RESUMO
Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in a low and middle income country setting such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than in the SOC group (21% versus 39%; Fishers exact P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% CI, 0.18-0.66; P = 0.001), while complication of acute renal failure (creatinine levels >110 mol/L; HR, 4.45; 95%CI, 2.54-7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, IQR -4 to -1) was significantly greater than in the SOC group (median -1 point, IQR -3 to 1, Mann Whitney P = 0.0004). Improvement in PaO2/FiOs ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann Whitney P = 0.0234). Further research is needed for HemoClear-produced CCP as therapy in SARS-CoV-2 infections together with adequately powered, randomized controlled trials. ImportanceThis study compares mortality and other endpoints between intensive care unit (ICU) COVID-19 patients treated with convalescent plasma plus standard of care (CCP), and a control group of patients hospitalized in the same medical ICU facility treated with standard of care alone (SOC) in a low and middle income country (LMIC) setting using bedside donor whole blood separation by gravity (HemoClear) to produce the CCP. It demonstrates a significant 65% survival improvement in HemoClear-produced CCP recipients (HR 0.35; 95% CI, 0.19-0.66; P = 0.001). Although this is an exploratory study, it clearly shows the benefit of using the HemoClear-produced CCP in ICU patients in the Suriname LMIC setting. Additional studies can further substantiate our findings and their applicability to both LMICs and high income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.
RESUMO
BackgroundAlthough 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 life-threatening 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 x-ray (CXR) score. FindingsThe 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. InterpretationAmong 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-randomized design of the trial, these results offer a potential route for broader implementation of CP treatment in LMICs. FundingThis study was funded by the Academic Hospital Paramaribo, without additional third-party funding.
