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

Document Type

Article

Department

Medicine; Pathology and Laboratory Medicine

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. MTB- stimulated higher levels of proinflammatory cytokines were found 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.

AKU Student

no

Publication (Name of Journal)

Tuberculosis

DOI

10.1016/j.tube.2025.102718

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