key: cord-0716416-jw6cfcjy
authors: Smilowitz, Nathaniel R.; Nguy, Vuthy; Aphinyanaphongs, Yindalon; Newman, Jonathan D.; Xia, Yuhe; Reynolds, Harmony R.; Hochman, Judith S.; Fishman, Glenn I.; Berger, Jeffrey S.
title: Multiple Biomarker Approach to Risk Stratification in COVID-19
date: 2021-02-15
journal: Circulation
DOI: 10.1161/circulationaha.120.053311
sha: e6b5c6af784a4c79f060ccc02fe4ded40cc244da
doc_id: 716416
cord_uid: jw6cfcjy

nan

elevated in 2243 (77.5%), and CRP was >50 mg/L in 2261 (78.1%). Only 196 (6.8%) patients had normal cTn, normal D-dimer, and a CRP of <50 mg/L (no elevated biomarkers). Elevations of all 3 biomarkers, reflecting the pathobiological axes of myocardial injury, coagulation, and inflammation, were present in 334 (11.5%; Figure) . Patients with no elevated biomarkers were at low risk of critical illness and in-hospital mortality. Continuous CRP (C-statistic, 0.611 [95% CI, 0.587-0.634]), D-dimer (C-statistic, 0.639 [95% CI, 0.615-0.664]), and troponin (C-statistic, 0.680 [95% CI, 0.655-0.705]) concentrations were each separately associated with mortality. Patients with 1, 2, or 3 elevated biomarkers had stepwise increases in the risk of adverse events (Figure) . The number of elevated biomarkers alone yielded a C-statistic of 0.672 (95% CI, In this analysis of patients with COVID-19, 93% had myocardial injury, abnormalities in coagulation, or marked inflammation at hospital presentation. The combination of abnormalities across these pathobiological axes of disease provided incremental prognostic information for risk stratification. Patients with 1, 2, and 3 elevated biomarkers had 3-, 6-, and 11-fold Figure. The frequency of elevated biomarkers reflecting myocardial injury, coagulation, and inflammation in COVID-19 and associations with inhospital outcomes. A, Venn diagram illustrating overlap of elevated biomarkers at the time of initial hospital presentation in patients with COVID-19 and ≥1 elevated biomarker (n=2699). One hundred ninety-six patients had no elevated biomarkers. The proportion of patients with in-hospital mortality (B) and critical illness (C) are shown stratified by the number of elevated biomarkers measured at hospital presentation with COVID-19. Odds ratios (versus 0 biomarkers elevated) shown in B and C are adjusted for age, sex, race, body mass index, tobacco use, hypertension, hyperlipidemia, diabetes, chronic kidney disease, prior myocardial infarction, prior heart failure, atrial fibrillation, temperature at presentation, pulse oximetry at presentation, and outpatient prescriptions for antiplatelets, statin, and β-blockers. aOR indicates adjusted odds ratio; and CRP, C-reactive protein.

higher adjusted odds of death, respectively, compared with patients who had COVID-19 with no elevated biomarkers at presentation. These findings extend prior observations on the prognostic nature of these biomarkers in COVID-19 and provide a framework for rapid estimation of risk.

This study was retrospective, and selection bias cannot be excluded. Only in-hospital events were recorded. We used dichotomous biomarker data to generate a simple scoring system for clinical use. A threshold higher than the ULN was selected for CRP, myocardial injury was defined by site-specific values for the cTn ULN, and highsensitivity cTn assays were not used. Last, a separate validation cohort was not available. Still, a simple multimarker strategy, in which patients are categorized based on the number of elevated biomarkers, was effective to identify patients at risk for in-hospital adverse events. 

Prevalence and outcomes of D-dimer elevation in hospitalized patients with CO-VID-19

Myocardial injury in adults hospitalized with COVID-19

C-reactive protein and clinical outcomes in patients with COVID-19

Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD

Diagnostic utility of C-reactive protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study

Dr Smilowitz is supported, in part, by the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant no. K23HL150315). Dr Newman is funded, in part, by the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant no. K23HL125991). Dr Berger is funded, in part, by the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant no. R01HL139909 and R35HL144993).

Dr Smilowitz reports consulting for Abbott Vascular. The remaining authors report no conflicts.