Characterization of the immune impairment of tuberculosis and COVID-19 coinfected patients.

OBJECTIVES: To characterize the plasma immune profile of patients with TB-COVID-19 compared to COVID-19, TB or healthy controls and to in vitro evaluate the specific responses to SARS-CoV-2- and Mtb-antigens.

METHODS: We enrolled 119 subjects: 14 TB-COVID-19, 47 COVID-19, 38 TB, and 20 controls. Plasmatic levels of 27 immune factors were measured at baseline using a multiplex assay. The specific response to SARS-CoV-2- and Mtb-antigens was evaluated using a home-made whole-blood platform and QuantiFERON-Plus tubes, respectively.

RESULTS: We found an immune signature (TNF-α, MIP-1β, and IL-9) associated with TB-COVID-19 coinfection compared with COVID-19 (p<0.05) and TNF-α showed the highest discriminant power. We also found another signature (TNF-α, IL-1β, IL-17A, IL-5, FGF-basic, and GM-CSF) in coinfected compared with TB patients (p<0.05), and among them TNF-α and GM-CSF showed a non-negligible discriminating ability. Moreover, coinfected patients showed significantly reduced SARS-CoV-2 specific response compared with COVID-19 for several pro-inflammatory cytokines/chemokines, anti-inflammatory cytokines and growth factors (p≤0.05). Furthermore, coinfection negatively affected the Mtb-specific response (p≤0.05).

CONCLUSIONS: We found immune signatures associated with TB-COVID-19 coinfection and observed a major impairment of SARS-CoV-2-specific and to a lesser extent the Mtb-specific immune responses. These findings further advance our knowledge of the immunopathology of TB-COVID-19 coinfection.