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Tuberculosis - Dysregulated IFN-γ, IL-6 and TNF-α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB

sharon sanders

Editor-in-Chief & President
Dysregulated IFN-γ, IL-6 and TNF-α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB

Author links open overlay panelUzair Abbas [SUP]1[/SUP] [SUP]2[/SUP], Kiran Iqbal Masood [SUP]1[/SUP], Tulaib Iqbal [SUP]1[/SUP], Shama Qaiser [SUP]1[/SUP], Martin Rottenberg [SUP]3[/SUP], Bushra Jamil [SUP]4[/SUP], Rabia Hussain [SUP]1[/SUP], Zahra Hasan [SUP]1[/SUP]

https://doi.org/10.1016/j.tube.2025.102718Get rights and content
Under a Creative Commons license
Open access


Highlights

  • SARS-CoV-2 Spike stimulation induced lower IL-2, IL-6 and IFN-γ in COVID-19.

  • IGRA positive Controls showed higher activation of IFN-γ, IL-2, IL-6, IL-1β, and IL-5

  • MTB-induced cytokine activation was decreased in COVID-19

  • Dysregulation IL-6/IL-10 and TNF-α/IL-10 ratio in IGRA positive COVID-19 group participants

  • Reduced cytokine activation after COVID-19 may increase chance of LTBi reactivation.
Abstract

SARS-CoV-2 infection modulates innate and adaptive immunity and likely impacts outcomes of infections such as Mycobacterium tuberculosis (MTB). We investigated the association between COVID-19 and latent tuberculosis infection (LTBi), studying viral and mycobacterial antigen-stimulated responses in those with and without a history of COVID-19.
We studied healthy Controls and COVID-19 convalescent subjects. Participants were screened for LTBi using an interferon-gamma release assay (IGRA). SARS-CoV-2 Spike- and MTB H37Rv-sonicate -stimulated cytokines from peripheral blood mononuclear cells (PBMCs) were measured.
Spike-induced IFN-γ (p=0.03), IL-6 (p=0.018) and IL-2 (p=0.04) levels were reduced in COVID-19 as compared with Controls. Within Controls, Spike-induced higher cytokine levels in IGRA positive participants (p<0.05). MTB-induced IFN-γ (0.003), IL-2 (p=0.0021), IL-6 (p=0.002), TNF-α (p=0.02), and IL-10 (p=0.04) levels were lowered in COVID-19. Spike- and MTB- stimulated higher levels of proinflammatory cytokines in IGRA-positive Controls. Between IGRA positive participants, the COVID-19 group displayed lower Spike and MTB induced IFN-γ (0.003), IL-6 (0.0037), IL-2 (0.001), and TNF-α (0.005) levels. Further, MTB-induced IL-6/IL-10 and TNF-α/IL-10 ratios were higher in COVID-IGRA positive participants.
Reduced SARS-CoV-2 and MTB activation of inflammatory cytokines reflects downregulated immunity after COVID-19. Further studies are required to assess whether LTBI and COVID-19 increase the risk of progression to tuberculosis.

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6. Conclusions

In conclusion we identify an altered immune response to both SARS-CoV-2 and MTB in participants with a history of COVID-19. We observed that both pro- and anti-inflammatory cytokines were found to be dysregulated in those who had suffered COVID-19 and who had latent TB infection. These findings are of relevance in TB-endemic regions, where the overlap of COVID-19 and TB can influence disease progression and surveillance. Longitudinal studies are warranted to determine the clinical implications of reduced MTB-specific immunity in post-COVID individuals and whether this increases risk of reactivation.​

more....https://www.sciencedirect.com/science/article/pii/S1472979225001131
 
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