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Targeting the Imbalanced Immune Response in COVID-19
Too much histamine or prostaglandin D2 signaling or too little interferon signaling lead to increased risk for severe COVID-19.
An imbalanced immune response appears to be the key to whether a person develops severe COVID-19 with pneumonia and other complications such as coagulopathy (excessive formation of blood clots), impaired kidney function, neurological issues, and heart complications. Multiple mechanisms likely contribute to the variability in the immune response within the population and determine whether a person has asymptomatic disease, mild disease, or severe disease with potentially fatal complications. Increased understanding of the immune response to infection by the SARS-CoV-2 response will enable clinicians to provide optimal treatment to rebalance the response, either preventing people infected with the virus from developing a serious case of COVID-19 or providing appropriate effective treatment if someone does.
Here, I focus on three of these: An impaired interferon response, an excessive mast cell response, and excess signaling through a specific prostaglandin receptor.
Ineffective interferon response
An ineffective early interferon type I response is one path that leads to severe COVID-19. Interferons are a family of proteins that provide the first response to control viral infections, engaging immune cells to kill the virus and inducing pathways that enable the immune system to identify and eliminate infected cells to control the spread of the virus.
Genetic studies identified mutations in genes in this interferon pathway that impair this critical antiviral response, leading to severe COVID-19. Eventually a genetic test that includes the mutations so far identified (and likely others yet to be identified) may become available to screen for COVID-19 susceptibility and design the optimal treatment and prioritize vaccination of those people at increased risk.
