TB and COVID-19 coinfection: Investigating the clinical and biological interactions between Mycobacterium tuberculosis and SARS-CoV-2

The novel SARS-CoV-2 and ancient Mycobacterium tuberculosis (M.tb) represent a collision of the public health emergencies and coinfection with these infectious pathogens could have disastrous consequences for the UK and internationally.

There is significant potential for COVID-19 to superimpose on M.tb infections, resulting in coinfections that co-exacerbate. This may potentially be more important in indolent, latent tuberculosis infections (LTBI), which are typically well-controlled by active, ongoing immunity. For instance, SARS-CoV-2 causes marked lymphopenia in symptomatic COVID-19 disease.

Since antigen-specific T-cell responses are crucial for the control of M.tb and in LTBI diagnostics, this may have serious sequelae. Moreover, preliminary studies suggest that TB infection and disease increase susceptibility and disease severity in COVID-19. However, this relationship is poorly characterised - naturally, there is currently more opinion in the literature than data.

There are no data about the influence of SARS-CoV-2 on the progression of LTBI to active TB (ATB) and no experimental data surrounding immunopathological aspects of M.tb and SARS-CoV-2 coinfection. To answer these unknowns we will address the following hypothesis and objectives:

Hypothesis "SARS-CoV-2 infection impairs immune control of M.tb, leading to progression of LTBI to ATB, confounding LTBI diagnostics and limiting TB control programme delivery" Objectives: 1. To determine the effects of SARS-CoV-2 on immune control of M.tb in TB infection, disease and diagnostics

2. To study the incidence of COVID-19 among patients with ATB and LTBI, and its impact on disease severity and provision of TB control services