In a new study, researchers found that temporarily suppressing the body’s immune system during the early stages of COVID-19 could help a patient avoid severe symptoms.
They showed that an interaction between the body’s two main lines of defense may be causing the immune system to go into overdrive in some patients.
The research was conducted by a team at USC.
The body’s first line of defense, the innate immune response, starts right after infection, like an infantry going after a foreign invader, killing the virus and any cells damaged by it.
The second line of defense, the adaptive immune response, kicks in days later if any virus remains, employing what it has learned about the virus to mobilize a variety of special forces such as T cells and B cells.
Using the “target cell-limited model,” a common mathematical model developed to understand the dynamics of viral infections, the researchers examined how the two immune responses work in COVID-19 patients compared to patients who have the flu.
The flu is a fast-moving infection that attacks certain target cells on the surface of the upper respiratory system and kills almost all of the target cells within two to three days.
The death of these cells deprives the virus of more targets to infect and allows the innate immune response time to clear the body of almost all of the virus before the adaptive system comes into play.
But COVID-19, which targets surface cells throughout the respiratory system including in the lungs, has an average incubation of six days and a much slower disease progression.
Mathematical modeling suggests that the adaptive immune response may kick in before the target cells are depleted, slowing down the infection and interfering with the innate immune response’s ability to kill off most of the virus quickly.
But the danger is, as the infection keeps going on, it will mobilize the whole of the adaptive immune response with its multiple layers.
This longer duration of viral activity may lead to an overreaction of the immune system, called a cytokine storm, which kills healthy cells, causing tissue damage.
The interaction of the innate and the adaptive immune responses might also explain why some COVID-19 patients experience two waves of the disease, appearing to get better before eventually getting much worse.
The most provocative result of the research is the kind of treatment it suggests to prevent this interaction between the two immune responses.
The team proposed a counterintuitive idea that a short regimen of a proper immunosuppressant drug applied early in the disease process may improve a patient’s outcome
With the right suppressive agent, doctors may be able to delay the adaptive immune response and prevent it from interfering with the innate immune response, which enables faster elimination of the virus and the infected cells.
Small studies out of China, including a recent one of COVID-19 patients and one of SARS patients in 2003 show patients who received immunosuppressants such as corticosteroids had better results than those who did not.
The researchers said a possible next step could be to take daily measurements of viral loads and other biomarkers in COVID-19 patients, to see if the data validates the mathematical modeling.
More preclinical studies including experiments in animal models will also be needed to prove the efficacy of an early immune-suppressing treatment.
The lead author of the study is Weiming Yuan, an associate professor in the Department of Molecular Microbiology and Immunology.
The study is published in the Journal of Medical Virology.
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