Many COVID-19 patients are severe enough to warrant admission to the hospital for monitoring and treatment.
A lot of these patients die from the disease after appearing to respond well to treatment.
The major cause of these deaths is the ‘cytokine storm’, which happens when hyper-activation of immune cells leads to a large number of cytokines (cell signaling molecules), which in turn trigger systemic hyper-inflammation.
If untreated, this leads to multiple organ failure and death.
If the ‘cytokine storm’ could be prevented, the deaths due to this phenomenon would drastically decrease, reducing the overall death rate in COVID-19.
In a recent study at Hokkaido University, researchers reviewed the existing research on macrophage activation syndrome (MAS).
They found the role MAS plays in COVID-19 and how existing therapies could help treat severe COVID-19.
The study is published in the journal Inflammation and Regeneration. One author is Ryo Otsuka.
The cytokine storm occurs in other diseases such as influenza, pneumonia, and sepsis, and has been studied in some detail.
Along with MAS, an associated syndrome is the Acute Respiratory Distress Syndrome (ARDS), which has a rapid onset of widespread inflammation in the lungs—a common feature of severe COVID-19 cases.
Thus, the scientists reviewed the links between MAS and ARDS and the role MAS played in COVID-19.
They found that MAS in COVID-19 was accompanied by ARDS and that far more cytokines were involved than in previously documented cases of MAS.
This difference is caused by the SARS-CoV-2 virus. When the virus enters the cells, it triggers an inflammatory response as the cells fight against it.
The virus also triggers the inflammatory response by causing pyroptosis (a type of cell death caused when it infects cells), which activates macrophages.
The activated macrophages recruit T cells, which activate more macrophages, triggering a positive feedback loop.
This causes MAS, which in turn leads to ARDS—which, untreated, is fatal.
According to the team, MAS is directly triggered by cytokines such as interleukin-6 (IL-6) and Tumor Necrosis Factor α (TNFα), and indirectly by IL-1.
Previous studies had used therapies targeting these molecules to suppress MAS. These therapies show promise in reducing the severity of COVID-19.
Studies have been carried out on tocilizumab (an IL-6 blocker) for severe cases in China, and on anakinra (an anti-IL-1 medication) for non-severe cases in Italy, and the results are generally positive.
Additionally, in a trial conducted on 19 patients in the U.S., treatment with acalabrutinib, a drug that targets the production of IL-1, also had favorable outcomes in severe COVID-19 cases.
There are currently many clinical trials underway, testing many drugs that act on different aspects and stages of infection by SARS-CoV-2.
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