TY - JOUR
T1 - Individuals with latent tuberculosis in a high TB endemic country show mild COVID-19
AU - Abbas, Uzair
AU - Masood, Kiran Iqbal
AU - Iqbal, Tulaib
AU - Jamil, Bushra
AU - Qaiser, Shama
AU - Yameen, Maliha
AU - Rottenberg, Martin
AU - Hussain, Rabia
AU - Hasan, Zahra
N1 - Publisher Copyright:
Copyright: © 2025 Abbas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2025
Y1 - 2025
N2 - INTRODUCTION: Infection with Mycobacterium tuberculosis (MTB) may result in active tuberculosis (TB), bacterial clearance, or asymptomatic latent infection (LTBi). During the COVID-19 pandemic, interactions between MTB and SARS-CoV-2 infections were coincident in high TB burden countries such as Pakistan. The impact of LTBi on COVID-19 is not well understood. Here we investigated the association of LTBi with COVID-19 and its severity by determining cellular activation to MTB, IgG antibody responses and expression of genes associated with host immunity. METHODS: Age and sex matched Healthy Controls (HC, n = 147) and COVID-19 patients (n = 128) were recruited in this cross-sectional study. COVID-19 was categorized as ambulatory (n = 103) or hospitalized (n = 25) disease. LTBi was determined using the X.DOT-TB ELISpot assay. RT-PCR based mRNA levels of IFN-γ, IFN-α, IL-6, IL-10, OAS1, MAVS, SOCS1 and SOCS3 were determined in PBMCs. IgG to SARS-CoV-2 and rubella virus were measured. RESULTS: We found that 18% of COVID-19 patients and 32% of HC were LTBi positive (p < 0.0001). All COVID-19 LTBi positive cases had ambulatory disease. Logistic regression analysis revealed individuals with LTBi to have a 54% lower risk of COVID-19. The frequency of MTB-specific IFN-γ producing T cells was lower in COVID-19 patients than in HC LTBi positive individuals (p = 0.0095). The presence of a BCG scar was not associated with the occurrence of COVID-19. Levels of IgG antibodies to SARS-CoV-2 were raised in COVID-19 cases but did not differ by LTBi status in HC or COVID-19 groups. IgG levels to rubella virus were similar regardless of LTBi status in control and patient groups. COVID-19 cases displayed higher expression of mRNA levels of MAVS, OAS-1, and SOCS3 (p < 0.05). Further, OAS-1 expression was raised in LTBi positive COVID-19 group as compared to the LTBi positive HC group (p = 0.019). CONCLUSIONS: We observed that T cell reactivity to MTB was associated with milder COVID-19. Reduced severity of COVID-19 and higher OAS-1 gene expression in COVID-19 LTBi positive individuals suggest a protective effect in these individuals. Further studies are required to investigate the combined impact of MTB and SARS-CoV-2 infections in the host.
AB - INTRODUCTION: Infection with Mycobacterium tuberculosis (MTB) may result in active tuberculosis (TB), bacterial clearance, or asymptomatic latent infection (LTBi). During the COVID-19 pandemic, interactions between MTB and SARS-CoV-2 infections were coincident in high TB burden countries such as Pakistan. The impact of LTBi on COVID-19 is not well understood. Here we investigated the association of LTBi with COVID-19 and its severity by determining cellular activation to MTB, IgG antibody responses and expression of genes associated with host immunity. METHODS: Age and sex matched Healthy Controls (HC, n = 147) and COVID-19 patients (n = 128) were recruited in this cross-sectional study. COVID-19 was categorized as ambulatory (n = 103) or hospitalized (n = 25) disease. LTBi was determined using the X.DOT-TB ELISpot assay. RT-PCR based mRNA levels of IFN-γ, IFN-α, IL-6, IL-10, OAS1, MAVS, SOCS1 and SOCS3 were determined in PBMCs. IgG to SARS-CoV-2 and rubella virus were measured. RESULTS: We found that 18% of COVID-19 patients and 32% of HC were LTBi positive (p < 0.0001). All COVID-19 LTBi positive cases had ambulatory disease. Logistic regression analysis revealed individuals with LTBi to have a 54% lower risk of COVID-19. The frequency of MTB-specific IFN-γ producing T cells was lower in COVID-19 patients than in HC LTBi positive individuals (p = 0.0095). The presence of a BCG scar was not associated with the occurrence of COVID-19. Levels of IgG antibodies to SARS-CoV-2 were raised in COVID-19 cases but did not differ by LTBi status in HC or COVID-19 groups. IgG levels to rubella virus were similar regardless of LTBi status in control and patient groups. COVID-19 cases displayed higher expression of mRNA levels of MAVS, OAS-1, and SOCS3 (p < 0.05). Further, OAS-1 expression was raised in LTBi positive COVID-19 group as compared to the LTBi positive HC group (p = 0.019). CONCLUSIONS: We observed that T cell reactivity to MTB was associated with milder COVID-19. Reduced severity of COVID-19 and higher OAS-1 gene expression in COVID-19 LTBi positive individuals suggest a protective effect in these individuals. Further studies are required to investigate the combined impact of MTB and SARS-CoV-2 infections in the host.
UR - https://www.scopus.com/pages/publications/105026437639
U2 - 10.1371/journal.pone.0339240
DO - 10.1371/journal.pone.0339240
M3 - Article
C2 - 41468475
AN - SCOPUS:105026437639
SN - 1932-6203
VL - 20
SP - e0339240
JO - PLoS ONE
JF - PLoS ONE
IS - 12
ER -
