Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients

Abstract

Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two consecutively negative SARS-CoV-2 viral RNA test ( interval ≥ 24 hours), improved respiratory symptoms and obvious absorption of inflammation in pulmonary imaging are the discharge criteria for COVID-19 patients. The clearance profile of viral RNA in the upper respiratory tract specimens, including nasopharyngeal swab and/or oropharyngeal swabs, is related to innate immune cells such as Natural Killer cells. A total of 168 patients were included for the study. In this cohort, non-severe and severe groups showed significant differences in white blood cells, neutrophils, lymphocytes, basophils and platelets counts, as well as in infection related parameters such as CRP and serum cytokine IL-6. For lymphocyte subsets tests at admission, the severe group displayed significantly lower cell counts than the non-severe group. Higher counts of total T cells, CD4 + T cells, CD8 + T cells, and NK cells in peripheral blood showed a significant correlation with the shorter time taken to obtain the first negative viral RNA test and first positive IgM/ IgG antibody test. The number of B cells was only correlated with time to achieve the first positive IgM/IgG test. The count of NK cells was also correlated with a higher level of IgG antibody (p = 0.025). The lymphocytopenia group had a significantly worse survival rate (p = 0.022) and a longer duration (p = 0.023) of viral shedding than the normal lymphocyte count group. A lower NK cell count correlates the most with the worse survival rate (p<0.001) and a longer duration (p<0.001) of viral shedding. This study suggests the potential value of allo-Natural Killer cell therapy as an universal COVID-19 treatment strategy.

An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia

“…We find that GTEx lung eQTLs lie closer to predicted causal mutations among the 42 putative selected loci than for any other tissue (p = 3.10 À5 ; Figure 7). Several additional tissues known to be negatively affected by coronavirus-blood and arteries, 43,44 adipose tissue, 45 and the digestive tract 46 -also exhibit closer proximities between putative causal loci and eQTLs than expected by chance (Figure 7). Interestingly, the spleen shows no tendency for eQTLs to lie closer to selected loci than expected around 900 generations ago compared to other evolutionary times, perhaps because the spleen is replete with multiple immune cell types that might be more prone to regular adaptation to diverse pathogens over time.…”

SARS-CoV-2 Variants, Vaccines, and Host Immunity

“…Type I IFN responses induce the maturation of DCs, monocytes and macrophages into antigen presenting cells (APCs) that display viral antigenic peptides complexed with major histocompatibility complex (MHC) class II (27)(28)(29)(30). NK cells conduct active cross-talk with DCs and play a role in antigenpresentation (16). APCs facilitate the activation of naïve cluster of differentiation (CD)4 + and CD8 + T-lymphocytes as well as regulatory T-lymphocytes (Treg) through T-cell receptor (TCR) binding (27)(28)(29)(30) (Figure 1).…”

“…Viral detection triggers the activation of various transcription factors resulting in the secretion of pro-inflammatory chemokines and cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 and IL-6, amongst others, by monocytes, macrophages, neutrophils, and dendritic cells (DCs) that home to the site of infection ( 12 , 13 , 15 ). The release of these cytokines also stimulates natural killer (NK) cells that are responsible for directly killing virus-infected cells through degranulation and receptor mediated apoptosis ( 16 ). Antiviral responses are amplified by inducing the expression of type I interferons (IFN) and subsequent interferon-stimulated genes (ISGs) ( 12 , 13 , 15 ).…”

Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

“…For disease treatment using NK cells, NK-cell-based adoptive immunotherapy has been introduced for cancer treatment and has been considered for viral infections [19,127,128]. To obtain convincing evidence of the importance of NK cells for disease treatment, it is necessary to treat cancer or viral infections using the combination of NK cell therapy and lifestyle improvement.…”