PMC:7324763 / 12967-15993 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7324763","sourcedb":"PMC","sourceid":"7324763","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7324763","text":"NK Cell Dysfunction Is Linked With Increased Viral Susceptibility\nThe relevance of NK cells in fighting viral infections has been highlighted by several studies where NK cells, in mice and humans, were not present or had compromised functions (96). For example, individuals with NK cell deficiencies (NKD), a subset of primary immunodeficiency diseases, are highly susceptible to viral infection, particularly by herpesvirus and papillomavirus families (96). The seminal 1989 case of NKD in an adolescent female with severe herpesvirus infections (varicella pneumonia, disseminated CMV, and disseminated HSV) revealed how functional NK cell deficiencies have clinical consequences in terms of viral infections (97). Cancer patients are also at risk of viral infections (98), which may be explained, at least in part, by an impairment of NK cell responses often observed in humans and in murine tumor models (99–104).\nUnsurprisingly, cancer patients are at a significantly increased risk of severe COVID-19 (105, 106). Elderly patients are also more susceptible to viral infections (107). Mouse studies highlighted how a decreased number of circulating mature NK cells in aged animals paralleled with increased susceptibility to viral infections (108). Studies in humans suggest that although NK cell numbers can actually increase with aging, NK cell activity declines significantly (109, 110). Przemska-Kosicka et al. investigated NK cell function in response to seasonal influenza vaccination in young and old populations and observed quantitative and qualitative changes associated with impaired responses in the NK cell population and this was associated with poor seroconversion in the older population (111). Additionally, obesity, which has been shown to cause systemic NK cell dysfunction (112, 113), has also been linked to increased COVID-19 severity and could be the reason behind the high prevalence of severe COVID-19 in younger people (113). In short, NKD and individuals with reduced NK cell numbers or function are more susceptible to viral infections. Unsurprisingly, the CDC has already highlighted a higher risk of infection and severity of COVID-19 in older individuals and individuals with comorbidities such as obesity and cancer (114). However, this point is still controversial as a systematic review showed that primary immunodeficiencies are not linked with increased COVID-19 severity (115), but these data have to be interpreted keeping in mind that a large part of COVID-19 pathology is caused by excessive immune activation, which is arguably harder to reach in immunocompromised individuals. Given the paradoxical role of the immune response in COVID-19 patients, it would be extremely useful to be able to rely on immunological functional biomarkers that could predict the outcome of disease severity. Such assays are readily available for determining NK cell activity, e.g., NKVue™, and there is therefore an opportunity to conduct studies that would link NK cell functions to disease 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