In a new study from USC, experts have found that the timing of the immune response may play a major role in the progression of COVID-19. The research suggests that suppressing the body’s immune system during the early stages of infection may be the best route to control the severity of the disease.
According to the study, the interaction between the innate and the adaptive immune responses to COVID-19 may be pushing the immune system into overdrive.
Study co-author Weiming Yuan is an associate professor in the Department of Molecular Microbiology and Immunology at the USC Keck School of Medicine . and co-corresponding author of the study.
“The danger is, as the infection keeps going on, it will mobilize the whole of the adaptive immune response with its multiple layers,” said Professor Yuan.
“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 innate immune response is the body’s first line of defense. This system sets out to kill a virus and any cells that are damaged at the very first sign of infection. The adaptive immune response is activated days after the initial infection, using what it has learned about the virus to deploy specific T cells and B cells.
The researchers used a mathematical model to compare how the two immune responses interact in COVID-19 and flu patients.
The flu moves very fast, attacking certain target cells on the surface of the upper respiratory system that can be wiped out in a matter of two or three days. The virus runs out of target cells quickly, and the innate immune system can wipe out the virus before the adaptive system is activated.
COVID-19 targets more surface cells throughout the respiratory system, including cells in the lungs, and progresses much more slowly than the flu. The model indicated that the adaptive immune response kicks in before the target cells are depleted. This interferes with the innate immune system’s ability to wipe out the virus quickly.
The interaction of the innate and the adaptive immune responses may explain why some patients have two waves of the illness. COVID-19 patients often show signs of improvement before getting much worse.
“Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms,” said study lead author Sean Du. “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.”
A treatment to suppress the immune system in the early phase of COVID-19 infection may seem counterintuitive, but the research suggests it would be effective.
“Based on the results of the mathematical modeling, we 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,” said Du.
“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.”
Small studies from China, involving both COVID-19 and SARS patients, showed that individuals who received immunosuppressants such as corticosteroids had better outcomes.
According to the researchers, 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.
The study is published in the Journal of Medical Virology.