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

Vasiliki Pappa, Anthi Bouchla, Evangelos Terpos, Thomas P Thomopoulos, Margherita Rosati, Dimitris Stellas, Anastasia Antoniadou, Andreas Mentis, Sotirios G Papageorgiou, Marianna Politou, Anastasia Kotanidou, Ioannis Kalomenidis, Garyfalia Poulakou, Edison Jahaj, Eleni Korompoki, Sotiria Grigoropoulou, Xintao Hu, Jenifer Bear, Sevasti Karaliota, Robert Burns, Maria Pagoni, Ioannis Trontzas, Elisavet Grouzi, Stavroula Labropoulou, Kostantinos Stamoulis, Aristotelis Bamias, Sotirios Tsiodras, Barbara K Felber, George N Pavlakis, Meletios- Athanasios Dimopoulos, Vasiliki Pappa, Anthi Bouchla, Evangelos Terpos, Thomas P Thomopoulos, Margherita Rosati, Dimitris Stellas, Anastasia Antoniadou, Andreas Mentis, Sotirios G Papageorgiou, Marianna Politou, Anastasia Kotanidou, Ioannis Kalomenidis, Garyfalia Poulakou, Edison Jahaj, Eleni Korompoki, Sotiria Grigoropoulou, Xintao Hu, Jenifer Bear, Sevasti Karaliota, Robert Burns, Maria Pagoni, Ioannis Trontzas, Elisavet Grouzi, Stavroula Labropoulou, Kostantinos Stamoulis, Aristotelis Bamias, Sotirios Tsiodras, Barbara K Felber, George N Pavlakis, Meletios- Athanasios Dimopoulos

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).

Keywords: COVID-19; SARS-CoV-2 antibodies; convalescent plasma; efficacy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier Survival analysis of the recipients and controls.
Figure 2
Figure 2
(a) Trend of anti-S1 IgG and IgA antibody levels in the recipients following CP infusion. (b) Trends of Nucleocapsid and N_RBD in the recipients following CP Infusion. (c) Trend of Spike, Spike_RBD and Nab in the recipients following CP infusion. (d) Probability of detection of anti-S1 IgG and IgA in the recipients at day 1 of CP infusion post symptom onset.
Figure 3
Figure 3
Trend of antibodies by baseline antibody level: (a) anti-S1 IgG, (b) anti-S1-IgA, (c) Nucleocapsid, (d) N_RBD, (e) Spike, (f) Spike_RBD, (g) neutralizing antibodies (ID50).

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