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COVID-19 may lead to spate in TB cases

By Rituraj Borthakur
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GUWAHATI, May 16 - The spread of novel coronavirus in the country may trigger a spate in tuberculosis cases, with a research indicating that COVID 19 can reactivate dormant tuberculosis cells.

A team of researchers at KaviKrishna Laboratory in Guwahati led by its director Dr Bikul Das has demonstrated a unique stem cell-based defense mechanism against coronavirus infection which suggests that coronavirus infection may reactivate the dormant Mycobacterium tuberculosis (dMtb).

History has it that tuberculosis is one of the key bacterial infections affected by viral pandemics. In 1918, the Spanish Flu pandemic led to the rise of pulmonary tuberculosis (TB) incidence. Influenza in patients with TB had the highest death rate. In the year 2009 during the influenza A (H1N1) pandemic, a worse prognosis of influenza was observed in patients with TB or MDR (multi-drug resistant)/TB.

Every year nearly 10 million new TB cases are reported, according to the World Health Organization. India is the leading country of TB burden, where two third of the total population is infected. Strikingly, one quarter of the world population is already infected with dormant TB and 40 per cent of Indian population is infected with dormant TB.

�If SARS-CoV-2, which is the causative agent of COVID-19, infects these dormant TB populations, it may cause severe impact in global health and economics by causing both COVID-19 and dormant TB reactivation,� Dr Das, the principal investigator of this research study, said.

�In 2013, our lab found that Mtb remains dormant inside the bone marrow mesenchymal stem cells (BM-MSCs) for decades in humans, who were successfully cured with treatment for TB. Using a mice model, we also showed that these dormant Mtb has the potential for future reactivation. Further, we have demonstrated that these dormant Mtb harbouring BM-MSCs resides in the hypoxic niche and this stem cell niche acts as an antibiotic protective niche for the Mtb. These findings provide a new direction in the field of TB translational research, but we are not clear how the bacteria escape from stem cells to reactivate the disease in the lung.

Hence, for the last few years, we were using a mouse coronavirus mediated lung infection to study whether viral infection causes the bacteria to escape from stem cells,� Dr Das said.

A mouse coronavirus strain � the murine hepatitis virus-1 (MHV-1) � that represents clinically relevant human coronavirus SARS-CoV-1 infection was used in the research. The remarkable significance of the study is that although MHV-1 infection causes dMtb reactivation, it also activates an altruistic stem cell (ASC)-based innate defence mechanism against the virus.

The lab has been a pioneer in ASC-based research. Now that MHV-1 has been found to activate ASC defence, this mechanism could be further explored to develop therapeutics to target corona virus.

�In plain words, it can be explained that though the virus will reactivate the TB, it will also set off the defence mechanism against the virus and ultimately defeat it, in most cases, and further study of this defence mechanism could help in treatment of the virus,� Das said.

He also cited recent surveys and reports that countries which do not have a policy of universal Bacille Calmette Guerin (BCG) vaccination, which is closely related to Mtb, have experienced higher mortality related to COVID 19.

�Thus our results could provide a novel explanation of BCG mediated host defence or anti-viral mechanism against SARS-CoV-2 that could be further utilized to design a drug or vaccine against the virus,� he said.

The research team included Lekhika Pathak, Sukanya Gayan, Bidisha Pal, Joyeeta Talukdar, Seema Bhuyan, Sorra Sandhya, Herman Yeger, Debabrat Baishya, besides Dr Bikul Das

Dr Das and his research team has published their findings in a paper � �Corona virus activates a stem cell mediated defense mechanism that accelerates activation of dormant tuberculosis: implications for the COVID-19 pandemic� � on pre-print server bioRxiv recently. However, these are preliminary findings and await peer-review.

Now, the laboratory is actively pursuing research to confirm the findings in human subjects. Importantly, the laboratory is also testing the efficacy of the BCG stem cell vaccine against coronavirus using mouse model of coronavirus. Previously, the lab has developed the BCG stem cell vaccine against cancer.

KaviKrishna Laboratory is a division of KaviKrishna, a research-based NGO committed to research on stem cell altruism to India.

In the year 2018, KaviKrishna received the recognition of scientific and industrial research organisation (SIRO), which has been a remarkable achievement for the organisation in its 8 yearlong journey. Along with the SIRO certification, KaviKrishna was able to form �Institutional Committee for Stem Cell Research (ICSCR)� and become the first organisation of having ICSCR in North East India.

The laboratory is now actively engaged in cutting-edge research on stem cell altruism in collaboration with its sister laboratory, The Thoreau Laboratory of Global Health at University of Massachusetts � Lowell, MA, managed by KaviKrishna USA Foundation.

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COVID-19 may lead to spate in TB cases

GUWAHATI, May 16 - The spread of novel coronavirus in the country may trigger a spate in tuberculosis cases, with a research indicating that COVID 19 can reactivate dormant tuberculosis cells.

A team of researchers at KaviKrishna Laboratory in Guwahati led by its director Dr Bikul Das has demonstrated a unique stem cell-based defense mechanism against coronavirus infection which suggests that coronavirus infection may reactivate the dormant Mycobacterium tuberculosis (dMtb).

History has it that tuberculosis is one of the key bacterial infections affected by viral pandemics. In 1918, the Spanish Flu pandemic led to the rise of pulmonary tuberculosis (TB) incidence. Influenza in patients with TB had the highest death rate. In the year 2009 during the influenza A (H1N1) pandemic, a worse prognosis of influenza was observed in patients with TB or MDR (multi-drug resistant)/TB.

Every year nearly 10 million new TB cases are reported, according to the World Health Organization. India is the leading country of TB burden, where two third of the total population is infected. Strikingly, one quarter of the world population is already infected with dormant TB and 40 per cent of Indian population is infected with dormant TB.

�If SARS-CoV-2, which is the causative agent of COVID-19, infects these dormant TB populations, it may cause severe impact in global health and economics by causing both COVID-19 and dormant TB reactivation,� Dr Das, the principal investigator of this research study, said.

�In 2013, our lab found that Mtb remains dormant inside the bone marrow mesenchymal stem cells (BM-MSCs) for decades in humans, who were successfully cured with treatment for TB. Using a mice model, we also showed that these dormant Mtb has the potential for future reactivation. Further, we have demonstrated that these dormant Mtb harbouring BM-MSCs resides in the hypoxic niche and this stem cell niche acts as an antibiotic protective niche for the Mtb. These findings provide a new direction in the field of TB translational research, but we are not clear how the bacteria escape from stem cells to reactivate the disease in the lung.

Hence, for the last few years, we were using a mouse coronavirus mediated lung infection to study whether viral infection causes the bacteria to escape from stem cells,� Dr Das said.

A mouse coronavirus strain � the murine hepatitis virus-1 (MHV-1) � that represents clinically relevant human coronavirus SARS-CoV-1 infection was used in the research. The remarkable significance of the study is that although MHV-1 infection causes dMtb reactivation, it also activates an altruistic stem cell (ASC)-based innate defence mechanism against the virus.

The lab has been a pioneer in ASC-based research. Now that MHV-1 has been found to activate ASC defence, this mechanism could be further explored to develop therapeutics to target corona virus.

�In plain words, it can be explained that though the virus will reactivate the TB, it will also set off the defence mechanism against the virus and ultimately defeat it, in most cases, and further study of this defence mechanism could help in treatment of the virus,� Das said.

He also cited recent surveys and reports that countries which do not have a policy of universal Bacille Calmette Guerin (BCG) vaccination, which is closely related to Mtb, have experienced higher mortality related to COVID 19.

�Thus our results could provide a novel explanation of BCG mediated host defence or anti-viral mechanism against SARS-CoV-2 that could be further utilized to design a drug or vaccine against the virus,� he said.

The research team included Lekhika Pathak, Sukanya Gayan, Bidisha Pal, Joyeeta Talukdar, Seema Bhuyan, Sorra Sandhya, Herman Yeger, Debabrat Baishya, besides Dr Bikul Das

Dr Das and his research team has published their findings in a paper � �Corona virus activates a stem cell mediated defense mechanism that accelerates activation of dormant tuberculosis: implications for the COVID-19 pandemic� � on pre-print server bioRxiv recently. However, these are preliminary findings and await peer-review.

Now, the laboratory is actively pursuing research to confirm the findings in human subjects. Importantly, the laboratory is also testing the efficacy of the BCG stem cell vaccine against coronavirus using mouse model of coronavirus. Previously, the lab has developed the BCG stem cell vaccine against cancer.

KaviKrishna Laboratory is a division of KaviKrishna, a research-based NGO committed to research on stem cell altruism to India.

In the year 2018, KaviKrishna received the recognition of scientific and industrial research organisation (SIRO), which has been a remarkable achievement for the organisation in its 8 yearlong journey. Along with the SIRO certification, KaviKrishna was able to form �Institutional Committee for Stem Cell Research (ICSCR)� and become the first organisation of having ICSCR in North East India.

The laboratory is now actively engaged in cutting-edge research on stem cell altruism in collaboration with its sister laboratory, The Thoreau Laboratory of Global Health at University of Massachusetts � Lowell, MA, managed by KaviKrishna USA Foundation.

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