LOS ANGELES — A new research study out of the University of Southern California reveals how an irregular immune response to the COVID-19 infection can lead to some of the more severe symptoms seen in coronavirus patients.
Researchers used mathematical modeling to simulate the immune response to a coronavirus infection. They found that suppressing the immune system during the early stages of the infection might help patients avoid the severe symptoms.
When a person is infected with a virus the body deploys its first line of defense — the innate immune response. This stage of defense targets the virus and any cells damaged by the virus and kills off as much as it can. If there is any virus remaining after a few days the body calls on its adaptive immune response. This stage of defense uses special types of cells — T cells and B cells — to target and kill the rest of the virus and infected cells.
This strategy of immune response is typically very effective. When someone gets infected with the flu, the virus acts quickly to attack and destroy infected cells in the upper respiratory system. These cells are killed off within a couple of days, so the innate immune response focuses on clearing the body of any flu virus left in the body before the adaptive response is activated.
The time-course of COVID-19 makes this immune response strategy ineffective, and quite possibly counterproductive. The coronavirus has an incubation period of about 6 days, so the innate immune response does not have time to clear away the virus before the adaptive immune response is activated. This slows the progress of the disease, and the adaptive immune response is put into overdrive trying to fight the virus.
Professor Weiming Yuan, associate professor in the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, and co-corresponding author of the study comments on the risks of a hyperactive adaptive immune response, in a release. “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.”
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The authors suggest that the timing of the immune responses might also explain why some people infected with COVID-19 experience the disease in two separate waves.
“Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms,” says 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.”
The researchers use the results of their mathematical models to offer a new strategy for combating the virus.
“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,” says 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.”
Researchers hope to validate their mathematical models by using daily measurements of viral load and other biomarkers in patients infected with COVID-19. Also, preclinical research needs to be conducted to test the effectiveness of the immunosuppressant treatment strategy. The mathematical models indicate that this is an effective strategy, but we need hard science to back this up.
The study is published in The Journal of Medical Virology.
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