Troponin and Other Biomarker Levels and Outcomes Among Patients Hospitalized With COVID-19: Derivation and Validation of the HA2T2 COVID-19 Mortality Risk Score

Abstract

Background The independent prognostic value of troponin and other biomarker elevation among patients with coronavirus disease 2019 (COVID-19) are unclear. We sought to characterize biomarker levels in patients hospitalized with COVID-19 and develop and validate a mortality risk score. Methods and Results An observational cohort study of 1053 patients with COVID-19 was conducted. Patients with all of the following biomarkers measured-troponin-I, B-type natriuretic peptide, C-reactive protein, ferritin, and d-dimer (n=446) -were identified. Maximum levels for each biomarker were recorded. The primary end point was 30-day in-hospital mortality. Multivariable logistic regression was used to construct a mortality risk score. Validation of the risk score was performed using an independent patient cohort (n=440). Mean age of patients was 65.0±15.2 years and 65.3% were men. Overall, 444 (99.6%) had elevation of any biomarker. Among tested biomarkers, troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P<0.001). Patients with a mortality score using hypoxia on presentation, age, and troponin-I elevation, age (HA₂T₂) ≥3 had a 30-day mortality of 43.7% while those with a score <3 had mortality of 5.9%. Area under the receiver operating characteristic curve of the HA₂T₂ score was 0.834 for the derivation cohort and 0.784 for the validation cohort. Conclusions Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30-day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19-associated mortality.

Keywords: COVID‐19; biomarkers; mortality; troponin.

Figure 1. Distribution of maximum biomarker levels among study patients.

A, TnI levels shown in logarithmic scale to allow depiction of distribution of troponin levels between 0 and 1.0 ng/mL. Dotted line depicts TnI level at 0.50 ng/mL. B, BNP levels. Patients with BNP ≥2000 pg/mL are grouped together. C, CRP levels. Patients with CRP ≥200 mg/dL are grouped together. D, Ferritin levels. Patients with ferritin ≥2000 ng/mL are grouped together. E, d‐Dimer levels. BNP indicates B‐type natriuretic protein; CRP, C‐reactive protein; and TnI, troponin I.

Figure 2. Receiver operating characteristic curves for biomarker levels and 30‐day in‐hospital mortality.

Graph lists AUC for respective curves and 95% CI. AUC indicates area under the curve; BNP, B‐type natriuretic protein; CRP, C‐reactive protein; and TnI, troponin I.

Figure 3. The HA₂T₂ score and its association with 30‐day in‐hospital mortality.

The HA₂T₂ score is calculated as follows: hypoxia upon presentation (defined as requiring supplemental oxygenation within 3 hours of arrival in emergency department)=1 point; age=1 point if 65 to 74 years and 2 points if ≥75 years; troponin 0.34 ng/mL ≥2 points. ds indicates days.

Figure 4. Kaplan‐Meier survival curves of patients hospitalized with coronavirus disease 2019 stratified by presence or absence of HA₂T₂ score ≥3.

Figure 5. Calibration plots of predicted probability vs observed probability of 30‐day in‐hospital mortality for the HA₂T₂ risk score model.

A, Calibration plot for derivation cohort (n=446). The calibration slope is 0.954 (SE 0.101) and calibration‐in‐large is 0.009 (SE 0.028). B, Calibration plot for validation cohort (n=440). The calibration slope is 0.952 (SE 0.162) and calibration‐in‐large is 0.008 (SE 0.038).