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Covid-19: Keck School of Medicine’s Novel Therapy Is Promising

New research suggests that the interaction between the innate and adaptive immune responses may contribute to the severity of the SARS-CoV-2 disease

Coronavirus. Photo: U.S. Army

Scientists from the Keck School of Medicine at USC investigated whether and how the timing in the interactions between the body’s two main lines of defense against pathogens during infection, innate and adaptive immune responses, may contribute to the severity of the COVID-19 disease. They used a mathematical modeling system, known as the “target cell-limited model”, which represents a useful tool to understand the dynamics of viral infections. The model was first validated when applied to the well-known pathogenesis processes of the influenza virus, and then it was applied to the SARS-CoV-2 virus.

We know that, right after an infection, our body activates sequential orders of responses to remove the pathogen. Innate immunity is immediate upon contact with the infectious agent, acts through constant mechanisms, and tends to kill the virus and the cells that it damaged, to avoid the onset of infection. The adaptive immune response happens days later, and it is necessary against those pathogens that escape the innate response. It requires some time to activate immune cells, such as B and T lymphocytes, which act selectively against a specific pathogen.

When the flu virus infects the target cells in the upper respiratory system, it kills almost all of them within two or three days, allowing time for the innate immune response to clear the body of almost all of the virus. Thus, the adaptive response finishes the fight against the remaining viral particles. The incubation time for SARS-CoV-2 is longer, approximately six days, and the virus affects the whole respiratory system, lungs included, and induces a slower progression of the disease.

According to the model, it seems that the adaptive immune response steps in before the infected cells can be totally depleted by the innate immune response. This timing mismatch implies that, while the infection progresses, the adaptive immune system response is activated, and it may overreact and lead to the so-called “cytokine storm”, which ultimately involves a sustained inflammatory state that kills healthy cells as well and causes tissue damage.

This could explain why Covid-19 has such a severe outcome in some of the affected patients, and is lethal in some cases. It could also explain why some patients experience an initial improvement clinically, that eventually gets much worse; the virus level may initially decrease, but if it is not completely removed, the infected cells may regenerate, allowing the virus to peak again. These discoveries, funded by the National Institute of Allergy and Infectious Diseases, and partially by an NIH fund, have just been published in the Journal of Medical Virology, and suggest another way to combat SARS-CoV-2, which could potentially prove significant in the fight against this disease: the use of a proper immunosuppressant regimen in the earlier phases of the disease, with the purpose of delaying the adaptive immune response, and preventing its interaction with the innate response. While this idea is intriguing, many pre-clinical studies are still needed before its application can be proven effective.

 

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