Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review.

Exaggerated immune response and cytokine storm are accounted for the severity of COVID-19, including organ dysfunction, especially progressive respiratory failure and generalized coagulopathy. Uncontrolled activation of complement contributes to acute and chronic inflammation, the generation of cytokine storm, intravascular coagulation and cell/tissue damage, which may be a favorable target for the treatment of multiple organ failure and reduction of mortality in critically ill patients with COVID-19. Cytokine storm suppression therapy can alleviate the symptoms of critically ill patients to some extent, but as a remedial etiological measure, its long-term efficacy is still questionable. Anti-complement therapy has undoubtedly become an important hotspot in the upstream regulation of cytokine storm. However, chemosynthetic complement inhibitors are expensive, and their drug resistance and long-term side effects require further investigation. New complement inhibitors with high efficiency and low toxicity can be obtained from natural products at low development cost. This paper puts forward some insights of the development of natural anti-complement products in traditional Chinese medicine, that may provide a bright perspective for suppressing cytokine storm in critically ill patients with COVID-19.