Yashoda Madaiah Hosakote, PhD

The ongoing devastating COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in overwhelming number of deaths worldwide and still rising. New variants of the virus continue to emerge, such as the recent Delta, Omicron and now its subvariants, which have crippled the world’s economy and weakened healthcare systems. SARS-CoV-2 infection induces an unwanted inflammatory response that can lead to lethal outcomes of COVID-19 disease. We have identified a protein called high mobility group box 1 (HMGB1), which alerts the immune system of potential damage that can be inflicted during SARS-CoV-2 infection. We will investigate the role of HMGB1 in SARS-CoV-2 infection, which may guide us on the development of novel therapeutic strategies to mitigate the COVID-19 pandemic.

Update:
Our studies demonstrated both the beneficial and the detrimental role of high mobility group box-1 (HMGB1) in promoting inflammation during SARS-CoV-2 infection. Our findings suggest that initial low levels of HMGB1 secretion are essential in alerting the immune system to tissue damage. However, excessive HMGB1 secretion promotes massive production of proinflammatory mediators called cytokines in immune cells, leading to uncontrolled inflammation and an impaired immune system. These findings suggest that modulation of HMGB1’s pro-inflammatory function could prevent acute and damaging inflammatory responses not only in COVID-19 patients but also for other emerging respiratory viral infections that affect the human population of all age groups.

Final Project Update: 
The recent COVID-19 pandemic caused by SARS-CoV-2 has led to a significant number of deaths worldwide and has greatly impacted the global economy. While the exact mechanisms of SARS-CoV-2 infection are still not fully understood, disease severity is believed to result not just from the replicating virus itself but also from the body's inflammatory response. Thus, managing this inflammatory response is as crucial as targeting the virus. 

Current data suggests that immune responses play a role in protecting against SARS-CoV-2 and in contributing to the severity of COVID-19. However, an overactive immune response can lead to excessive inflammation, which causes tissue damage and worsens the disease. Damage-associated molecular patterns (DAMPs) derived from the host contribute to these immune responses and can indicate disease progression and severity. One important DAMP is high mobility group box-1 (HMGB1), which promotes inflammation during infection or injury. 

While HMGB1 has been studied in various diseases, its specific role in COVID-19 is not well understood. In this study, we explored how HMGB1 release contributed to exacerbated inflammation during SARS-CoV-2 infection and provided evidence that it could serve as a valuable biomarker and therapeutic target for severe COVID-19.