Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome.

Xavier Solanich,Arnau Antolí,Celeste Basaez,Miguel Santin,Miguel Fernández-Huerta,Fernando Alcaide,Gemma Rocamora-Blanch,Xavier Corbella

doi:10.3390/jcm10050918

Abstract

Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March–April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002–1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397–14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%; p = 0.005). We conclude that QFT-Plus assay yielded an unexpected, high prevalence of indeterminate results in severe COVID-19 patients. Factors related to worse COVID-19 outcome, such as LDH, as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result. The role of an indeterminate QFT-Plus result in predicting COVID-19 severity and mortality should be evaluated.

Highlights

The QFT-Plus assay was indicated for the screening of latent tuberculosis infection (LTBI) in patients receiving or potentially going to receive immunosuppressive therapy to treat severe COVID-19
QFT-Plus test was performed with a median of 12 (IQR 10–16) days from the onset of COVID-19 symptoms
Factors related to worse COVID-19 outcome such as lactate dehydrogenase (LDH), as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result

Summary

Introduction

In December 2019, an emerging disease (COVID-19), caused by a newly identified human coronavirus, was first recognized in Wuhan, China, and spread worldwide [1,2]. The WHO declared the COVID-19 epidemic to be a pandemic on 12 March 2020 [3], and it continues to spread globally today, causing considerable morbimortality and economic damage. Reactivation of several dormant infections, including latent tuberculosis infection (LTBI), is of concern among COVID-19-treating physicians. In this regard, interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germany) [8] assay, have been unsystematically performed for LTBI screening in some severe COVID-19 patients, before or during immunosuppressive therapy

Objectives

Methods

Results

Discussion

Conclusion