Coinfection of tuberculosis and COVID-19 limits the ability to in vitro respond to SARS-CoV-2

Abstract

Objectives: The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI).

Methods: We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S).

Results: We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178).

Conclusions: Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.

Keywords: COVID-19; Co-infection; IFN-gamma response; M. tuberculosis; Tuberculosis; Whole blood assay.

Figure 1

Tuberculosis comorbidity impairs the SARS-CoV-2-specific immune response. Evaluation of the IFN-γ response to TB1 (A), TB2 (B), CD4S (C) and mitogen in COVID-19, TB-COVID-19, LTBI-COVID-19 and NO COVID-19 subjects. A. The IFN-γ level in COVID-19-patients was significantly lower compared to TB-COVID-19 and LTBI-COVID-19-patients in response to TB1. B. The IFN-γ level in COVID-19-patients was significantly lower compared to TB-COVID-19 and LTBI-COVID-19-patients in response to TB2. C. TB-COVID-19-patients showed the lowest IFN-γ levels in response to CD4-S compared to “COVID-19” patients and to LTBI-COVID-19-patients. D. No significant differences were found in response to the mitogen among the groups evaluated. Footnotes: Horizontal bars represent medians. IFN-γ was measured by ELISA in harvested stimulated plasma. Responses were compared using the Mann–Whitney test with Bonferroni correction; differences were considered significant at p-values of ≤0.05 or 0.016. Red dots indicate patients scored indeterminate to QFT-Plus. Blue p values indicate differences almost significant. COVID-19: CoronaVIrus Disease-2019; TB: tuberculosis; LTBI: latent TB infection; CD: cluster differentiation; MIT: mitogen.