Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci-symptomatic, extremely severe clinical forms are observed. In this case, complex immune dysregulations and an excessive inflammatory response are reported and are the main cause of morbidity and mortality. Natural killer cells are key players in the control of viral infection, and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study, we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 patients suffering from neurological conditions who recovered from mild, moderate, or severe SARS-CoV-2 infection, comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection. An increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12035-021-02517-4.
Highlights
The COVID-19 is provoked by the Coronaviridae SARSCoV-2, a single strain RNA virus characterized by an extremely high infectivity but a relatively low pathogenicity
We performed an analysis of innate immune responses in a group of patients affected by neurological conditions who either were recovering from SARS-CoV-2 infection or were never infected by the virus, with a focus on Neurobiol killer (NK) cells
Results of phenotypic analyses showed that patients recovering from severe COVID-19 are characterized by a peculiar skewing in NK cell subpopulations
Summary
The COVID-19 is provoked by the Coronaviridae SARSCoV-2, a single strain RNA virus characterized by an extremely high infectivity but a relatively low pathogenicity. Mol Neurobiol killer (NK) cells, a population of immune cells that is extremely important in integrating innate and adaptive immune responses [6, 7]. The killer cell immunoglobulin (Ig)-like receptors (KIRs) and the inhibitory receptors immunoglobulin-like transcript ILT-2 are the best described of such receptors, and ligate shared allelic determinants of HLA class I molecules as well as HLA-G on target cells [11]. These interactions regulate NK activity, as NK cell activation or lack thereof is the consequence of a delicate balance between signals that are generated from activating and inhibitory receptors belonging to many families
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