(A) The use of IFNs can prevent the spread of infection by activating NK cells and preventing adjacent cells from being infected. They do this by increasing the expression of antiviral genes, and this inhibits the accumulation of neutrophils. (B) The use of an IL-6 inhibitor called tocilizumab can prevent NK cell exhaustion. In addition, the inhibition of NKG2A may be effective in preventing pathological effects of NK cells. (C) Multiple sclerosis medications including vitamin D3, MMF and natalizumab, may be used to counteract the exhaustion of NK cells by SARS-CoV-2. (D) Adaptive NK cells, a group of NK cells that express higher levels of NKG2C/CD57 and secrete more IFNs, can be produced in the laboratory using CMV-infected fibroblasts. These can be considered a treatment option for COVID-19 patients. (E) CYNK-001 is a group of NK cells derived from umbilical cord stem cells. They can detect virus infected cells and eradicate infection using stimulatory receptors such as NKG2D, DNAM and NCRs. (F) Genetically engineered cells called CAR-NK cells can also be used to treat COVID-19.
DMF: Dimethyl fumarate; MMF: Monomethyl fumarate; NK: Natural killer cell; CAR: Chimeric antigen receptors; IFN: interferons; CMV: Cytomegalovirus; MS: Multiple sclerosis; mAb: Monoclonal antibody; DNAM-1: DNAX accessory molecule-1; NCRs: Natural cytotoxicity receptors.