LitCovid-sentences  

PMC:7324763 / 27155-36277 JSONTXT 14 Projects

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Id Subject Object Predicate Lexical cue
T160 0-43 Sentence denotes NK Cell Role in Coronavirus Immunopathology
T161 44-211 Sentence denotes In the context of CoVs, the significant morbidity and mortality associated with severe disease is due to acute lung injury (ALI) and the development of ARDS (19, 141).
T162 212-476 Sentence denotes Pathological analysis of tissues obtained from SARS and MERS patients showed edematous lungs with areas of consolidation, bronchial epithelial denudation, loss of cilia, squamous metaplasia, pneumocyte hyperplasia, and bronchial submucosal gland necrosis (19, 29).
T163 477-581 Sentence denotes Histological features include diffuse alveolar damage and acute fibrinous and organizing pneumonia (29).
T164 582-713 Sentence denotes A heightened inflammatory response in the lungs resulting in tissue damage has been hypothesized to explain the development of ALI.
T165 714-823 Sentence denotes There are several key factors that may be responsible for the induction of this dangerous inflammation (138).
T166 824-1030 Sentence denotes Both SARS-CoV-1 and MERS-CoV replicate to high titers early in infection, which could lead to enhanced cytopathic effects and increased production of pro-inflammatory cytokines/chemokines by infected cells.
T167 1031-1276 Sentence denotes Chen et al. developed a pneumonia model where pulmonary replication of SARS-CoV-1 was associated with histopathological evidence of disease, including bronchiolitis, interstitial pneumonitis, diffuse alveolar damage, and fibrotic scarring (120).
T168 1277-1740 Sentence denotes They identified a biphasic cellular immune response in which cytokines (TNF-α and IL-6) and chemokines [interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, RANTES] were produced early, likely by infected airway epithelial cells, alveolar macrophages, and recruited inflammatory monocyte-macrophages and neutrophils, which have been shown to replace resident alveolar macrophages (19, 142).
T169 1741-1979 Sentence denotes SARS-CoV-1 and MERS-CoV encode structural and non-structural proteins that antagonize the interferon response, which may initially delay the innate immune response but eventually potentiate inflammatory monocyte-macrophage responses (19).
T170 1980-2130 Sentence denotes In COVID-19 patients, Liao et al. reported increased lung infiltration by macrophages identified via RNA-seq analysis of bronchoalveolar lavage fluid.
T171 2131-2372 Sentence denotes Patients with mild cases exhibited infiltration by alveolar macrophages [Fatty Acid Binding Protein (FABP)4+] while patients with severe ARDS exhibited infiltration by highly inflammatory [Ficolin (FCN1)+] monocyte-derived macrophages (128).
T172 2373-2573 Sentence denotes In the SARS-CoV-1 pneumonia model, the first wave of cytokines and chemokines induced an accumulation of NK cells, as well as plasmacytoid (p)DCs, macrophages, CD4+ T cells and NKT cells in the lungs.
T173 2574-2860 Sentence denotes A second wave of inflammatory mediators was detected later on day 7 post-infection [cytokines TNF-α, IL-6, IFN-γ, IL-2, IL-5, and chemokines MCP-1, MIP-1a, RANTES, monokine induced by gamma interferon (MIG), IP-10] and correlated with lung infiltration of T cells and neutrophils (120).
T174 2861-3152 Sentence denotes These findings are consistent with studies that have shown increased levels of activating and inhibitory cytokines and chemokines in the blood and lungs of SARS patients, as well as histological studies of SARS and MERS-infected lungs which show extensive cell infiltrates (19, 29, 143–145).
T175 3153-3335 Sentence denotes When Huang et al. investigated the cytokine/chemokine profile in the acute phase of SARS infection in a cohort of Taiwanese patients, they observed an IFN-γ-led cytokine storm (138).
T176 3336-3575 Sentence denotes They assessed sera from hospitalized patients prior to the administration of immunomodulators and found significantly increased levels of IFN-γ, IL-18, IP-10, MCP-1, MIG, and IL-8 (138), which returned to basal levels in convalescent sera.
T177 3576-3674 Sentence denotes IP-10, MIG, MCP-1, and IL-18 levels were all significantly increased in death vs. survival groups.
T178 3675-3917 Sentence denotes Interestingly, they found an inverse relationship between IFN-γ levels and lymphocyte numbers and suggested this could either be due to IFN-γ-induced lymphocyte apoptosis or sequestration of chemokine-recruited lymphocytes in the lungs (138).
T179 3918-4012 Sentence denotes Indeed, this hyper-cytokinemia has been consistently observed in SARS-infected patients (146).
T180 4013-4276 Sentence denotes However, a recent study found that levels of six pro-inflammatory cytokines (IL-1b, IL-1Ra, IL-6, IL-8, IL-18, and TNF-α) implicated in the cytokine storm in COVID-19 patients did not differ significantly from levels in cytokine storms caused by other conditions.
T181 4277-4569 Sentence denotes They suggest that it is therefore possible that increased levels of pro-inflammatory cytokines in the context of severe COVID-19 may simply reflect an increased viral burden rather than an exuberant immune response and suggest that immunotherapies should therefore be used with caution (147).
T182 4570-4896 Sentence denotes Altogether these studies show that during acute CoV infection, inflammatory monocyte-macrophages and neutrophils accumulate in the lungs and produce cytokines and chemokines that induce the activation and migration of lymphocytes, including NK cells, to the lungs, where they could be one of the main producers of IFN-γ (148).
T183 4897-5032 Sentence denotes Under normal conditions, human lung NK cells are typically hyporesponsive but dynamically migrate in and out of pulmonary tissues (83).
T184 5033-5207 Sentence denotes This supports the hypothesis that during infectious respiratory diseases, an increased recruitment of hyperresponsive NK cells would worsen the festering immunopathology (8).
T185 5208-5452 Sentence denotes In fact, through Viral-Track scanning of unmapped single-cell RNA-sequencing data, Bost et al. showed that patients with severe COVID-19 exhibited a hyperinflammatory response with an enriched and highly proliferative NK cell compartment (142).
T186 5453-5731 Sentence denotes High levels of IFN-γ leads to epithelial and endothelial cell apoptosis and vascular leakage, suboptimal T cell response, accumulation of alternatively activated macrophages and altered tissue homeostasis, and ARDS (19), all of which may contribute to COVID-19 disease severity.
T187 5732-5997 Sentence denotes In summary, the evidence is consistent with the hypothesis that NK cells are involved in the cytokine storm associated with CoV infection and that this hyper-cytokinemia contributes significantly to disease severity via inflammation-mediated lung damage (Figure 1).
T188 5998-6323 Sentence denotes Figure 1 Hypothesized dual role of NK cells during coronavirus pathogenesis. (A) Healthy Natural Killer (NK) cells in low-risk individuals recognize SARS-CoV-2 infected cells via recognition of viral proteins on the surface of infected cells and through sensing of cytokines and chemokines produced in response to infection.
T189 6324-6651 Sentence denotes These cells are hypothesized to be able to directly induce apoptosis through death receptor ligation, antibody-dependent cell-mediated cytotoxicity (ADCC), and through the release of cytotoxic granules, in addition to indirectly targeting virally infected cells via modulation of the immune response through cytokine secretion.
T190 6652-6944 Sentence denotes An effective innate immune response may be able to clear SARS-CoV-2 infection and leave the patient's lungs undamaged. (B) High risk individuals may have dysfunctional NK cells which may not recognize and respond to SARS-CoV-2 infection due to immune evasion strategies employed by the virus.
T191 6945-7180 Sentence denotes It is hypothesized that an accumulation of infected epithelial cells and innate immune cells, monocyte-macrophages and neutrophils, release cytokines, and chemokines which further recruit immune cells, including NK cells, to the lungs.
T192 7181-7248 Sentence denotes This may result in the induction of a cytokine storm, led by IFN-γ.
T193 7249-7476 Sentence denotes This inflammatory state could act as the catalyst for the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), contributing to the significant morbidity, and mortality associated with COVID-19.
T194 7477-7635 Sentence denotes SARS-CoV-2 infection is associated with reduced NK cell levels and an exhausted phenotype which may impede viral clearance, in addition to severe lung damage.
T195 7636-7741 Sentence denotes Interestingly, this duality of NK cell roles mirrors what is seen in critically ill patients with sepsis.
T196 7742-8107 Sentence denotes Studies suggest that while early NK cell stimulation and IFN-γ production is beneficial to combat infections, excessive and prolonged stimulation of NK cells leads to reduced NK cell numbers and an exhausted phenotype and was associated with increased systemic inflammation in systemic inflammatory response syndrome (SIRS)/sepsis and increased mortality (149–152).
T197 8108-8230 Sentence denotes This review of the literature suggests that NK cells may play an important role in both CoV clearance and immunopathology.
T198 8231-8391 Sentence denotes The continued probing of NK cell involvement is essential for a more complete understanding of CoV pathophysiology and for the deployment of immunotherapeutics.
T199 8392-8736 Sentence denotes Depending on the patient, the stage of disease, and other still poorly understood factors, it may be necessary to either boost NK cell activity to ensure viral clearance, e.g., at exposure or during early infection, or to finely tune NK cell effector functions in late stage infections to prevent hyper-cytokinemia and inflammatory lung damage.
T200 8737-8890 Sentence denotes Indeed, all CoVs that infect humans are zoonoses and there is an extensive reservoir of CoVs that could serve as a source for future pandemics (14, 153).
T201 8891-9122 Sentence denotes Therefore, a broader understanding of the immune response to coronaviruses and insights into therapeutic implications will be of significant value not only for the current COVID-19 pandemic, but also for potential future pandemics.