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).

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

“…Our results are in line with a recent study that found no difference in viral clearance rate between CP and standard of care in critically ill patients [ 16 ]. Furthermore, Kurtz et al found that only 46% of life-threatening COVID-19 patients had negative SARS-CoV-2 PCR tests on day 14 after CP administration, which is in agreement with our findings (40.6% on day 14) [ 15 ]. Therefore, the incapability of CP treatment to increase the viral clearance might be due to the severity of COVID-19 patients, which may have prevented any potential benefit of CP.…”

“…Our results are of clinical importance and add significant data to CP’s existing literature in life-threatening COVID-19 patients. CP was, on average, given relatively early after symptoms onset in a rapidly deteriorating disease process, further distinguishing this group from the other studies [ 13 , 15 , 16 ]. We used robust statistical tools to account for confounding variables and minimize other treatment effects.…”

“…A very few studies focused on critically ill COVID-19 patients in ICU requiring HFNO and/or mechanical ventilation [ 15 , 16 ]. Kurtz et al, in a retrospective study of 113 life-threatening COVID-19 patients with acute respiratory failure (86% received mechanical ventilation) in ICU, found no association between CP administration and clinical improvement or death compared to standard of care management [ 15 ]. Additionally, no difference in respiratory improvement between CP treatment and standard of care was found in another retrospective study that included 80 critically ill COVID-19 patients, of whom 86% required IMV [ 16 ].…”

“…Additionally, no difference in respiratory improvement between CP treatment and standard of care was found in another retrospective study that included 80 critically ill COVID-19 patients, of whom 86% required IMV [ 16 ]. However, no information about the antibody titer levels in the infused CP was provided in the two studies; additionally, the duration from symptoms’ onset to CP administration was long (median 13 days and 10 days, respectively) [ 15 , 16 ]. In a randomized, open-label clinical trial of CP treatment in 103 patients with severe or life-threatening COVID-19 pneumonia, Li et al found no differences in the time to clinical improvement or 28-day mortality in comparison with placebo [ 13 ].…”

“…These trials included few or no patients with life-threatening COVID-19 disease requiring high flow oxygen therapy (HFNO), non-invasive ventilation (NIV), or invasive mechanical ventilation (IMV). Data focusing on the critically ill COVID-19 patients in the intensive care unit (ICU) are still scarce [ 15 , 16 ]. Thus, the benefits of CP in these patients are still not known.…”