Over-reaction of immune or “complicit” in cytokine storms

Recently, the Journal of Medical Virology published a study led by Weiming Yuan and Sean Quan Du, professors at the Keck School of Medicine at the University of Southern California. The study suggests that adverse interactions between the body’s two defense systems (congenital and adaptive immune responses) may trigger an over-immune response. Viruses such as the new coronary virus (SARS-CoV-2) can be deadly when the body’s immune system overreacts to infection, triggering a so-called “cytokine storm.”

Cytokines are small proteins that participate in cell signaling and help raise immune cells to the site of infection. However, an excess of cytokines can lead to excessive inflammation in some people’s areas of infection (e.g. in the lungs of patients with neo-coronary pneumonia coVID-19), severe lying to the organs and death. The researchers believe that temporarily suppressing the human immune infection system in the early stages of COVID-19 can help prevent severe symptoms and death.

Build a model to explore immune system responses

To better understand how the body’s immune system responds to patients with COVID-19, Du and Yuan used a common mathematical model called the Target Cell Limiting Model, in order to better understand how the immune system of patients in patients with influenza is better known.

The incubation period for influenza viruses is typically about 48 hours, during which time the virus targets cells on the surface of the upper respiratory tract. Because the flu virus moves so quickly that it can kill almost all “target cells” in a matter of days, the innate immune system first responds to and removes the virus and fragile cells, and then triggers an adaptive immune response a few days later to kill any remaining viruses, while activating the body’s “heavy weapons” – T-cells and B-cells.

Unlike influenza viruses, SARS-CoV-2 has a longer incubation period (about 6 days on average), invades the host slowly, and infects cells throughout the respiratory system.

The team’s model suggests that adaptive immune responses may begin to work before the innate immune system gets its job done, eventually interfering with its ability to eliminate the initial infection.

“The most dangerous thing is that as the infection continues, the body’s entire adaptive immune response reaches all levels. “Yuan believes that the longer SARS-CoV-2 is active, the more likely it is that the immune system overreacts, known as cytokine storms, which cause tissue damage.

Yuan says the flu virus can almost completely deplete the virus’s target cells within a few days, but the slow progression of COVID-19 means that adaptive immune responses can weaken before infection reaches its peak, minimizing the depletion of the virus’s target cells, leaving a large number of uninfected cells for future infections.

Early infection, use of immunosuppressants

“This situation is similar to rampant forest fires. If you just wait and see, when all the trees are burned, the fire will lose fuel and quickly extinguish. If you go all out to put out the fire before then, only part of the fire can be controlled. Once the fire was stopped, the fire returned until all the trees were burned. Du uses the above analogy to describe cytokine storms caused by SARS-CoV-2.

The researchers believe this is why many seriously ill patients are unable to leave their hospital beds and eventually develop acute respiratory distress syndrome and multiple organ failure.

In addition, this hypothesis may provide an explanation for the recurrence of the disease in patients who have “recovered” after a few weeks. Du added: “Some COVID-19 patients may relapse after significantly reduced symptoms. The combined effects of adaptive immunization and congenital immune response may temporarily reduce the virus to lower levels. But if it is not completely removed and the target cells regenerate, the virus will once again take advantage and reach another peak. “

In view of this, the researchers recommend that, in the early stages of infection, immunosuppressants should be used in the clinic to treat patients to reduce the interference of adaptive immunity.

“This is based on mathematical model studies that use the right inhibitors, or can delay the adaptive immune response and prevent it from interfering with the innate immune response, thus eliminating viruses and infected cells more quickly.” In the future, Du says, they will also verify the results of the study and test the daily viral load and other biomarkers of COVID-19 patients.

Related papers: https://doi.org/10.1002/jmv.25866