Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19
Shanna A. Arnold Egloff, … , Howard A. Burris III, Charles F. LeMaistre
Shanna A. Arnold Egloff, … , Howard A. Burris III, Charles F. LeMaistre
Published August 31, 2021
Citation Information: J Clin Invest. 2021;131(20):e151788. https://doi.org/10.1172/JCI151788.
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Clinical Research and Public Health Infectious disease

Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

Abstract

BACKGROUND Evidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. 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 multicenter, electronic health records–based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare–affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTS Examination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [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 stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower 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 its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997–0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONS This large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight 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.

Authors

Shanna A. Arnold Egloff, Angela Junglen, Joseph S.A. Restivo, Marjorie Wongskhaluang, Casey Martin, Pratik Doshi, Daniel Schlauch, Gregg Fromell, Lindsay E. Sears, Mick Correll, Howard A. Burris III, Charles F. LeMaistre

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Figure 2

Real-time risk curves as a visual of daily patient risk trajectories.

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Real-time risk curves as a visual of daily patient risk trajectories. RT...
RTRM curves, smoothed and weighted, showing risk trajectories across CP and the comparison group. A generalized additive model with integrated smoothness estimation was applied to the risk predictions over hospitalization time, which were anchored by baseline date. Patients at discharge were assigned a final RTRM probability based on vital status of 1.00 for expired and 0.00 for alive. Shaded boundaries around each curve represent the 95% CIs. (A) Main weighted comparison of the RTRM-matched cohort of CP (orange) and the comparison (blue) groups. (B) Weighted comparison of CP (orange) and comparison (blue) groups stratified by intubation (dotted) versus no intubation (solid) at any point during hospitalization, excluding intubation within 48 hours after admission. Note, this is different from the intubation subgroup analysis where intubation was defined as having occurred prior to or on the day of transfusion or pseudo-baseline, excluding patients intubated within the first 48 hours of admission. (C) Compilation of weighted comparisons between CP (orange) and the comparison (blue) groups for each of the two 0 to 3 (dotted) and 4 to 7 (solid) days from admission to transfusion groupings.