LitCovid-sentences  

PMC:7456455 / 7306-25430 JSONTXT 13 Projects

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Id Subject Object Predicate Lexical cue
T44 0-21 Sentence denotes 3 COVID-19 infection
T45 22-102 Sentence denotes 3.1 It is customary to divide the course of the infection into different stages:
T46 103-252 Sentence denotes Preinfection (co-morbidities), asymptomatic, early clinical, severe clinical (acute respiratory distress syndrome–ARDS), and recovery [8,9], Fig. 2 .
T47 253-391 Sentence denotes This natural timing should be used to establish key point-of-care sampling timepoints, avoiding patient discomfort and to focus resources.
T48 392-681 Sentence denotes Infection can progress or be aborted at every stage, presenting a dynamic continuum, to which macrophages and monocytes contribute, together with other immune and non-immune elements; MPS contributions to COVID-19 resistance and pathogenesis are still underestimated and poorly understood.
T49 682-803 Sentence denotes Fig. 2 Decision points that determine the outcome of COVID-19 infection and requirements for a monocyte activation assay.
T50 804-869 Sentence denotes A time and severity pattern has emerged for COVID-19 progression.
T51 870-969 Sentence denotes The first days, first and second week timelines are turning points for resolution or deterioration.
T52 970-1145 Sentence denotes Epidemiologic precision for these milestones and precise parameters will be valuable for strategic sampling and patient stratification, sparing resources and patient material.
T53 1146-1347 Sentence denotes With limited volumes of peripheral blood, a window on progression of the infection can be obtained by studying activation of the mononuclear phagocyte system, largely represented by monocytes in blood.
T54 1348-1477 Sentence denotes The cells are biosynthetically active and relatively long lived, ideal to trace long term effects of comorbidities and infection.
T55 1478-1606 Sentence denotes We highlight selected functional categories that should be addressed in monocytes and can be adapted to particular applications.
T56 1608-1639 Sentence denotes 3.2 Co-morbidities and the mps
T57 1640-1815 Sentence denotes Macrophage activities contribute to many co- morbidities [8,9], including aging [28], obesity [29], diabetes [30], exposure to pollutants [31], and microbiome properties [32].
T58 1816-1956 Sentence denotes Macrophage functions alter with age, together with adaptive immune processes such as thymic involution, which deplete T lymphocyte reserves.
T59 1957-2052 Sentence denotes Chronic, low grade inflammation (INFLAMMAGING) has been proposed as a predisposing factor [33].
T60 2053-2273 Sentence denotes This may result from failure of macrophages and NK cells to clear increasing accumulation of senescent cells, that enhance basal levels of inflammation and interfere with subsequent adaptive immunity upon infection [28].
T61 2274-2444 Sentence denotes Baseline inflammation may not be detrimental in itself, but can initiate an inflammatory cascade that amplifies excessive inflammation occurring in response to pathogens.
T62 2445-2637 Sentence denotes Age-related metabolic correlates of macrophage dysfunction include innate lymphoid cell interactions with adipose tissue and associated macrophages, as well as inflammasome activation [34,35].
T63 2638-2839 Sentence denotes This affects thermogenesis, part of a wider metabolic syndrome involving glucose and lipid metabolism [36], elevated body mass index (BMI), type 1 and type 2 diabetes, obesity and atherosclerosis [37].
T64 2840-2991 Sentence denotes These correlate with macrophage metabolic and mitochondrial activities [38] and, possibly, ACE2 expression and hypertension, another co-morbidity [37].
T65 2992-3240 Sentence denotes ACE2, the COVID-19 entry receptor, is widely expressed on microvascular endothelium and binds the SARS-CoV2 spike glycoprotein implicated in angiotensin regulation by its competition with ACE1, and potential role as an anti-inflammatory agent [39].
T66 3241-3469 Sentence denotes Macrophages in tuberculosis and sarcoidosis express ACE1 [40], but expression of ACE2 by monocytes and tissue macrophages has not been validated [41]; evidence for productive infection of macrophages via ACE2 is incomplete [15].
T67 3470-3855 Sentence denotes Macrophages express scavenger receptors including Axl and MERTK, tyrosine kinase receptors implicated in phosphatidyl serine recognition and phagocytosis of apoptotic cells [21]; Axl is a coreceptor for ACE2+ dependent infection of other cell types by COVID-19 and other enveloped viruses via surface or endocytic routes [42], the basis for a clinical trial involving an Axl inhibitor.
T68 3856-4025 Sentence denotes Alveolar macrophages [43] are close to Type 1 pneumocytes, involved in gas exchange, Type 2 surfactant-producing pneumocytes, and capillary endothelium, all ACE 2+ [43].
T69 4026-4298 Sentence denotes They take up and store atmospheric pollutants and poorly-degradable pro-inflammatory particles; host DNA from dying cells can induce the innate STING pathway after uptake and also activate inflammasomes in lung macrophages after exposure to ozone and cigarette smoke [31].
T70 4299-4499 Sentence denotes Other airway predisposing conditions involving macrophages [8,9], include genetic disorders such as fibrocystic disease and structural abnormalities associated with chronic inflammation and infection.
T71 4500-4680 Sentence denotes Chronic infections in which TH1-activated macrophages play a major role, tuberculosis and AIDS, enhance the risk of severe infection, with odds ratios of 1.7 and 2.3– respectively.
T72 4681-4803 Sentence denotes TH2-dependent asthma may not enhance COVID-19 susceptibility, possibly correlated with low levels of ACE2 expression [44].
T73 4804-4906 Sentence denotes IL-13 also reduces ACE2 expression, suggesting that M2-macrophages may contribute to viral resistance.
T74 4907-5028 Sentence denotes BCG and other immunisations may transiently promote non-specific resistance to SARS-CoV2 [45], to be confirmed in trials.
T75 5029-5231 Sentence denotes Mononuclear phagocytes are implicated in selected genetic [46] or acquired systemic immunodeficiency, immunosuppression and autoimmunity, including chronic renal disease requiring organ transplantation.
T76 5232-5404 Sentence denotes Tumor associated macrophages (TAM) and Myeloid derived suppressor cells (MDSC) promote malignancy and metastasis, and with chemo-and radiotherapy may enhance COVID-19 risk.
T77 5405-5535 Sentence denotes Microglia contribute to neurodegeneration through interaction with neurons in Alzheimer disease, a comorbidity independent of age.
T78 5536-5844 Sentence denotes Comorbidities are likely to be multifactorial, and not all display an obvious macrophage link; for example, the ACE2 locus on the X chromosome [47] may contribute to the decreased risk of females [48], but genetic and environmental factors underlying gender, racial and individual disparities remain unclear.
T79 5845-6104 Sentence denotes Therapeutics for many comorbidities impact on macrophage inflammatory and metabolic functions, including statins, sugar stabilizers, anti-hypertensives and anti-inflammatory agents; control of diabetes and obesity are important in preventing severe infection.
T80 6105-6316 Sentence denotes Glucocorticoids, which have potent anti-inflammatory effects on macrophages, are contra-indicated in early infection, while protecting against severe disease; timing of administration is therefore critical [49].
T81 6317-6459 Sentence denotes The use of anti-TNF antibody in treatment of rheumatoid arthritis, protects against subsequent severe COVID-19 requiring hospitalization [50].
T82 6460-6596 Sentence denotes In conclusion, the present evidence for a common macrophage contribution to a range of comorbidities is correlative, rather than causal.
T83 6597-6681 Sentence denotes Nor is it clear whether they increase the risk as well as the severity of infection.
T84 6682-6841 Sentence denotes Macrophages are central to inflammation, immunity and metabolic diseases, but further genetic and cellular studies are needed to provide a unifying hypothesis.
T85 6843-6888 Sentence denotes 3.3 Asymptomatic and initial, mild infection
T86 6889-7125 Sentence denotes There is little direct evidence how monocytes and tissue macrophages contribute to asymptomatic infection, but their tissue distribution, receptor repertoire and secretory capacity are vital to viral resistance as well as dissemination.
T87 7126-7272 Sentence denotes Acute macrophage antiviral and inflammatory responses determine the outcome of infection, together with other innate and adaptive host mechanisms.
T88 7273-7552 Sentence denotes We outline evidence from clinical [20] and experimental observations from earlier [51] and current [20] coronavirus studies and consider the role of macrophages and monocytes in local and systemic infections, the antiviral and inflammatory response, resolution and complications.
T89 7553-7728 Sentence denotes Most COVID-19 infections follow droplet inhalation and upper respiratory airway infection, which can be asymptomatic or mild, depending on mucosal immunity and IgA protection.
T90 7729-7807 Sentence denotes Nasopharyngeal epithelium expresses ACE2 and is an early target for infection.
T91 7808-8098 Sentence denotes Even if local tissue macrophages do not express ACE2 receptors and are not directly infected, they play a role in inflammatory cytokine responses to infected cells through surface, endosomal and cytosolic receptors and secretion of IL-1 family members [52] and antiviral interferons (IFNs).
T92 8099-8252 Sentence denotes Monocytes, dendritic cells and tissue macrophages can bind virus through lectin-like receptors such as CD169 [53], for transport to regional lymph nodes.
T93 8253-8385 Sentence denotes Delivery of virus droplets to the lower respiratory tract leads to infection of ACE2+ alveolar epithelium and capillary endothelium.
T94 8386-8546 Sentence denotes Detection of intracellular RNA in alveolar macrophages could result from uptake of infected epithelial and endothelial cell debris rather than active infection.
T95 8547-8741 Sentence denotes Single cell mRNA studies of bronchoalveolar lavage in COVID-19, have confirmed the recruitment of inflammatory monocytes as well as the presence of reactive alveolar macrophages in lung [17,18].
T96 8742-8959 Sentence denotes Several common symptoms of early infection can be the indirect result of epithelial cell necrosis by viral infection mediated by ACE2 and/or other co-receptors, such as transmembrane protease serine 2, (TMPRSS2) [13].
T97 8960-9167 Sentence denotes Uptake of virus or epithelial cell debris by lung macrophages can initiate inflammasome activation by P2RX7 and release IL-1β, Type1 IFN, IL-6 and TNF [3], contributing to fever, pain, lethargy and headache.
T98 9168-9290 Sentence denotes Raised levels of C-reactive protein (CRP), induced in hepatocytes by IL-6, are acute phase, plasma biomarkers of COVID-19.
T99 9291-9435 Sentence denotes Other macrophage products include chemokines such as IL-8 (CXCL8) and MCP-1 (CCL2), recruiting abundant PMN and monocytes to sites of infection.
T100 9436-9753 Sentence denotes Through viraemia COVID-19 reaches systemic organs such as heart, gut, brain and kidney, which contain resident and recruited macrophage populations; these contribute to local, specialised dysfunctions, such as myocarditis and cardiac arrhythmia, following interactions of macrophages and infected cardiomyocytes [54].
T101 9754-9908 Sentence denotes Intravascular coagulation [3,24] promotes dissemination of microthrombi-emboli to lungs, heart and brain, and fibrin degradation d-dimers appear in blood.
T102 9909-9999 Sentence denotes This is evidence of early resolution, enhanced by the generation of antiviral IgM and IgG.
T103 10000-10240 Sentence denotes We have little understanding of the innate and adaptive mechanisms that fail to clear local viral infection and at what stage IFN [55,56], other pro-inflammatory [57] and haematopoietic responses become dysregulated in blood monocytes [58].
T104 10241-10344 Sentence denotes Together with compromised lung oxygenation, this can lead to systemic immune and vascular dysfunctions.
T105 10345-10461 Sentence denotes A syndrome of mild infection in younger subjects gives rise to chilblain-like inflammation in toes and fingers [59].
T106 10462-10594 Sentence denotes The uncommon multisystem Kawasaki-like inflammatory syndrome of children results from atypical immune responses to COVID-19 [60,61].
T107 10595-10719 Sentence denotes This involves anti-viral antibody, systemic vasculitis affecting heart rather than lung, and can respond to corticosteroids.
T108 10720-11086 Sentence denotes Apart from platelet activation, mononuclear phagocytes are known to produce tissue factor and other procoagulants [62], Factors 5 and 13; fibrinolysis by vascular endothelium and inflammatory macrophages [63] is mediated by secretion of urokinase, which cleaves plasminogen to plasmin; its activity is regulated by inhibitors in plasma, such as alpha2 macroglobulin.
T109 11087-11250 Sentence denotes Anticoagulants and intranasal or inhaled Type1 IFN may be useful inhibitors of thrombosis and local viral infection, limiting progression to more severe infection.
T110 11252-11318 Sentence denotes 3.4 Moderate and severe infection: the hyperinflammatory syndrome
T111 11319-11534 Sentence denotes Between 8–12 days after COVID-19 infection, patients can progress to severe lung infection characterized by pneumonia, increased vascular permeability, edema, and hypoxia, requiring oxygen or mechanical ventilation.
T112 11535-11676 Sentence denotes This is part of a systemic viral infection of ACE2+epithelia and endothelia, widespread cell death, ischaemia, hypotension and organ failure.
T113 11677-11827 Sentence denotes Blood analysis at time of hospitalization, has revealed polymorphonuclear leukocytosis, altered levels of abnormal monocytes and lymphopaenia [58,64].
T114 11828-11963 Sentence denotes Myeloid cell recruitment to lung contributes to the hyperinflammatory and coagulopathy acute respiratory distress syndrome (ARDS) [20].
T115 11964-12053 Sentence denotes This is accompanied by monocyte/macrophage dysregulated production of secretory products.
T116 12054-12470 Sentence denotes It is not clear which factors contribute to this complication: enhanced viral growth–perhaps triggered by early, poorly neutralizing IgM and complement or IgG, hypoxia and loss of antiviral mechanisms of macrophages–directly or secondary to lymphopaenia, massive local epithelial and endothelial necrosis, hyperactivation of newly recruited immature monocytes, or a “perfect storm” encompassing several of the above.
T117 12471-12615 Sentence denotes This syndrome could be triggered by induction of ACE2 on specific populations of monocytes and macrophages, resulting in their direct infection.
T118 12616-12710 Sentence denotes By this stage, spleen and draining nodes at sites of infection are severely disorganized [65].
T119 12711-12882 Sentence denotes M1-like monocytes carrying virus through CD169 or other receptors, whether infected or not, can disseminate the virus throughout the body by a Trojan horse mechanism [66].
T120 12883-13049 Sentence denotes It is not known whether lymphocytes, not infected, die by apoptosis or necrosis, from products of activated lymphocytes or macrophages such as TNF, or by phagoptosis.
T121 13050-13257 Sentence denotes We summarize evidence that blood monocytes and activated tissue macrophages contribute to severe COVID-19 and consider virus-induced macrophage pathogenetic mechanisms, which can be targeted therapeutically.
T122 13258-13363 Sentence denotes Earlier studies on SARS1/MERS revealed many of the features of ARDS and of macrophage involvement [6,51].
T123 13364-13531 Sentence denotes Initial blood and tissue analysis of COVID-19 provided morphologic evidence of monocyte abnormality and intense macrophage phagocytic activity in infected organs [65].
T124 13532-13770 Sentence denotes FACS and single cell RNA analysis of monocytes and broncho-alveolar macrophages [18] provided evidence of emergency myelopoiesis [64] and confirmed the presence of recruited and activated macrophages in alveoli [17] and lung interstitium.
T125 13771-13959 Sentence denotes Plasma membrane opsonic and other receptors contribute to dysregulated inflammation, monocytic hyperactivation and impaired phagocytic clearance of apoptotic and necrotic cells and debris.
T126 13960-14088 Sentence denotes Acting through NFkB, RNA, DNA and other sensing and signaling pathways, they initiate production of numerous secretory products.
T127 14089-14260 Sentence denotes Particular antiviral and proinflammatory products have been targeted for anti-inflammatory treatment, including the IFNs [55,56], IL-1 family [52], IL-6 [27] and TNF [22].
T128 14261-14459 Sentence denotes In addition, mononuclear phagocytes interact with plasma cascades, and through upregulated adhesion molecules, with other myeloid and lymphoid cells, platelets, system-wide endothelia and epithelia.
T129 14460-14734 Sentence denotes Dysregulated activation of macrophages contributes to the hyperinflammatory and thrombotic pathways of severe COVID-19 [3,24,67].Virus-induced cell injury, apoptosis, necrosis and necroptosis are sensed by distinct, opposing macrophage receptor-dependent effector responses.
T130 14735-14902 Sentence denotes These include activating and inhibitory pathways of IL-1 production, processing and secretion [52,57], triggered by tissue injury, inflammasome and caspase activation.
T131 14903-15135 Sentence denotes A highly impaired type1 IFN response, characterized by no IFNβ and low IFNα production and activity, has been associated with persistent viraemia and an exacerbated inflammatory response, partially driven by NFkB, TNF and IL-6 [56].
T132 15136-15237 Sentence denotes Endogenous oxidized phospholipids reprogramme macrophage metabolism and boost hyperinflammation [68].
T133 15238-15365 Sentence denotes By capturing inflammatory lipids released from dying cells, CD14 induces inflammasome-dependent phagocyte hyperactivation [69].
T134 15366-15535 Sentence denotes Macrophage fuel production and utilization [36] are sensitive to hypoxia, HIF-1 responses [70] and iron availability, influencing M1 polarization and effector functions.
T135 15536-15735 Sentence denotes Activated macrophages trigger coagulation and complement cascades, as well as angiotensin and bradykinin pathways that dysregulate vascular tone and permeability, exacerbating inflammation and edema.
T136 15736-15929 Sentence denotes Immunological processes that may contribute to the outcome of macrophage- viral induced pathology include antibody enhancement of infection (ADE) and inflammation (ADI), and neutrophil NETosis.
T137 15930-16056 Sentence denotes Anti-spike antiserum can induce hyperinflammation via macrophage FcR, depending on IgG glycosylation and Syk involvement [71].
T138 16057-16170 Sentence denotes Cross-reacting antibodies from previous benign coronavirus infections also contribute to enhanced pathology [72].
T139 16171-16445 Sentence denotes Dendritic cell dysfunction, ascribed to down regulated HLA-DR expression [67,72] and defective antigen presentation to T and B lymphocytes, may result from lack of costimulatory signals, aborting lymphocyte proliferation and activation and mediating widespread clonal death.
T140 16446-16563 Sentence denotes Haemophagocytosis, a feature of the macrophage activation syndrome (MAS), is also observed in other viral infections.
T141 16565-16578 Sentence denotes 3.5 Recovery
T142 16579-16840 Sentence denotes Macrophages are central to the cellular processes which contribute to recovery from COVID-19 infection; they remove debris and necrotic tissue through phagocytosis and secretion of elastase and collagenase, and produce IGF1 and TGF-β to promote tissue recovery.
T143 16841-17076 Sentence denotes M2-like macrophages are the source of potent lipid metabolites which resolve inflammation; these include resolvins, protectins and maresins, short lived autacoids which regulate the magnitude and duration of acute inflammation [25,73].
T144 17077-17232 Sentence denotes Acting through macrophage GPCRs for these metabolites, they enhance efferocytosis of dying neutrophils, and counter inflammation without immunosuppression.
T145 17233-17346 Sentence denotes Recovery can be prolonged after severe infection, involving fever, lethargy, scarring and loss of organ function.
T146 17347-17488 Sentence denotes Italiani and colleagues profiled the course of resolving versus persistent inflammation with special reference to IL-1 family molecules [57].
T147 17489-17692 Sentence denotes An independent single cell mRNA analysis of peripheral blood mononuclear cells during early recovery of COVID-19 infection [23], revealed an increased ratio and level of classical CD14++IL-1β+ monocytes.
T148 17693-17928 Sentence denotes Further studies are needed to compare monocytes and tissue macrophages after mild or severe infection and to establish whether repolarisation of macrophages from M1 to an M2 phenotype can promote resolution and recovery after COVID-19.
T149 17929-18040 Sentence denotes After helminth infection, M2 macrophages express resistin, which protects against LPS-induced toxic shock [74].
T150 18041-18124 Sentence denotes New or repurposed therapies may be able to modify the sequelae of severe infection.