Longitudinal Evaluation of the QuantiFERON-TB Gold Plus Assay in Hospitalized COVID-19 Patients with a First Indeterminate Result: Resolution of Inflammation and Restoration of T-Lymphocyte Counts and Interferon-Gamma Production

everal studies report an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) results in patients hospitalized because of severe Coronavirus Disease (COVID)-19, and this is due to peripheral blood T-lymphocyte depletion and dysfunction (1-6), which are known to be associated with COVID-19 disease severity and mortality (7-9).So far, there are no reports concerning QFT-P responses and relations with lymphocyte counts or inflammation markers in subjects who survived COVID-19 and received a previous indeterminate result after the acute phase of the disease.For this reason, patients hospitalized because of COVID-19 from March 2020 to August 2021 in the Infectious Disease Unit of Policlinico Tor Vergata University Hospital in Rome who received an indeterminate QFT-P test during hospitalization were recalled for reassessment after recovery in the post-COVID outpatient clinic.Those who gave written informed consent were enrolled in the study.Collection tubes for the QFT-P test were purchased from Qiagen, and the interferon gamma (IFN-g) levels were assessed via chemiluminescence immunoassay using the Liaison XL Analyzer.In a subgroup of patients, peripheral blood lymphocyte subsets were also reassessed.Demographics, clinical data, and laboratory data were collected.The study was approved by the local Ethics Committee (protocol number 125.21).All statistical analyses were performed using GraphPadPrism.Comparisons between groups were performed via a nonparametric test for paired data (Wilcoxon), and a P value of ,0.05 was regarded as indicative of a statistically significant result.36 patients were enrolled, and the sample presented with a median age of 58 (interquartile range [IQR]: 51 to 63) years and a prevalence of males (M/F: 24/12).Considering disease severity, 30 patients were classified as severe (needing high flux oxygen or noninvasive or invasive ventilation), and 6 were classified as nonsevere.1 patient needed admission to the intensive care unit (ICU).The median Charlson comorbidity index was 2 (IQR:1 to 3) (Table 1).A second QFT-P assay was performed at least 43 days after the first assay (median time: 200 days; IQR: 154 to 352 days).All of the QFT-P assays gave an interpretable (determinate) result, with 2 positive (5.6%) and 34 negative (94.4%) tests.The laboratory parameters were reassessed and compared to the corresponding values registered at the time of COVID-19 hospitalization, including the absolute counts of total lymphocytes (P , 0.0001) CD3 1 , CD31CD4 1 , and CD31CD8 1 .T-lymphocytes were significantly increased (P = 0.0005), while the absolute count of neutrophils, the neutrophil to lymphocyte (N/L) ratio, and the D-dimer, fibrinogen, ferritin, and C-reactive protein (CRP) concentrations were significantly reduced (P , 0.0001) after hospital discharge.Concerning the QFT-P assay, IFN-g production