Association of Convalescent Plasma Treatment with Reduced Mortality and Improved Clinical Trajectory in Patients Hospitalized with COVID-19 in the Community Setting

Arnold Egloff, S. A.; Junglen, A.; Restivo, J. S. A.; Wongskhauluang, M.; Martin, C.; Doshi, P.; Schlauch, D.; Fromell, G.; Sears, L. E.; Correll, M.; Burris, H. A.; LeMaistre, C. F.

Background: Convalescent plasma (CP) quickly emerged as one of the first investigational treatment options for COVID-19. Evidence supporting CP for treating patients hospitalized with COVID-19 has been inconclusive, leading to conflicting recommendations regarding its use. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19. Methods: The matched, multicenter, electronic health records-based, retrospective cohort study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals across the United States from March 2 to October 7, 2020. Coarsened exact matching (1:k) was employed resulting in a sample of 3,774 CP and 10,687 comparison patients. Results: Examining mortality using a shared frailty model and controlling for concomitant medications, calendar date of admission, and days from admission to transfusion demonstrated a significant association of CP with lower risk of mortality compared to the comparison group (aHR = 0.71, 95% CI 0.59-0.86, p<0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our Real-Time Risk Model (RTRM), indicated that patients who received CP recovered more quickly. The time from admission to CP transfusion was significantly associated with risk of mortality and stratification revealed that CP within 3 days after admission, but not 4-7 days, was associated with a significant reduction in mortality risk (aHR = 0.53, 95% CI 0.47-0.60, p<0.001). CP serology level was inversely associated with mortality when controlling for interaction with days to transfusion (HR = 0.998, 95% CI 0.997-0.999, p = 0.013) but was not significant in a univariable analysis. Conclusion: Utilizing this large, diverse, multicenter cohort, we demonstrate that CP is significantly associated with reduced risk of in-hospital mortality. These observations demonstrate the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19. Funding: This research was supported, in whole, by HCA Healthcare and/or an HCA Healthcare affiliated entity including Sarah Cannon and Genospace.