Does Your Immune Response Actually Worsen the Coronavirus?

A new study supported by the National Institute of Allergy and Infectious Diseases suggests a skewed immunological response to COVID-19 could have a significant impact on the severity of symptoms. Conducted by researchers at the Keck School of Medicine at the University of Southern California (USC), the study claims that progression of the disease can be slowed by muzzling the immune system during the early stages of infection. This prevents it from going into overdrive, which can hinder the body’s ability to kill off the virus completely and lead to the development of severe symptoms.

The importance of immunological timing

When the body contracts COVID-19 the immune system immediately responds with a first line of defence. This is known as the innate immune response and sees the body attempt to kill off the virus and prevent the spread of foreign pathogens. Several days later, the body generates a second line of immunological defence to kill off any remaining traces of the virus. This is created using information such as T cells and B cells gathered during phase one of the attack.

When the flu virus infiltrates the body, it attacks and kills most target cells in the upper respiratory system within a matter of days. The lack of targets then prevents the virus from spreading and allows the body’s innate immune response to kill off most pathogens before the adaptive response is activated. With COVID-19, researchers warn the adaptive response, i.e the second wave, could be arriving too soon. The novel coronavirus progresses much slower, with an incubation period of around six days. Using the target cell-limited model, Yuan and his team found that the adaptive immune response could be triggered too soon in COVID-19 patients, preventing the innate response from killing off most of the cells and compromising the body’s ability to eliminate the virus quickly and efficiently.

Employing target cell-limited modelling

The findings were published in the Journal of Medical Virology, with co-corresponding author of the study Weiming Yuan explaining how the team used the target cell-limited modelling to map out the progress of COVID-19.

“The danger is, as the infection keeps going on, it will mobilise the whole of the adaptive immune response with its multiple layers," says Yuan, an associate professor in the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of 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."

Explaining the resurgence

The team says this bad immunological timing could explain why some COVID-19 patients appear to improve, then suddenly deteriorate. “Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms," says lead author of the study 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.”

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