Effect of SARS-CoV-2 seropositivity on antigen – specific cytokine and chemokine responses in latent tuberculosis

Abstract

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen – specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative with SARS-CoV-2 seropositivity and healthy controls (LTBI and SARS-CoV-2 negative). Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG+) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1β, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB – antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

Prevalence of indeterminate tuberculosis interferon‐gamma release assays in COVID‐19 patients: Systematic review and meta‐analysis

“…Disagreements were resolved through minor discussion and arbitration by the third investigator. Based on the eligibility criteria, 12 studies were included in the systematic review 10–12,17–25 . The screening flowchart demonstrated the study selection process in Figure 1.…”

“…Four studies were of good quality, 10,11,21,22 three studies were of fair quality, 12,17,18 and five studies were of poor quality 19,20,23–25 …”

“…All included studies used the QFT‐TB test. The QFT‐TB Plus kit was used in 10/12 studies (83.3%) corresponding to 1993 patients (94.6%), 10–12,17–20,22,23,25 and the QFT‐TB GIT kit in 2/12 studies (16.6%) corresponding to 114 patients (5.4%) 21,24 . No data was retrieved on TB‐SPOT or tuberculin test.…”

“… Inflammation‐related parameters, assessed in six studies, 10,12,18–20,24 were reported to be high in patients with indeterminate QFT‐TB test results including D ‐dimer, 12,18–20 CRP, 12,20 lactate dehydrogenase (LDH), 12,18,19 procalcitonin, 12 fibrinogen, 12,20 ferritin, 12,18,20 neutrophils count, 11,12,20 and IL‐6 12 Total lymphocyte count was assessed in 10 studies 10–12,18–22,24,25 . There was a significant association between lymphopenia and indeterminate QFT‐TB results or a low response to mitogen in seven studies 10,12,18–20,24,25 .…”

“…Total lymphocyte count was assessed in 10 studies 10–12,18–22,24,25 . There was a significant association between lymphopenia and indeterminate QFT‐TB results or a low response to mitogen in seven studies 10,12,18–20,24,25 .…”