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.