LitCovid-sentences  

PMC:7324763 / 54093-57940 JSONTXT 14 Projects

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Id Subject Object Predicate Lexical cue
T333 0-31 Sentence denotes Interferon Therapy and NK Cells
T334 32-213 Sentence denotes The importance of the interferon pathway is underscored by the fact that many viruses actively interfere with host interferon responses, for which coronaviruses are a prime example.
T335 214-334 Sentence denotes As described above, CoVs utilize numerous tactics to avoid elimination by disrupting the host type I IFN response (174).
T336 335-509 Sentence denotes Therefore, since the majority of CoVs fail to induce any detectable type I IFN response, eliciting a type I IFN response is a very attractive therapeutic strategy (118, 175).
T337 510-716 Sentence denotes Given the robust immunomodulatory nature of type I IFNs, uninfected or early symptomatic patients would benefit the most from this therapy to prevent exacerbating immunopathology at later stages of disease.
T338 717-798 Sentence denotes Numerous clinical trials have been initiated investigating type I IFNs (Table 1).
T339 799-1019 Sentence denotes A large study (NCT04320238) of ~3,000 medical staff allocated participants to two trial arms: (i) low-risk (non-isolated wards or laboratories) or (ii) high-risk (isolated wards in direct contact with COVID-19 patients).
T340 1020-1213 Sentence denotes In addition to the IFN-α-1b nasal drops, high-risk medical staff will also receive the immune-modulating TLR activator, thymosin α1, which indirectly activates NK cells through pDCs (176, 177).
T341 1214-1368 Sentence denotes Interestingly, reports in SARS-CoV-1 studies showed that IFN-β therapy had a 50-fold greater anti-viral activity in Vero cells than IFN-α treatment (178).
T342 1369-1849 Sentence denotes Promising results have been published from a Phase II study (NCT04276688) (179), showing that complementing lopinavir-ritonavir and ribavirin with subcutaneous IFN-β-1b in mild-to-moderate COVID-19 patients is safe with no serious adverse events reported in the triple combination therapy group, and highly effective, with significant and clinically meaningful reductions in time to complete alleviation of symptoms, hospital length of stay, and time to negative viral load (179).
T343 1850-2100 Sentence denotes Despite our best efforts in timing type I IFN therapy to mitigate immunopathology, these treatments still increase the risk of excessive activation of proinflammatory signals, which could damage host tissues and perpetuate immunopathology (180, 181).
T344 2101-2205 Sentence denotes For this reason, alternative therapeutic avenues to direct type I IFN administration are being explored.
T345 2206-2372 Sentence denotes Type III IFNs can be a valid alternative to type I IFNs, because they maintain antiviral functions yet are less toxic and less prone to mediate immunopathology (182).
T346 2373-2551 Sentence denotes The type III IFN, IFN-λ, activates NK cells indirectly (compared to type I IFNs which directly act on NK cells), resulting in a less potent and slower immune response (183, 184).
T347 2552-2674 Sentence denotes IFN-λ activates NK cells by stimulating macrophages to produce IL-12 which in turn induce NK cells to produce IFN-γ (185).
T348 2675-2809 Sentence denotes Pegylated IFN-λ is being tested in COVID-19 positive patients with mild symptoms in the absence of respiratory distress (NCT04331899).
T349 2810-2992 Sentence denotes While IFN-λ can lead to the eventual activation of NK cells, its primary utility is in preventing the tissue damaging potential of neutrophils at mucosal surfaces, such as the lungs.
T350 2993-3179 Sentence denotes However, IFN-λ also has been shown to reduce the rate of tissue repair, which in the context of COVID-19 which has a long disease course, could mean greater risk of secondary infections.
T351 3180-3424 Sentence denotes Since exogenous administration of any IFN therapy poses the risk of tipping the balance toward severe COVID-19 immunopathology, Broggi et al. assessed the levels of IFNs in upper and lower respiratory samples from healthy and COVID-19 patients.
T352 3425-3683 Sentence denotes In this preprint, they report that while the upper airway swabs showed similar mRNA expression levels of type I and III IFN compared to healthy controls, the BALF samples of severe COVID-19 patients had significantly elevated type I and III IFN levels (186).
T353 3684-3847 Sentence denotes Therefore, as with all of the therapies discussed in this review, careful consideration about safe and effective timing should guide our design of clinical trials.