ABSTRACT
BACKGROUND: Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. OBJECTIVE: We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. METHODS: We performed RNA sequencing and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved PBMCs. RESULTS: In RNA-sequencing analysis, the NK cells exhibited distinctive features compared with healthy donors, with significant enrichment of proinflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg NK-cell population expanded in cryopreserved PBMCs from patients with COVID-19 regardless of disease severity, accompanied by decreased NK-cell cytotoxicity. The NK-cell population was rapidly normalized alongside the disappearance of unconventional CD56dimCD16neg NK cells and the recovery of NK-cell cytotoxicity in patients with mild COVID-19, but this occurred slowly in patients with severe COVID-19. CONCLUSIONS: The current longitudinal study provides a deep understanding of the NK-cell biology in COVID-19.
Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , Lymphocyte Activation , SARS-CoV-2/immunology , Adult , COVID-19/pathology , Humans , Killer Cells, Natural/pathology , Longitudinal Studies , Male , Middle Aged , Prospective Studies , RNA-SeqABSTRACT
BACKGROUND: NK cells seem to be mainly involved in COVID-19 pneumonia. Little is known about NKT cells which represent a bridge between innate and adaptive immunity. METHODS: We characterized peripheral blood T, NK and NKT cells in 45 patients with COVID-19 pneumonia (COVID-19 subjects) and 19 healthy donors (HDs). According to the severity of the disease, we stratified COVID-19 subjects into severe and non-severe groups. RESULTS: Compared to HDs, COVID-19 subjects showed higher percentages of NK CD57+ and CD56dim NK cells and lower percentages of NKT and CD56bright cells. In the severe group we found a significantly lower percentage of NKT cells. In a multiple logistic regression analysis, NKT cell was independently associated with the severity of the disease. CONCLUSIONS: The low percentage of NKT cells in peripheral blood of COVID-19 subjects and the independent association with the severity of the disease suggests a potential role of this subset.