Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study

Abstract

Background Convalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal. Methods In this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection. CPT was administered to patients with severe to life-threatening infections who were at high risk for progression or clinical worsening despite REM. Clinical findings and outcomes were recorded until discharge or death. Results Patients were classified as having moderate (24.2%), severe (64%), or life-threatening (11.7%) COVID-19 infection. The majority of CPT and CPT + REM recipients had severe to life-threatening infections (CPT 98.3%; CPT + REM 92.1%) and were admitted to the intensive care unit (ICU; CPT 91.8%; CPT + REM 94.6%) compared with those who received REM alone (73.3% and 57.5%, respectively). Of 1083 patients with reported outcomes, 78.4% were discharged and 21.6% died. The discharge rate was 84% for REM (n = 910), 39% for CPT (n = 59), and 54.4% for CPT + REM (n = 114) recipients. In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for recipients of remdesivir alone (0.82; 95% CI, 0.79–0.84) compared with CPT (0.58; 95% CI, 0.47–0.70) and CPT + REM (0.67; 95% CI, 0.60–0.74) recipients. Adverse events of remdesivir and CPT were reported in <5% of patients. Conclusions This study demonstrates a safe rollout of CPT and REM in a resource-limited setting. Remdesivir recipients had less severe infection and better outcomes. ClinicalTrials.gov identifier. NCT04570982.

Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies

“…The overall clinical improvement observed after CP therapy correlated strongly with early administration, as demonstrated by the rapid decrease in oxygen demand and length of hospital stay. The decreasing effectiveness of plasma therapy late in the course of the disease or even after remdesivir therapy has been also emphasized by a recent large-scale study [25]. Our observation is consistent with previously published reports regarding the discrepancy between the time needed for clinical recovery and PCR negativity.…”

Safety and Efficacy of Convalescent Plasma Combined with Other Pharmaceutical Agents for Treatment of COVID-19 in Hospitalized Patients: A Systematic Review and Meta-Analysis

“…The screening of the full text of such articles led to the exclusion of a further 395 studies, resulting in 65 articles assessed for eligibility. Finally, 11 studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], including 8 RCTs and 3 observational studies, were included in the systematic review and 5 of them (3 observational and 2 RCTs) in the meta-analysis. The process of study selection is represented in the PRISMA flow diagram ( Figure 1 ).…”

“…Considering the remdesivir group, two non-RCTs [ 15 , 16 ] reported a reduced mortality rate in favor of the combined treatment arm, and two other studies (an observational trial [ 14 ] and an RCT [ 18 ]) found a slight, non-significant, decreased mortality rate in the CCP-alone arm. In the TSUNAMI RCT [ 17 ], the mortality rate was included in the composite primary outcome, which was found similar between CCP-alone or combined groups.…”

“…Three studies evaluating CCP with or without remdesivir performed a safety analysis. While Moniuszko [ 14 ] reported no adverse effects, Koirala [ 15 ] and Arquiette [ 16 ] reported an incidence of treatment-related adverse effects of 5% and 10%, respectively. No safety data are available regarding studies on CCP with or without steroids.…”

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials

“…Results from previous studies suggested reduced mortality and improved symptoms in COVID-19 patients treated with COVID-19 convalescent plasma (CCP) (6,7), and the FDA of the United States had approved the emergency use authorization (EUA) of CCP in COVID-19 patients (8). However, these studies were mainly retrospective and contained potential risk of bias, while the results from prospective studies suggested that administration of CCP could not result in reduced risk of mortality or improved symptoms (9)(10)(11). Recent meta-analysis which included results from RCTs (8,12,13) also indicated no significant improvements in the survival of COVID-19 who received CCP.…”