Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study

Abstract

Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19. Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan-Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed. Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48-68), disease duration was 10 days (IQR 6-13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49-1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52-1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP. Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease. Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).

Keywords: COVID-19; acute respiratory distress syndrome; convalescent plasma; coronavirus; survival.

Figure 1

Univariable survival curves (Kaplan–Meier) of 28-day outcomes: Probability of clinical improvement (A) and survival (B) in Standard of Care (SOC) and Convalescent Plasma (CP) groups. Differences among curves were assessed using the log-rank test with a confidence level of 0.05.

Figure 2

Univariable survival curves (Kaplan–Meier) of 28-day outcomes: Probability of clinical improvement (A) and survival (B) in Standard of Care (SOC), 1 infusion of Convalescent Plasma (CP) and 2 infusions of CP groups. Differences among curves were assessed using the log-rank test with a confidence level of 0.05.

Figure 3

Clinical status and respiratory support on day 14 after admission, according to admission status. Columns represent patients in the Convalescent Plasma and Standard of Care groups, separated by their intubated and non-intubated status at admission to the ICU. Colors represent percentages and numbers within colors represent the N of patients in each subgroup.

Figure 4

Temporal changes of clinical and laboratory parameters in patients that received convalescent plasma and propensity-matched controls. Data are expressed as mean (standard error of the mean). *corresponds to p < 0.05. BL, baseline; SOFA, sequential organ failure assessment; Delta values represent the change from baseline. (A) C reactive protein. (B) Delta lymphocytes. (C) Delta SOFA score. (D) PaO2/FiO2 ratio.