Reduced Mortality among COVID-19 ICU Patients after Treatment with HemoClear Convalescent Plasma in Suriname

Abstract

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in low- and middle-income country settings such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as a 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 that in the SOC group (21% versus 39%; Fisher's exact test P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.18 to 0.66; P = 0.001), while complication of acute renal failure (creatinine levels, >110 mol/L; HR, 4.45; 95% CI, 2.54 to 7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, interquartile range [IQR] -4 to -1) was significantly greater than that in the SOC group (median -1 point, IQR -3 to 1, Mann-Whitney test P = 0.0004). Improvement in the PaO₂/FiO₂ 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 a therapy for SARS-CoV-2 infection together with adequately powered, randomized controlled trials. IMPORTANCE This study compares mortality and other endpoints between intensive care unit 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 to 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 could further substantiate our findings and their applicability for both LMICs and high-income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.

Keywords: COVID-19; HemoClear; ICU; SARS-CoV-2; convalescent plasma; mortality.

FIG 1

Identification of covariates to be included in multivariate analyses. Univariate Cox proportional analyses of hospital days (purple diamonds) and intensive care unit (ICU) days (blue diamonds) were performed for factors which might have affected in-hospital mortality. Graph depicts hazard ratios with 95% confidence intervals (CI). Log-rank P values are shown. Variables in bold were significantly associated with death and included in the multivariate Cox proportional hazard analyses.

FIG 2

Multivariate analyses of covariates for in-hospital mortality. A multivariate Cox proportional hazard analysis was performed with the univariately significant variables for hospital days (purple diamonds) and ICU days (blue diamonds). Graph depicts hazard ratios with 95% CI. Log-rank P values are shown.

FIG 3

Survival probability during hospital admission for CCP and SOC treatment groups. (A) Kaplan-Meier curve of ICU days for CCP and SOC treatment groups. Right-censoring took place when a person was dismissed from the ICU before the last measured time point; death was counted as an event. Log-rank (Mantel-Cox) P < 0.001. The longest ICU admission duration was 27 days for the CCP group, while it was 50 days for the SOC group. (B) Kaplan-Meier curve of hospital days for CCP and SOC treatment groups. Right-censoring took place when a person was dismissed from hospital before the last measured time point; death was counted as an event. Log-rank (Mantel-Cox) P = 0.013. The longest hospital admission duration was 37 days in the CCP group and 62 days in the SOC group. Survival analysis was cut off when there were ≤1 patients at risk remaining in at least one of the two groups, at 28 ICU days and at 35 hospital days, respectively.

FIG 4

Chest radiographic findings (CXR) score and pulmonary oxygen exchange capacity (P/F) ratio improvement in CCP and SOC treatment groups. The delta CXR and delta PFR were calculated by subtracting the respective scores on day 0 from those on day 2. Graphs show minimum, median, interquartile range, and maximum for each group. (A) The CCP group showed significantly greater improvement in CXR score than the SOC group (Mann-Whitney test). (B) The CCP group showed significantly greater improvement in P/F ratio than the SOC group (Mann-Whitney test).

FIG 5

Patient selection flowchart with study enrollment and design. Standard of care treatment group (SOC): oral or intravenous dexamethasone once daily. COVID convalescent plasma group (CCP): 2 units of COVID-19 convalescent plasma. Each unit was infused over a period of at least 30 min, with close observation for the entire duration. Adverse events were medicated (anaphylaxis, antihistamines, corticosteroids, and epinephrine) within reach.