4.2 Other Inhibitors for cytokine storm
After the body is infected with the virus (e.g., respiratory syncytial virus), natural immunity (e.g., NK cells, macrophages) occurs within 1-3 days after infection, and then the activated immune cells will release many cytokines (e.g., interleukins, interferon) within 4-7 days, which can activate more immune cells through cascade amplification, even include T cells and B cells. In the final stage (Days 7-9), B cells may become mature and will produce some specific antibodies, or neutralizing antibodies, which can control the virus as soon as possible. In addition, the immune response of specific T cells can also control the virus (Openshaw & Tregoning, 2005). Antibodies and cytokines produced through immune activation can attack viruses. At the same time, these cytokines and activated immune cells will reach various organs with blood circulation. Once this attack is too aggressive, it is easy to attack its own substances as foreign substances, which then cause damage to organs. Therefore, when dealing with viruses, we should also pay attention to the treatment of excessive immune response. Otherwise the damage to the body still exists. Currently, new methods for treating cytokine storms can be achieved through the following main inhibitors: IL-1 inhibitors, IL-6 inhibitors (mentioned above), GM-CSF inhibitors, and JAK inhibitors.
A retrospective study on IL-1 antagonists (Anakinra) indicated that among moderate-to-severe ARDS, and hyperinflammation patients (aged ≥18 years) with COVID-19, 29 of them used high doses of IL-1 antagonists. 16 people were enrolled in the reference group. It can be seen that after 21 days of treatment, the group using the IL-1 receptor antagonist had a 10% mortality rate, and the reference group was 44%, indicating that IL-1 antagonist can reduce the mortality rate (Cavalli et al., 2020). In addition to anakinra, other anti-IL-1 antibodies, such as canakinumab, are also undergoing clinical trials.
The study found that there were two cytokines increased in novel coronavirus patients, one is IL-6, and the other is GM-CSF. An open-label clinical trial on the anti-GM-CSF receptor antibody, Mavrilimumab, revealed that among the severe patients without invasive ventilator, the experimental group was 13 people, and the control group was 26 people, then after 14 days treatment, 85% of the treatment group had improved clinical symptoms, and the control group was lower, only 42% improved. The key data was that there was zero death in the treatment group and 27% in the control group. In addition, the mortality rate of patients using mechanical ventilation is 8% in the treatment group and 35% in the control group, so the treatment also reduces this rate(Y. Zhou et al., 2020).