or not: NR RT‐PCR tested: NR Details of donors:  Gender: NR HLA and HNA antibody‐negative: NR Severity of disease: all donors had been previously diagnosed with laboratory‐confirmed COVID‐19 and subsequently tested negative for SARS‐CoV‐2 and other respiratory viruses, as well as for hepatitis B virus, hepatitis C virus, HIV, and syphilis at the time of blood donation Timing from recovery from disease: the donors had been well (asymptomatic) for at least 10 days RT‐PCR tested: a serum SARS‐CoV‐2– specific ELISA antibody titre > 1:1000 and a neutralising antibody titre > 40 Treatment details, including time of plasma therapy (e.g. early stage of disease): administered between 10 and 22 days after admission For studies including a control group: comparator (type): not applicable  Concomitant therapy: antiviral therapy (including lopinavir/ritonavir; interferon alfa‐1b; favipiravir, arbidol; darunavir), corticosteroids (methylprednisolone) Duration of follow‐up: up to 63 days from hospital admission Treatment cross‐overs: none Compliance with assigned treatment: good (all compliant)
Outcomes	Primary study outcome: initial clinical experience with CP transfusion administered to critically ill patients with COVID‐19 Primary review outcomes All‐cause mortality at hospital discharge: reported Time to death: not applicable 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): NR Number of participants with SAEs: NR Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: 3 discharged from hospital, 2 remained in hospital (stable) 30‐day and 90‐day mortality: NR (all alive)   Admission on the ICU: all were admitted to ICU  Length of stay on the ICU: 11, 14, 18 days for 3 participants, remained in ICU for 2 participants  Time to discharge from hospital: 51‐55 days (3 participants), 2 remained in hospital (stable) Additional study outcomes: changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0‐24, with higher scores indicating more severe illness), PAO2/FIO2, viral load (qRT‐PCR), serum antibody titre (ELISA), routine blood biochemical index (CRP, procalcitonin, IL6), ARDS, and ventilatory and ECMO supports before and after CP transfusion, CT chest findings
Notes	Sponsor/funding: "this work was supported by the National Science and Technology Major Project (2018ZX10711001, 2017ZX10103011, 2017ZX10204401), Sanming Project of Medicine in Shenzhen (SZSM201412003, SZSM201512005), China Postdoctoral Science Foundation (2019T120147, 2018M641508), Shenzhen Science and Technology Research and Development Project (202002073000001), National Natural Science Foundation of China (81902058), Shenzhen Science and Technology Research and Development Project (202002073000002), and The Key Technology R&D Program of Tianjin (17YFZCSY01090)." COIs: no conflicts to disclose Other:" the study was approved by the ethics committees from Shenzhen Third People’s Hospital, and each participant gave written informed consent."