The COVID-19 and TB syndemic: the way forward

Abstract

Together, SARS-CoV-2 and M. tuberculosis have killed approximately 5.7 million people worldwide over the past 2 years. The COVID-19 pandemic, and the non-pharmaceutical interventions to mitigate COVID-19 transmission (including social distancing regulations, partial lockdowns and quarantines), have disrupted healthcare services and led to a reallocation of resources to COVID-19 care. There has also been a tragic loss of healthcare workers who succumbed to the disease. This has had consequences for TB services, and the fear of contracting COVID-19 may also have contributed to reduced access to TB services. Altogether, this is projected to have resulted in a 5-year setback in terms of mortality from TB and a 9-year setback in terms of TB detection. In addition, past and present TB disease has been reported to increase both COVID-19 fatality and incidence. Similarly, COVID-19 may adversely affect TB outcomes. From a more positive perspective, the pandemic has also created opportunities to improve TB care. In this review, we highlight similarities and differences between these two infectious diseases, describe gaps in our knowledge and discuss solutions and priorities for future research.

Figure

Illustrative mechanism of SARS-COV-2 and TB interplay inside the host. Immunological response to M. tuberculosis and SARS-COV-2 includes role of both innate and adaptive immunity. SARS-COV-2 virus first activates dendritic cells resulting in the stimulation of lymphocytes such as B-cell, CD4+ and CD8+ cells; CD4+ and CD8+ cells in turn stimulate the Th1, Treg as well as, Th17 cells, resulting in an increase in IL-10 and decrease in cytokines IL-22, IL-17 and IFN-γ level. Reduced level of IFN-γ increases the susceptibility to bacterial infections and TB. The bacteria engulfed by the alveolar macrophages lead to an increase in IL-10, TNF-α, IFN-α, β and γ which further suppresses neutrophils, NK cells and Th17 cells. Suppression of neutrophils leads to the decrease in phagocytosis, release of NET and ROS, while suppression of NK cells reduces their cytotoxic activity. Activated macrophages also decreases IL-6, IL-13, IL-23 and IL-1β that further blocks the activation of CD4+cells and subsequent stimulation of Th1, Treg and Th17 cells. SARS-Cov-2 = severe acute respiratory syndrome coronavirus 2; NET = neutrophil extracellular trap; ROS = reactive oxygen species; IFN-γ = interferon-gamma; Th = T-helper cells; DC = dendritic cells; CD4+= cluster of differentiation 4; Treg = regulatory T-cells; T-cells = T-lymphocytes; B-cells = B-lymphocytes; IL = interleukin; TNF-α = tumour necrosis factor alpha; NK = natural killer; CD8+ = cluster of differentiation 8.