Strategies to reduce inflammation
Altered function of Th1 cells, CD4-CTL, Treg cells, NKT cells, γδT cells and MAIT cells may contribute to systemic inflammation and tissue damage in severe COVID-19 patients (as mentioned above). Th1 cells secrete IFN-γ, TNF-α, IL-6 and granulocyte–macrophage colony-stimulating factor (GM-CSF). Subsequently, GM-CSF may also trigger monocytes for further production of IL-6 [97]. Avoiding severe inflammation should be considered as an effective strategy for alleviating symptom of COVID-19 infection. Steroids (dexamethasone) and anti-cytokines, notably interleukin-6 (IL-6) antagonists (Tocilizumab, Sarilumab, and Siltuximab), GM-CSF inhibitors (Mavrilimumab and Gimsilumab), IFN-γ inhibitors (Emapalumab) may be current candidates [98, 99]. Besides, low level of IL-2 in later stage of infection could be beneficial in expanding Tregs in COVID-19 patients to control excessive inflammation [100, 101]. MAIT cells expressed high level of IL-18 receptor and can be activated by IL-18 [102], indicating IL-18 blockade might represent a therapeutic option for COVID-19 patients. Early control of the inflammation through therapies is essential to decrease mortality rate of patients with COVID‐19.
So far, there is no proven specific anti-SARS-CoV-2 therapy in clinic. More therapeutic strategies or combination therapy under clinical trials to enhance T cell function, revert T-cell exhaustion and alleviate inflammation need to be evaluated according to the clinical outcomes.