key: cord-0960778-37sf9y59
authors: Kittanakom, Saranya; Kavsak, Peter A
title: Combination of lymphocyte count and not the serological response with high-sensitivity cardiac troponin for risk stratification in patients with possible COVID-19
date: 2021-05-21
journal: Clin Chim Acta
DOI: 10.1016/j.cca.2021.05.018
sha: 13ca652734c8a20272b4890e418af1d5d893f418
doc_id: 960778
cord_uid: 37sf9y59

Combination of lymphocyte count and not the serological response with high-sensitivity cardiac troponin for risk stratification in patients with possible COVID-19

Letter to the Editor Combination of lymphocyte count and not the serological response with high-sensitivity cardiac troponin for risk stratification in patients with possible COVID-19.

Hospital systems are still struggling with a surge in patients with possible COVID-19. The detection of the SARS-CoV-2 virus is important for both patient management and resource allocation. However, additional laboratory testing may also provide an important role in risk stratification for patients with possible COVID-19 [1, 2] . Within the last year the development and utility of serological tests for SARS-CoV-2 has been largely focused outside acute care management (with the exception of the diagnostic work-up of multisystem inflammatory syndrome in children) [2] . There has been interest in assessing serological testing for convalescent plasma donors and in assessing the antibody response in patients with COVID-19, but very little data exists regarding its utility in acute care management and for risk stratification in patients without vaccination. Herein, we have undertaken an exploratory study to assess if the combination of high-sensitivity cardiac troponin (hs-cTn) with other important laboratory parameters (i.e., creatinine, lymphocyte count, neutrophil count, and antibodies that target the S1 RBD antigen) [1] [2] [3] can be used for risk stratification for patients with possible COVID-19.

After research ethics board approval, left over lithium heparin plasma samples from patients tested for SARS-CoV-2 (nasopharyngeal swab with reverse transcription polymerase chain reaction; RT-PCR testing performed for the virus) were obtained on a weekly basis over 6 months (April to October 2020 with samples frozen <-20 0 C). The samples were tested for hs-cTnI, immunoglobulin isotype G (IgG) and total immunoglobulin 2/7 (total: IgG and IgM) for SARS-CoV-2 (Siemens Atellica platform with results reported in ng/l for hs-cTnI and as the numeric index for the antibody assays) with only patients that had plasma creatinine, a complete blood count and the three Atellica tests (hs-cTnI, IgG and total: IgG & IgM) measured in the admission sample included in the analysis (n = 302 patients). The outcome was in-hospital death (n = 53) with receiver-operating characteristic Combining other laboratory tests with hs-cTnI may further improve the sensitivity and specificity for predicting mortality in patients with COVID-19 [5] . To this end we combined the biomarker with the next highest AUC (lymphocyte count using a published cutoff of 1.5 × 10 9 cells/l) [1] with hs-cTnI to further classify low risk patients (i.e., hs-cTnI 3/7 < 5 ng/l and lymphocyte count ≥ 1.5 × 10 9 /l) and high risk patients (hs-cTnI ≥ 120 ng/l and lymphocyte count < 1.5 × 10 9 /l). Applying both biomarkers using these cutoffs increased the point estimates for sensitivity (98.1%; 95%CI: 89.9-99.9) and specificity (95.2%; 95%CI: 91.7-97.5) (Fig. 1) . Assessing this test combination in only patients who were PCR positive for SARS-CoV-2 (n = 269) further increased the sensitivity/negative predictive value (100% for both parameters) and specificity/positive predictive value (96.7%/61.1%) estimates.

Nearly 25% (n = 67) of this population would be deemed low risk with no in-hospital deaths.

However, this test combination of hs-cTnI and the lymphocyte count was less effective in patients who were PCR negative for SARS-CoV-2 (n = 33) with a sensitivity of 87.5% and specificity of 80.0%.

This exploratory analysis has identified that patients with possible COVID-19 with a hs-cTnI concentration < 5 ng/l with a concomitant lymphocyte count ≥ 1.5 × 10 9 per liter represents a population unlikely to die during hospital stay (negative likelihood ratio of 0.064; 95%CI: 0.009-0.453). In fact, this test combination performance may be improved if evaluated in only patients who are PCR positive for SARS-CoV-2. These data provide additional proof in concept that a combination of laboratory tests may be helpful for risk and resource stratification in patients with possible COVID-19 [1, 5] . Importantly, our data does not demonstrate any benefit for serological testing for SARS-CoV-2 regarding risk stratification in the hospital setting for patients without vaccination for SARS-CoV-2.

Additional studies assessing the utility of serological testing in patients presenting with possible COVID-19 symptoms who have been vaccinated or who have previously recovered from COVID-19 are needed. 6/7 

Emerging key laboratory tests for patients with COVID-19

Editorial and Executive Summary: IFCC Interim Guidelines on Clinical Laboratory testing during the COVID-19 Pandemic

Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results

Myocardial Infarction Risk Stratification With a Single Measurement of High-Sensitivity Troponin I

Admission High-Sensitivity Cardiac Troponin vs a Biochemical Score for Predicting Mortality in Patients With COVID-19. CJC Open