LitCovid-sentences  

PMC:7200337 / 87516-93973 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T499 0-37 Sentence denotes Cytokine-Directed Therapy in COVID-19
T500 39-80 Sentence denotes Recombinant IFN as an Antiviral Treatment
T501 81-200 Sentence denotes One of the first defenses of the human body against RNA viruses like SARS-CoV-2 is the release of types I and III IFNs.
T502 201-431 Sentence denotes It is important to note that type I IFN (IFNα/β) receptors are ubiquitously expressed, so IFNα/β signaling can result in not only antiviral effects, but also the activation of immune cells that potentially exacerbate pathogenesis.
T503 432-563 Sentence denotes In contrast, type III IFN (also known as IFNλ) signals mainly in epithelial cells, as well as in a restricted pool of immune cells.
T504 564-777 Sentence denotes Because type III IFNs have immunomodulatory functions, subsequent signaling could induce a potent antiviral effect without enhancing pathogenic inflammation (Andreakos et al., 2017, Prokunina-Olsson et al., 2020).
T505 778-922 Sentence denotes Recently, there has been a growing interest in the potential therapeutic impact of modulating the IFN response to disable COVID-19 pathogenesis.
T506 923-1025 Sentence denotes Before the current pandemic, groups have studied the role of IFNs in other betacoronavirus infections.
T507 1026-1179 Sentence denotes One study of 40 patients with SARS-CoV-1 infection described unresolved elevated type I IFNs and ISGs in those with poor outcomes (Cameron et al., 2007).
T508 1180-1459 Sentence denotes Others report that exogenous type I IFN does not improve outcomes when given with ribavirin in patients with MERS-CoV infection (Arabi et al., 2020), suggesting that the role of IFN as a therapeutic or prophylactic option may be strain or species specific (Sheahan et al., 2020).
T509 1460-1710 Sentence denotes Interestingly, a recent study by Mount Sinai virology groups revealed that type I IFN signaling is impaired in the early response to SARS-CoV-2; in vitro, SARS-CoV-2 may be more susceptible to type I IFN than SARS-CoV-1 is (Blanco-Melo et al., 2020).
T510 1711-1997 Sentence denotes Based on additional evidence that IFN responses to betacoronaviruses are altered as compared to other respiratory viruses (Blanco-Melo et al., 2020, Channappanavar et al., 2016, Okabayashi et al., 2006), trials of IFN-I/III administration have been initiated (NCT04343976, NCT04331899).
T511 1999-2016 Sentence denotes Cytokine Blockade
T512 2017-2291 Sentence denotes Hyperinflammatory responses and elevated levels of inflammatory cytokines, including IL-6, -8, and -10, have been shown to correlate with COVID-19 severity (Chen et al., 2020h, Diao et al., 2020, Gong et al., 2020, Moore and June, 2020, Wan et al., 2020a, Xu et al., 2020b).
T513 2292-2449 Sentence denotes The drivers of this cytokine storm remain to be established, but they are likely triggered initially by a combination of viral PAMPs and host danger signals.
T514 2450-2608 Sentence denotes The heterogeneous response between patients suggests other factors are involved, possibly including the SARS-CoV-2 receptor, ACE2 (Hirano and Murakami, 2020).
T515 2609-2740 Sentence denotes Several studies have begun to report the cellular programs that may contribute to the cytokine storm detected in COVID-19 patients.
T516 2741-2995 Sentence denotes One group reported that in the context of generalized lymphopenia, certain subsets of CD4 T cells that express GM-CSF and IL-6 are more abundant in severe COVID-19 patients than in COVID-19 patients who do not require intensive care (Zhou et al., 2020b).
T517 2996-3234 Sentence denotes Reports that other major proinflammatory cytokines (TNF-α, IFN-ɣ, IL-2) and chemokines (CCL2, CCL3, CCL4) are elevated underscore a potentially pathogenic TH1/2 program in COVID-19 (Diao et al., 2020, Giamarellos-Bourboulis et al., 2020).
T518 3235-3505 Sentence denotes Histological and single-cell analyses identified monocytes and macrophages as other potent sources of inflammatory cytokines in COVID-19 cytokine storm (Chen et al., 2020h, Giamarellos-Bourboulis et al., 2020, Law et al., 2005, Moore and June, 2020, Zhou et al., 2020b).
T519 3506-3884 Sentence denotes Studies of other betacoronavirus infections, including SARS-CoV-1 and MERS-CoV, have also identified similar hyperactivation of monocytes, macrophages, and DCs as a driver of cytokine-mediated immunopathology in humans (Cheung et al., 2005, Chien et al., 2006, Huang et al., 2020c, Konig et al., 2020, Wang et al., 2005, Wong et al., 2004, Xu et al., 2020b, Zhou et al., 2020b).
T520 3885-4115 Sentence denotes Following preliminary reports of IL-6 as a critical cytokine in COVID-19-associated CRS, monoclonal antibodies that target the IL-6 signaling pathway have been proposed as therapeutic candidates (Moore and June, 2020) (Figure 6C).
T521 4116-4361 Sentence denotes The commercial anti-IL-6R antibodies tocilizumab (Actemra) and sarilumab (Kevzara) and the anti-IL-6 antibody siltuximab (Sylvant) are now being tested for efficacy in managing COVID-19 CRS and pneumonia in 13 ongoing clinical trials (Table 2 ).
T522 4362-4624 Sentence denotes To date, only one group has reported preliminary results from a cohort of 20 COVID-19 patients treated with a single administration of tocilizumab (400 mg, i.v.), along with lopinavir, methylprednisolone, and oxygen therapy (ChiCTR2000029765) (Xu et al., 2020b).
T523 4625-4812 Sentence denotes The single observation study found recuperated lymphocyte counts in 10 of 19 patients and resolution of lung opacities in 19 of 20 patients on chest CT; 19 of 20 patients were discharged.
T524 4813-4919 Sentence denotes All patients experienced an improvement in symptoms, and no subsequent pulmonary infections were reported.
T525 4920-5055 Sentence denotes A second report described an association between use of tocilizumab and reduced likelihood of ICU admission and mechanical ventilation.
T526 5056-5241 Sentence denotes Still, in 30 declining patients with severe COVID-19 pneumonia, this retrospective study did not report significant improvement in mortality on weighted analysis (Roumier et al., 2020).
T527 5242-5347 Sentence denotes Nevertheless, these studies are encouraging, but like other treatment approaches, larger RCTs are needed.
T528 5348-5426 Sentence denotes Table 2 Clinical Trials Evaluating the Efficacy of IL-6/IL-6R Blockade Therapy
T529 5427-5454 Sentence denotes Clinical Trial Intervention
T530 5455-5603 Sentence denotes NCT04331795 (COVIDOSE)NCT04320615 (COVACTA)NCT04332913 (TOSCA)NCT04317092 (TOCOVID-19)NCT04335071 (CORON-ACT)NCT04315480ChiCTR2000029765 tocilizumab
T531 5604-5625 Sentence denotes NCT04315298 sarilumab
T532 5626-5660 Sentence denotes NCT04310228 tocilizumabfavipiravir
T533 5661-5744 Sentence denotes NCT04306705 (TACOS) tocilizumabcontinuous renal replacement therapystandard of care
T534 5745-5808 Sentence denotes NCT04332094 (TOCOVID) tocilizumabazithromycinhydroxychloroquine
T535 5809-5876 Sentence denotes NCT04341870 (CORIMUNO-VIRO) sarilumabazithromycinhydroxychloroquine
T536 5877-5944 Sentence denotes NCT0433z638 (COV-AID) tocilizumabsiltuximabanakinrastandard of care
T537 5945-6185 Sentence denotes In addition to the IL-6 signaling pathway, other cytokine- and chemokine-associated elements, including IL-1R, GM-CSF, and the chemokine receptor CCR5, have been proposed as potential targets for blockade to manage COVID-19 CRS (Figure 6C).
T538 6186-6277 Sentence denotes Finally, complement activation was shown to be overactivated in lungs of COVID-19 patients.
T539 6278-6457 Sentence denotes Although results from the randomized trial are not yet published, anti-C5a monoclonal antibody therapy showed benefits in two critically ill COVID-19 patients (Gao et al., 2020d).