In a new study, researchers suggest a possible mechanism that causes a massive release of proinflammatory cytokines, or a cytokine storm, leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients.
The results are based on recent findings that explain how SARS-CoV-2 enters human cells.
The research was conducted by a team at Hokkaido University and elsewhere in Japan.
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, which leads to ARDS.
In the study, the team reviewed previous findings to find effective therapeutic strategies for ARDS in COVID-19 patients.
They suggest that SARS-CoV-2 enters human cells by attaching to a cell surface receptor called ACE2 and utilizing a human enzyme called TMPRSS2.
Drugs that block the ACE2 receptor or that inhibit the enzyme could help treat the initial stages of the disease.
However, ARDS with cytokine storm starts to appear in the later phase of infection even when the number of virus decreases. So, there must be another pathway that causes the cytokine storm.
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.
Angiotensin II triggers an inflammatory pathway in nonimmune cells. This pathway forms a positive feedback cycle, resulting in its excessive activation and therefore the cytokine storm and ARDS.
Part of this pathway 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.
The team says that 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.
The lead author of the study is Masaaki Murakami, the head of the immunology laboratory.
The study is published in Immunity.
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