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LitCovid-sentences  

PMC:7252008 JSONTXT 17 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-3 Sentence denotes Re:
T2 4-87 Sentence denotes Patiently waiting for the results of anti-IL 6 therapy in severe COVID-19 infection
T3 89-101 Sentence denotes Dear Editor,
T4 102-283 Sentence denotes We thank Cunningham et al. [1] and Ruscitti et al. [2] for their commentary on our article [3] on the Macrophage activation syndrome (MAS)-like lung pathology in COVID-19 pneumonia.
T5 284-483 Sentence denotes In order to clarify the classification of MAS, we proposed two types of MAS that fit along the immunological disease continuum of inflammation against self; modified for loss or gain of function [4].
T6 484-769 Sentence denotes It may turn out that some of the hyper inflammation related features of COVID-19 are due to overzealous killing of virally infected cells by CD8+ cytotoxic T-cells and COVID-19 related antigen driven expansion of CD4+ helper T-cells with increased pro-inflammatory cytokine production.
T7 770-964 Sentence denotes Such a scenario would be analogous to the gain of function that occurs in adaptive immunity with chimeric antigen receptor (CAR)-T cells where the induced MAS can be treated with anti-IL-6R [3].
T8 965-1103 Sentence denotes This pattern of inflammation occurs in immunocompetent subjects and is also known as secondary haemophagocytic lymphohistiocytosis (sHLH).
T9 1104-1173 Sentence denotes To what degree this exists for COVID-19 infection awaits elucidation.
T10 1174-1314 Sentence denotes The scenario that Cunningham et al. [1] describe relates more to loss of function in the immune system or what is termed “perforinopathies”.
T11 1315-1577 Sentence denotes In Fig. 3A of our article [3] we included the monogenic perforinopathies where there may be complete absence of perforin pathway machinery and where failure to clear virus leads to T-cell expansion that drives macrophage activation in what is termed primary HLH.
T12 1578-1729 Sentence denotes Cunningham et al. [1] point out a scenario where high levels of IL-6 is associated with diminished T-cell perforin expression in experimental settings.
T13 1730-1869 Sentence denotes Therefore, it is suggested that anti-IL6R blockade may help augment cytotoxicity of CD8+ T-cells and NK-cells consequent to IL-6 reduction.
T14 1870-2000 Sentence denotes However, in other experimental studies IL-6 deficiency was associated with the different scenario of impaired viral clearance [5].
T15 2001-2171 Sentence denotes Given that the COVID-19 infection disables early type 1 interferon expression [6] then inhibition of the “second wave” of cytokines including IL-6 may be disadvantageous.
T16 2172-2435 Sentence denotes As summarized in our article, it is conceivable that the pleiotrophic actions of IL-6 in the context of pleiotrophic viral interactions with the immune system may actually favour viral persistence in some models where IL-6 level elevation could be beneficial [7].
T17 2436-2736 Sentence denotes Registry data from over 16,000 tocilizumab treated rheumatoid arthritis cases showed an increased risk of bacterial infection but no evidence for an increased risk of viral infection in humans, suggesting that IL-6 reduction is not linked to the emergence of previously known common viral infections.
T18 2737-2888 Sentence denotes Ruscitti et al. [2] also comment on the potential adverse role of IL-6 on lymphocyte mediated performin killing as summarized by Cunningham et al. [1].
T19 2889-3265 Sentence denotes Ruscitti et al. [2] prefer the “cytokine storm syndrome” over macrophage activation syndrome (MAS) and indeed we used the “cytokine storm syndrome” terminology within our article but went with “MAS-like” terminology overall As summarized above, we introduced a new concept for MAS classification as gain or loss in immune function that is very relevant for COVID-19 infection.
T20 3266-3383 Sentence denotes We also introduced the concept of a pulmonary intravascular coagulopathy secondary to the pulmonary MAS-like changes.
T21 3384-3461 Sentence denotes This is distinct from the disseminated intravascular coagulation seen in MAS.
T22 3462-3631 Sentence denotes The abundant monocytes and macrophages in the coronavirus family members like COVID-19 pneumonia certainly do not detract from the use of the terminology “MAS-like” [8].
T23 3632-4083 Sentence denotes .To conclude, we do not think that the lessons on the benefit of IL-6R antagonisms in CAR-T cell therapy or Stills disease, both in the setting of full immunocompetence, can be extrapolated to the severe COVID-19 pneumonia, in the setting of relative immunodeficiency, where vigorous cytokine response may be required to help control infection. The entire community awaits with baited breath in the hope that anti-cytokine therapy will be efficacious.
T24 4084-4355 Sentence denotes We hope that we have highlighted the recognition of a MAS-like lung pathology with secondary pulmonary intravascular coagulopathy and it is far from clear whether extrapolation from Rheumatology, Haematology or Immunology to the benefits of Anti-IL6R for COVID-19 exists.
T25 4357-4390 Sentence denotes Declaration of Competing Interest
T26 4391-4530 Sentence denotes Dennis McGonagle has received speaker fees and honoraria from Roche, Sobi and Novartis and research grants from 10.13039/100004336Novartis.