Abstract: The immune system is a general term for a whole project that can identify "non-self substances" in the organism and eliminate them. However, the immune system can sometimes cause negative results, and COVID-19 is an example of this.

The human body's immune system is the most important defense system for the human body to resist the invasion of pathogens, and it is the most effective weapon for the body to defend against the invasion of pathogens. This system consists of immune organs (bone marrow, thymus, spleen, lymph nodes, tonsils, small intestinal lymph nodes, appendix, etc.), immune cells (lymphocytes, monocytes, neutrophils, basophils, eosinophils, etc.), and immune molecules (cytokines such as complement, immunoglobulin, interferon, interleukin, tumor necrosis factor, etc.).
Then why can't the immune system help us fight against SARS-CoV-2? In fact, the immune system may even cause lethal side effects during the development of Coronavirus Disease 2019 (COVID-19).
· Excessive Defense of the Immune System
Some viruses have reached a consensus with the immune system in their long-term symbiosis with humans, and only cause local inflammation. However, the human immune system has never met SARS-CoV-2 before and it believes that this enemy is powerful, so it calls on the immune system to work at full stretch to kill it. At this time, a cytokine storm is particularly prone to occur—the immune cells react too fast and too strong, so that it is not the virus itself that kills people, but the immune response caused by the virus.
Cytokine storm is a signal for help, the purpose is to make the immune system full of fire in an instant. This last resort suicide attack can damage the virus, but it also leaves a lot of collateral damage. The blood vessels have withstood the main offensive. Cytokine storms make blood vessel walls easier to penetrate. As a result, arteries, veins, and capillaries all begin to leak blood and plasma, which eventually leads to failure of multiple organs.
· Cytokine Storm and Complement System
Complement is a group of heat-labile proteins with enzymatic activity in serum and tissue fluid. Complement is a multi-molecular system composed of more than 30 soluble proteins, membrane-bound proteins and complement receptors, so it is called the complement system. It plays an important immune and physiological function in the human body. When some factors cause its expression to be abnormal, it can cause disease damage.
Previously, in MERS, SARS, H5N1, H1N1 and other related studies, researchers found that after highly pathogenic virus infection, the complement system is overactivated to produce complement component C5a (C5a), and then cause the C5a concentration to rise rapidly in the lungs and form a positive circulating cascade reaction, which induces a cytokine storm, and eventually develops into severe pneumonia and acute respiratory distress syndrome, endangering the lives of patients.
Therefore, the pathogenic logic of COVID-19, a highly pathogenic coronavirus, is as follows:
Viral infection—overactivation of complement—cytokine storm—respiratory distress syndrome—multiple organ failure
· Complement Regulation
Scientists have done a lot of research on C5a of the complement system, and came to the following conclusions.
1. In response to the cytokine storm induced by H7N9 infection, scientists have used antibody drugs against C5a to adjust the molecular expression level of complement system, which proved that it can greatly reduce the cytokine storm and significantly reduce the pathological damage of lung tissue, thereby being able to effectively treat severe pneumonia resulting from virus infections.
2. Similar results were also found in the H5N1 study. Anti-C5a antibodies can reduce lung damage and neutrophil infiltration caused by H5N1 virus infection in mice, and reduce mortality.
3. In the related research of MERS-CoV, scientists also found that the use of antibodies against C5a receptor (C5aR1) can also reduce the level of cytokines, and the lung damage of animals receiving antibody administration was significantly reduced, indicating that by inhibiting C5a signals can inhibit the overactivation of the complement system, thereby inhibiting the cytokine storm induced by viral infection.
In response to the current COVID-19, scientists are still working on how to use the characteristics of the complement system to develop safe and effective drugs to prevent the generation of cytokine storms.