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Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with
Shanna A Arnold Egloff1,2, Angela Junglen1,2,3, Joseph Sa Restivo2
1Sarah Cannon, Nashville, Tennessee, USA.
Insights
Convalescent plasma (CP) significantly reduced in-hospital mortality for COVID-19 patients in a large retrospective study. Early CP treatment, within 3 days of admission, showed the greatest survival benefit, highlighting its potential therapeutic value.
Area of Science:
- Infectious Diseases
- Hematology
- Epidemiology
Background:
- Convalescent plasma (CP) was an early investigational treatment for coronavirus disease 2019 (COVID-19).
- Evidence for CP's effectiveness has been inconclusive, resulting in conflicting clinical recommendations.
- A comparative effectiveness study was needed to evaluate CP's impact on COVID-19 mortality.
Purpose of the Study:
- To conduct a comparative effectiveness study of convalescent plasma (CP) for all-cause, in-hospital mortality in COVID-19 patients.
- To analyze the association between CP administration and patient mortality risk.
- To investigate the impact of timing and serology levels of CP on patient outcomes.
Main Methods:
- A retrospective, multicenter cohort study involving 44,770 patients hospitalized with COVID-19.
- Utilized electronic health records from 176 HCA Healthcare-affiliated hospitals.
- Employed coarsened exact matching (1:k) to create comparable groups of 3,774 CP recipients and 10,687 controls, controlling for clinical and demographic factors.
Main Results:
- Convalescent plasma was significantly associated with a lower risk of in-hospital mortality (adjusted hazard ratio [aHR] = 0.71; P < 0.001).
- Patients receiving CP showed faster recovery trajectories.
- CP administered within 3 days of admission demonstrated a significantly lower mortality risk (aHR = 0.53; P < 0.001), while treatment between 4-7 days did not show a significant benefit.
Conclusions:
- This large-scale, real-world evidence study demonstrates that convalescent plasma is associated with reduced in-hospital mortality in COVID-19 patients.
- Early administration of CP (within 3 days) is crucial for achieving significant mortality benefits.
- Further evaluation of CP as a viable COVID-19 therapy is warranted, challenging premature abandonment.
Abstract:
BACKGROUNDEvidence 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.METHODSThe 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.RESULTSExamination 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.CONCLUSIONSThis 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.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.
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