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The body’s first line of defense, the innate immune response, begins right after an infection, killing the virus and the cells damaged by it, researchers at the University of Southern California (USC) in the United States said.
The second line of defense, the adaptive immune response, is activated days later if a virus remains, using what it has learned about the virus to mobilize a variety of special forces such as T cells and B cells, they said.
Using the “target limited cell model,” a common mathematical model developed to understand the dynamics of viral infections, the researchers examined how the two immune responses work in patients with Covid-19 compared to patients who have the flu.
The researchers noted that the flu is a fast-moving infection that attacks certain target cells on the surface of the upper respiratory system and kills almost all target cells in 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 eliminate almost all of the virus from the body before the adaptive system comes into play, they said.
However, Covid-19, which targets surface cells throughout the respiratory system, including the lungs, has an average incubation of six days and much slower disease progression.
The mathematical model suggests that the adaptive immune response may be activated before target cells are depleted, slowing down the rate of infection and interfering with the ability of the innate immune response to kill most of the virus quickly.
“The danger is that, as the infection continues, it will mobilize the entire adaptive immune response with its multiple layers,” said Weiming Yuan, an associate professor at USC.
“This increased duration of viral activity can lead to an overreaction of the immune system called a cytokine storm, which kills healthy cells and causes tissue damage,” Yuan said.
The interaction of innate and adaptive immune responses may also explain why some Covid-19 patients experience two waves of the disease, which appear to improve before worsening.
“Some Covid-19 patients may experience a resurgence of the disease after an apparent decrease in symptoms,” said Sean Du, lead author of the study.
“It is possible that the combined effect of innate and adaptive immune responses temporarily reduces the virus to a low level.
“However, if the virus is not completely eliminated and the target cells regenerate, the virus can take over again and reach another peak,” Du said.
Based on the results of mathematical modeling, the researchers propose that a short regimen of a suitable immunosuppressive drug applied early in the disease process can improve patient outcome.
“With the right suppressive agent, we can delay the adaptive immune response and prevent it from interfering with the innate immune response that allows for faster clearance of the virus and infected cells,” Du explained.