Mortality reduction in ICU-admitted COVID-19 patients in Suriname after treatment with convalescent plasma acquired via gravity filtration

Abstract

Background Although convalescent plasma (CP) treatment is a potential therapeutic option for patients with COVID-19, there is a paucity of data from studies in low-resource settings. The efficacy and safety of CP therapy in intensive care unit (ICU) patients with COVID-19 in Suriname was evaluated. A novel gravity-based filtration method was used to obtain CP. The design was an open-label, multi-centre, non-randomized prospective clinical trial performed in two hospitals in Suriname, from June 2020, to December 2020. A pre-planned interim analysis is reported in 78 PCR-confirmed COVID-19 patients admitted to the ICU with severe or lifethreatening symptoms. CP in combination with standard treatment (n = 28) was compared to standard treatment alone (control) (n = 50), stratified by disease severity. The primary endpoint was 28-day ICU mortality. Secondary (exploratory) endpoints were changes two days after treatment initiation in pulmonary oxygen exchange capacity (PF ratio) and chest xray (CXR) score. Findings The median age of patients was 52 years with 43 [55.1%] being male. Twenty-eight day mortality occurred in 18% (5/28) of the CP group vs 36% (18/50) of the control group. Survival probability was significantly higher in the CP group compared to the control group with standard care (P=0.027). When stratifying into disease severity, the survival probability was the lowest for the control group with life-threatening disease (P=0.0051). CP treatment of severe COVID-19 resulted in a higher probability of survival, with a hazard ratio (HR) of 0.22 (95% CI, 0.074-0.067), correcting for age, the presence of diabetes and COVID-19 severity. Age significantly increased the mortality risk (HR, 1.08 [95%CI, 1.022-1.14]; P =0.006). In the severe group, CP resulted in an improved CXR score (P =0.0013) and increase in PF ratio (P = 0.011) as compared to standard therapy. The gravity-based plasmapheresis method used for CP production was well-tolerated and no adverse events were observed in the donors. Interpretation Among patients with severe or life-threatening COVID-19, CP therapy in combination with standard treatment resulted in 78% reduction of 28-day ICU mortality (HR = 0.22) compared to standard treatment alone. Both CXR-score and PF ratio changes represent indicators of treatment effect of CP after two days and can easily be implemented in low-resource settings. The novel CP production method was effective and represents a practical solution for low and middle income countries (LMICs) to produce CP locally. Although interpretation is limited by the non-randomised design of the trial, these results offer a potential route for broader implementation of CP treatment in LMICs.