NK cells at the crossroads in COVID-19: a question of timing

Abstract

The outbreak of the novel coronavirus SARS-CoV-2 and the attendant physiological symptoms associated with the COVID-19 disease have led to an explosion of interest studying different aspects of the immune response. As of yet, the particular roles of natural killer cells are not well understood in this disease. NK cells are critical first-response cytotoxic cells of the innate immune system. NK cells are traditionally considered important for their roles in innate immunity against tumors and viral infected cells, as well as their ability to produce cytokines, particularly interferon-?, and participate in antibody dependent cell cytotoxicity (ADCC). Here, we describe the role of NK cells in peripheral blood and in the lungs with respect to the pathology caused by SARS-CoV-2 and discuss the implications of proposed different types of therapies on NK cells. Evidence is accumulating that NK cells play an important role in initial surveillance as part of innate immunity. With the progression of the disease and rising inflammation, these cells, when in circulation, appear to become exhausted and ineffective. In the COVID lung, however, a complex interplay between inflammatory cells, chemokines, cytokines and aberrantly activated migratory NK cells occurs, potentiating local inflammation and the critical situation in the lungs.