A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis

Abstract

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

“…From 7 May 2020 to 10 November 2020, 60 patients with WHO grade ≥4 COVID-19 disease were enrolled and received CP transfusion, and the clinical characteristics and outcomes of these patients have been previously described [ 20 ]. Among them, 31 patients had at least three consecutive ELISA antibody measurements and viral load data and were included in the current analysis.…”

“…All patients provided written informed consent. Details regarding the study protocol, including the inclusion and exclusion criteria, have been described elsewhere [ 20 ]. In short, following informed consent, patients with severe COVID-19 received single-donor CP, divided into three equal doses and infused on days 1, 3, and 5.…”

“…A real-time one-step reverse transcription PCR (RT-PCR), specific for the ORF1ab gene of SARS-CoV-2 and the N gene of all other coronaviruses, was performed using the VIASURE SARS-CoV-2 Real Time PCR Detection Kit (CerTest Biotec SL, Zaragoza, Spain) as detailed elsewhere [ 20 ]. Briefly, nasopharyngeal swabs collected on days 1, 4, 7, 10, 14, 21, and 28 were analyzed.…”

“…On the other hand, individual randomized control trials on the efficacy of convalescent plasma (CP) have shown negative results [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]; however, two recent meta-analyses have demonstrated the efficacy of convalescent plasma (CP) in mortality reduction of patients with severe COVID-19, similarly to the results of several matched-control trials [ 18 , 19 ]. A survival benefit of patients treated with CP was recently shown by our group in a matched propensity score analysis of 59 patients [ 20 ].…”

The Effectiveness of Convalescent Plasma for the Treatment of Novel Corona Virus Disease 2019: A Systematic Review and Meta-Analysis

“…Many researches have been suggested that CCP can make a positive difference in the treatment of COVID-19 infection (10)(11)(12)(13). However, more and more randomized controlled trials (RCTs) have been finished recently and failed to prove the survival benefit and clinical improvement with CCP, compared with the control group (14)(15)(16).…”