15 May 2022
New research from the Royal Free London (RFL) has uncovered that some cells infected with COVID-19 can explode, leading to serious damage of the lungs and other internal organs.
The research, co-authored by RFL consultant hepatologist Gautam Mehta, shows that immune cells infected by COVID-19 can undergo a ‘cell explosion’ known as pyroptosis – and it’s this which causes the harmful inflammation in patients who become seriously unwell with the virus.
Although pyroptosis kills the virus, it also leads to inflammatory contents being released into the blood stream. These inflammatory contents travel around the body, damaging the lungs and other internal organs.
This same process can happen in liver patients where bacteria from the gut has infected the liver. In order to expel the bacteria, the liver cells undergo the same pyroptosis process - the cells explode and release inflammatory materials that harm surrounding cells.
These important findings will help researchers develop more effective treatments for COVID-19 in future.
The research, published in Nature last week, was a collaboration between Harvard Medical School in the US and Dr Mehta.
It follows on from work published by Dr Mehta’s team demonstrating that pyroptosis can lead to hyper-inflammation in liver disease.
Dr Mehta said: "During the early days of the pandemic, the emerging data suggested inflammation and cell death were both important factors in severe COVID-19. As it happened, the pyroptosis pathway of cell death, and its role in liver disease, was already an area of interest of our group.
“The pyroptosis pathway acts as an ‘alarm system’; if it senses bacterial or viral particles within the cell it leads to an ‘explosion’ of the cell and the release of pro-inflammatory contents. This has the benefit of eliminating the infection but can lead to severe inflammation as a result. Pyroptosis literally implies a ‘fiery’ mode of cell death.
"In liver disease patients, this occurs because of ‘leaky gut’, so bacterial components can reach the liver from the gut, and cause pyroptosis of liver cells leading to liver failure. In COVID-19, it seems this process also occurs because the virus triggers pyroptosis in immune cells, which has the benefit of eliminating the virus but can lead to hyper-inflammation in some people. It is this inflammation which can lead to acute respiratory distress and multi-organ damage.”
This work demonstrates not only the great power of collaborative networks of researchers, but also of patients to drive research advances in many fields.
Dr Mehta added: “The work describing pyroptosis in liver disease was driven by Royal Free Hospital patients who participated in the study. If it wasn’t for us studying this field at the time the pandemic hit, we may not have made the link between pyroptosis and COVID-19, which now has the potential to deliver targeted treatments for the condition.”