TB and COVID-19 coinfection: Investigating the clinical and biological interactions between Mycobacterium tuberculosis and SARS-CoV-2
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Immunology & Immunotherapy
Abstract
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
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
Technical Summary
UKRI priority areas include understanding the interaction between SARS-CoV-2 and other pathogens. M.tb and SARS-CoV-2 have significant potential to interact and therefore impact on clinical outcomes.
The two major knowledge gaps to be addressed by this project are:
1. The reciprocal biological impact of SARS-CoV-2 and M.tb on immunity to each other
2. How the pandemic has affected outcomes and the provision of TB services
Research to date has focussed on retrospective studies exploring relationships between TB and COVID-19 and suggest M.tb increases susceptibility to SARS-CoV-2 and disease severity. The control of LTBI requires the maintenance of effective T-cell responses. When these are perturbed (e.g. HIV infection, anti-TNF treatment), the risk of reactivation increases significantly. SARS-CoV- 2 infections may cause lymphopenia and the impact of this on M.tb-specific T-cell response is unknown, nor is it clear if these return to normal levels. One reason for the lack of understanding of the relationship between these pathogens is the limited availability of sufficiently-sized populations of M.tb-infected patients and the clinical infrastructure to assess them. The assembled team has the appropriate expertise to address these issues and the cohorts of patients within a single joined-up health region.
The two major knowledge gaps to be addressed by this project are:
1. The reciprocal biological impact of SARS-CoV-2 and M.tb on immunity to each other
2. How the pandemic has affected outcomes and the provision of TB services
Research to date has focussed on retrospective studies exploring relationships between TB and COVID-19 and suggest M.tb increases susceptibility to SARS-CoV-2 and disease severity. The control of LTBI requires the maintenance of effective T-cell responses. When these are perturbed (e.g. HIV infection, anti-TNF treatment), the risk of reactivation increases significantly. SARS-CoV- 2 infections may cause lymphopenia and the impact of this on M.tb-specific T-cell response is unknown, nor is it clear if these return to normal levels. One reason for the lack of understanding of the relationship between these pathogens is the limited availability of sufficiently-sized populations of M.tb-infected patients and the clinical infrastructure to assess them. The assembled team has the appropriate expertise to address these issues and the cohorts of patients within a single joined-up health region.
| Description | Analysis of a large dataset of individuals with different types of TB and COVID has shown that a history of previous latent TB infection is associated with a lower chance of being admitted to hospital with severe COVID-19. Laboratory studies using cells collected from individuals before the pandemic with latent TB has shown that when these are stimulated with COVID-19 they produce an immune reaction. We are still studying this to try to understand what the underlying reasons for this might be. Finally, there is a small group of people with COVID-19 who, when their blood is incubated with TB in the lab, they are worse at controlling TB growth than other people. This seems to be related to a differences in some key immune cells. Taken together, these findings highlight that TB and COVID-19 interact in different ways depending on the time of exposure, which could be very important in understanding how to manage these infections. |
| Exploitation Route | We are now testing whether previous exposure to mycobacteria (latent TB) might re-train the innate immune system to provide protection against different infections (such as COVID-19). These could have widespread implications in healthcare settings. |
| Sectors | Healthcare |
| Description | Academic collaboration. |
| Organisation | University of Birmingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have initiated a collaboration with Prof Jo Parish at the University of Birmingham to undertake further work following some of our findings. |
| Collaborator Contribution | Expertise in lab techniques testing trained immunity. |
| Impact | Too early to comment. |
| Start Year | 2023 |