Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

Establishment of reference intervals and transfusion criterion for Sonoclot analysis.

Sonoclot analyzer has been widely used in many countries. But the reference intervals provided by the manufacturer were derived from only 45 participants, and there was no cut-off value for transfusion for Sonoclot analysis. This study aimed to establish reference intervals and transfusion criterion for Sonoclot analysis. Volunteers were recruited from healthy Chinese adults and patients undergoing cardiac surgery. Blood samples were withdrawn from forearm vein and measured for activated clotting time (ACT), clot rate (CR), platelet function (PF), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), and platelet count (PLT). The reference intervals were determined by the nonparametric method. Cut-off values were determined by the receiver operating characteristics curve. A total of 135 healthy volunteers and 281 patients were enrolled. The 95% reference intervals were 96-195 s, 22-51 signal U/min, >1.6 for ACT, CR, PF respectively. In the 281 patients, the results of APTT, FIB, PLT, ACT, CR, and PF ranged from 20.5-300.0 s, 0.28-4.11 g/L, (19.0-387.3)×109/L, 80-514 s, 2.9-74 signal U/min, and 0.1-5.1 respectively. The cut-off values for transfusion were >208, ≤14, and ≤1.3 for ACT, CR, PF respectively. The cut-off values of Sonoclot analysis were within the manufacturer's reference intervals, while they were outside the reference intervals established in this study. The results suggested that the manufacturer's reference intervals were not suitable for Chinese. The reference intervals and cut-off values established in this study will be helpful to Chinese patients.