Natural killer cells and unconventional T cells in COVID-19

•NK cells and unconventional T cells are robustly activated in SARS-CoV-2 infection.•Both populations of cells also home to lung tissue during acute infection.•Severe COVID-19 associate with adaptive-like NK cell expansions and dysfunction.•An IFN-α/IL-18 imbalance drives MAIT cells and is linked to severe disease. NK cells and diverse populations of unconventional T cells, such as MAIT cells, γδ T cells, invariant NKT cells, and DNTɑβ cells are important early effector lymphocytes. While some of these cells, such as NK cell and MAIT cells, have well-established roles in antiviral defense, the function of other populations remains more elusive. Here, we summarize and discuss current knowledge on NK cell and unconventional T cell responses to SARS-CoV-2 infection. Also covered is the role of these cells in the pathogenesis of severe COVID-19. Understanding the early, both systemic and local (lung), effector lymphocyte response in this novel disease will likely aid ongoing efforts to combat the pandemic.