Immunologists in Japan propose that massive release of proinflammatory cytokines lead to the development of COVID-19 in patients.
Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition in which lungs become so inflamed and filled with fluid that they struggle to provide enough oxygen to the body. "To rescue the patients from this condition, it is vital to understand how SARS-CoV-2 triggers the cytokine storm, that leads to ARDS," explains Masaaki Murakami, the head of immunology laboratory at Hokkaido University's Institute for Genetic Medicine.
Murakami and Toshiro Hirano from the National institutes for Quantum and Radiological Science and Technology, reviewed two recent studies by Zhou et. al. and Hoffmann et. al. to gain understanding on the implications for finding effective therapeutic strategies for ARDS in COVID-19 patients.
The studies suggested that SARS-CoV-2 enters human cells by attaching to a cell surface receptor called ACE2 and utilizing a human enzyme called TMPRSS2. Murakami mentioned that drugs blocking the ACE2 reception or inhibit this enzyme provide potential for treatment of the initial stages of COVID-19.
SARS-CoV-2 is known to be engulfed into the human cell along with the ACE2 receptor it had combined with. "This reduces the number of ACE2 receptors on cells, leading to an increase of a polypeptide, called angiotensin II, in the blood," says Murakami. Angiotensin II triggers an inflammatory pathway involving NF-魏B and IL-6-STAT3 particularly in nonimmune cells including endothelial cells and epithelial cells. "This pathway forms a positive feedback cycle, named IL-6 amplifier, resulting in its excessive activation and therefore the cytokine storm and ARDS," says Hirano, a pioneer in IL-6 research.
"Part of this pathway involving NF-魏B or IL-6-STAT3, or the both, is enhanced with age, which could be why older people are more at-risk of death following COVID-19 infection compared to other age groups," explains Murakami. "Targeting these pathways, such as with the anti-IL-6 receptor antibody called tocilizumab, could disrupt this life-threatening inflammatory reaction in COVID-19 patients," Hirano added.
Their suggestions were published in the journal, Immunity, based on the recent findings that explain the invasion of SARS-CoV-2 into human cells.