COVID-19 could accelerate activation of dormant tuberculosis (TB)

COVID-19 could accelerate activation of dormant tuberculosis (TB)

The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has thrown much of the world into disarray, with over 4 million people reported infected and well over 282,000 deaths. A new study published on the preprint server bioRxiv * in May 2020 suggests that the long-term impact of the virus could include activation of dormant bacterial infections like tuberculosis (TB). According to the World Health Organization (WHO), dormant TB already affects a quarter of the world’s population. If the novel coronavirus activates a sizable proportion of these dormant infections, it could severely upset the global health and economic situation. The current study aims at quantifying this association so as to shape policies that could help avert a global TB pandemic. Many viruses, including SARS-CoV-2, cause a temporary immunosuppressive effect, which causes dormant bacterial infections to come back to life. This was the case with the Spanish flu pandemic of 1918-20, which caused an increase in the number of lung TB cases. The highest death rate was in the patient subgroup, which had influenza with TB. The 2009 HIN1 flu pandemic also showed the same trend, with poorer outcomes in patients coinfected with TB or multidrug-resistant strains of TB (MDR-TB). Patients with SARS or MERS infections were also found to develop lung TB. The researchers in the current study hypothesized that the CoV infections could be causing lung inflammation that leads to reactivation of dormant TB in the lung. Others say that both lung lesions and liver infection by the mycobacteria, which cause TB ( Mycobacterium tuberculosis , MTB) are enhanced by the presence of influenza A in mouse models, which also show a type I interferon signaling pathway that increases mycobacterial growth. Study: Coronavirus activates a stem cell-mediated defense mechanism that accelerates activation of dormant tuberculosis: implications for the COVID-19 pandemic . Image Credit: Tatiana Shepeleva / Shutterstock The current study focuses on dormant TB in adult stem cells. These cells may live in the bone marrow as well as in inflamed areas. One subset, called CD271+BM-mesenchymal stem cells (CD271+BM-MSCs), could harbor the dormant mycobacteria in both mice and humans, allowing later reactivation. In prior studies, the investigators developed a mouse model that shows how the stem cells mediate this phenomenon. Mice are infected with the mycobacteria and show granuloma formation as well as antibodies to these organisms, after being treated with streptomycin for 3 weeks. When they are later deprived of streptomycin for six months, the bacteria become non-replicating. The MTB are found mostly within the CD271+MSCs of the bone marrow and the lung to a much lesser extent. Those in the bone marrow live under relatively hypoxic conditions. It is known that the ability to culture MTB from non-CD271+MSCs in the lungs of these mice signal tuberculous reactivation, which makes this model useful in the study of stem cell-mediated MTB reactivation. The researchers looked for proof of dormant MTB reactivation using a murine hepatitis virus strain-1 (MHV-1), which is a murine coronavirus capable of representing the clinical features of SARS-CoV-2 in humans. MHV-1 induces acute respiratory infection in 2-4 days of infection, which leads to acute lung inflammation, with high levels of inflammatory chemicals like TNF-alpha, within 2-14 days of infection, and then recover. An in vitro study showed the susceptibility of type II alveolar epithelial cells to MHV-1, which allows the use of these cells to identify an antiviral defense mechanism mediated by these altruistic stem cells (ASC). The study shows the activation of the ASC-associated innate defense mechanism on MHV-1 infection. This mechanism has previously been found in embryonic stem cells (ESCs). MHV-1 may activate these specialized defense mechanisms within MTB-positive stem cells, leading to increased MTB proliferation in the lung and thus reducing the viral load. The researchers also observed an unexpected finding: MTB reactivation is linked to an increase in the number of lung cells in the vicinity that survive, leading to an interest in the possible therapeutic application of this defense mechanism. Did the MHV-1 infection cause MTB reactivation? The researchers administered MHV-1 intranasally to mice with dormant MTB in these stem cells, along with streptomycin, which is required for this strain of MTB to replicate. They found that in both test and control groups, the viral titer increased rapidly over the first four weeks but then went down. However, the viral load after two weeks was 20 times less in the test than in control mice. In both groups, the TNF-alpha levels went up by 3-4 times. These results suggest that viral replication and immune activation occurred in both groups, but the viral load was less in the mice with dormant MTB infection. Related Stories



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