The research, published in the Journal of Medical Virology, shows that an interaction between the body's two main lines of defence may be causing the immune system to go into overdrive in some patients.
The body's first line of defence, the innate immune response, starts right after an infection, killing the virus and any cells damaged by it, said researchers from the University of Southern California (USC) in the US.
The second line of defence, the adaptive immune response, kicks in days later if any virus remains, employing what it has learned about the virus to mobilise a variety of special forces such as T cells and B cells, they said.
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.
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 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, they said.
However, 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 modelling 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.
"The danger is, as the infection keeps going on, it will mobilise the whole of the adaptive immune response with its multiple layers," said Weiming Yuan, an associate professor at USC.
"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," Yuan said.
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.
"Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms," said Sean Du, lead author of the study.
"It's possible that the combined effect of the adaptive and the innate immune responses may reduce the virus to a low level temporarily.
"However, if the virus is not completely cleared, and the target cells regenerate, the virus can take hold again and reach another peak," Du said.
Based on the results of the mathematical modeling, the researchers propose 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, we 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," Du explained. SARSAR