The SARS-CoV-2 virus that causes COVID-19 may have the ability to reactivate
dormant tuberculosis (TB). In a novel study scientists report in The
American Journal of Pathology that infection with a specific coronavirus
strain reactivated dormant Mycobacterium tuberculosis (MTB) in mice. This
knowledge may help to develop new vaccines for COVID-19 and avoid a
potential global tuberculosis epidemic.
The COVID-19 pandemic caused by the SARS-CoV-2 virus demonstrates the
ability of an emerging virus to affect masses and strain and disrupt the
workings of modern healthcare systems around the world. A significant number
of infected COVID-19 individuals have recovered. However, a possible host
defense or antiviral mechanism against the virus is yet to be identified.
There are concerns that in the long-term, the virus might activate dormant
bacterial infections such as TB in select infected individuals, as
alarmingly, TB is already present in one quarter of the world population.
Viral infections such as the influenza virus or SARS-CoV-1 are known to
cause transient immune suppression that leads to reactivation of dormant
bacterial infection. The highest death rate during the Spanish flu pandemic
of 1918 was in patients with TB, and patients with TB or multidrug-resistant
TB had a worse prognosis than others during the influenza A (H1N1) pandemic
in 2009.
"There is an urgent need to study the association of COVID-19 with dormant
TB reactivation to avoid a potential global TB pandemic," explained lead
investigator Bikul Das, MD, PhD, Department of Stem Cell and Infectious
Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of
Technology, Guwahati, India; and Department of Stem Cell and Infection,
Thoreau Lab for Global Health, University of Massachusetts, Lowell, MA, USA.
"It is important to understand the host defense mechanism against this
disease to develop a better vaccine and/or treatment. We therefore
postulated that, similar to bacteria, adult stem cells may also exhibit an
altruistic defense mechanism to protect their niche against external
threat."
Investigators studied the coronavirus strain murine hepatitis virus-1
(MHV-1) infection in the lung in a mouse model (dMtb) of mesenchymal stem
cell (MSC)-mediated MTB dormancy. This showed 20-fold lower viral loads than
the dMtb-free control mice by the third week of viral infection and a
six-fold increase of altruistic stem cells (ASCs), thereby enhancing the
defense. Tuberculosis was reactivated in the dMtb mice, suggesting that
dormant TB bacteria hijack these ASCs to replicate in the lung to cause
pulmonary TB. Results suggest that these ASCs are transient (they expand for
two weeks and then undergo apoptosis or cellular suicide) and exhibit
antiviral activities against MHV-1 by secreting soluble factors.
"These findings are important because they reveal a novel ASC defense
mechanism against mouse coronavirus infection, which could be used to
develop novel therapeutic approaches against COVID-19," noted Bikul Das.
"The finding of TB reactivation in a stem cell-mediated Mtb dormancy mouse
model during MHV-1 coronavirus infection indicates that in the long-term,
post-pandemic, the SARS-CoV-2 virus might activate dormant bacterial
infections. This is a significant finding considering the current
coronavirus pandemic, where many individuals in India and other developing
countries with dormant TB infection may see an increase in active TB cases
post COVID-19. The ASC-mediated defense mechanism may be targeted to develop
vaccines against viral infections and avoid a potential global TB pandemic."
Reference:
Pathak L, Gayan S, Pal B, et al. Coronavirus activates an altruistic stem
cell–mediated defense mechanism that reactivates dormant tuberculosis:
implications in coronavirus disease 2019 pandemic. Am J Pathol. 2021;0(0).
doi:
10.1016/j.ajpath.2021.03.011