Suppressing immune system could provide counterintuitive COVID-19 therapy

Immunologists warn that interfering with the body's natural immune response may be dangerous.

A patient suffering from the coronavirus disease (COVID-19) is treated an the Intensive Care Unit (ICU). May 6, 2020 (photo credit: STEPHANE MAHE / REUTERS)
A patient suffering from the coronavirus disease (COVID-19) is treated an the Intensive Care Unit (ICU). May 6, 2020
(photo credit: STEPHANE MAHE / REUTERS)
Could suppressing the body's natural immune system help COVID-19 patients with severe symptoms recover from the illness? Scientists in America have suggested that it might, and are carrying out trials to test the method.
Our immune system is essential in protecting us from the germs and bacteria we encounter every day, but doctors have observed that some of the fatalities caused by COVID-19 are brought about by the immune system going into overdrive and attacking healthy cells, a process known as a cytokine storm.
Cytokine storms have been recorded as a complication of respiratory diseases such as SARS and MERS, and are thought to have been linked to the high fatality rate of the H5N1 influenza virus, also known as “bird flu.” It has also been observed in standard influenza cases. However, after running models comparing COVID-19 to the flu, researchers at the University of Southern California found that the progression of the new coronavirus was slower,
In a paper published by the Journal of Medical Virology, the researchers suggested that the slower rate may be potentially increasing the pathogenic immune response in COVID-19 patients, the South China Morning Post (SCMP) has reported.
The human immune system has two methods of fighting invasive pathogens: innate and adaptive. The innate, non-specific response is the first to kick in, quickly moving to attack foreign cells in the body as soon as they are detected. The adaptive response, which is specific to the pathogen, starts days later if the pathogen is still detected within the body.
According to the research paper, the flu has an incubation period of only 48 hours or less, during which time the virus attacks cells on the surface of the upper respiratory system, killing almost all of them within that time period. But after that, the virus has nothing to attack, leaving the way clear for the innate immune response to attack the virus in turn, clearing it from the body before the adaptive response kicks in.
With COVID-19, the virus takes longer to take hold - about six days. The researchers suggest that this gives the adaptive immune response time to activate, which can interfere with the innate response.
“The danger is, as the infection keeps going on, it will mobilize the whole of the adaptive immune response with its multiple layers,” said Weiming Yuan, an associate professor from the University of Southern California and co-author of the paper, according to SCMP.
“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.”
It may also explain why some people experience a second, more severe wave of the virus after an initial recovery period.
“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,” he said.
The researchers have suggested that suppressing the immune system within this response window could delay the adaptive immune response, giving the innate system time to clear the virus from the patient's system before the immune system goes into overload.
“Based on the results of the mathematical modelling, 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 Sean Du, a researcher from the University of Southern California and co-author of the paper, according to SCMP.
“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.”
However, not all medical professionals are in agreement with the researchers' suggestion. Ashley St. John, an immunologist at Duke University and National University of Singapore Medical School said that the proposed treatment was potentially very risky, and that a more targeted approach would be better.
“Suppressing the adaptive immune system is a very drastic step. It can be very dangerous because you’re crippling your body’s ability to clear that last bit of infection,” she said. “It’d be nice if we can find something more specific, that is causing the pathology, which tipped the balance into severe disease rather than targeting the whole adaptive immune system.”
Du pointed out that at this stage the idea was only a theory which would need experimental research to back it up, he suggested animal trials would be a good way to do that. But, he added, any drug used to suppress the system would only be active for a short time, allowing the immune system to come back in afterwards and finish the job.