PMC:7195088 / 61276-65750 JSON TXT

Annnotations TAB JSON ListView MergeView

LitCovid-PubTator

LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T50","span":{"begin":1337,"end":1342},"obj":"Body_part"}],"attributes":[{"id":"A50","pred":"uberon_id","subj":"T50","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Question 6. should other immunosuppressive and/or immunomodulatory therapies be administered?\nAccording to some recent evidence, some patients with COVID-19 may develop secondary haemophagocytic lymphohistiocytosis, an underrecognized hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinaemia, with development of ARDS and multiorgan failure [46,47,67]. Consequently, immunosuppressive and/or immunomodulatory therapies have been proposed to contrast COVID-19–associated hyperinflammation.\nTocilizumab is a recombinant humanized monoclonal antibody inhibiting membrane-bound and soluble IL-6 receptors [68] and is currently approved for the treatment of patients with rheumatoid arthritis, giant-cell arteritis, juvenile idiopathic arthritis and patients with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome [68,69]. In this regard, tocilizumab may help mitigate the cytokine release syndrome by decreasing cytokine concentrations and acute-phase reactant production [70]. In a recent preprint paper, Xu et al. [71] reported their experience of treating 21 COVID-19 patients with tocilizumab. In their still-to-be-peer-reviewed case series, the following were observed after tocilizumab administration: (a) reduction in body temperature (21/21, 100%); (b) improved blood oxygenation (15/21, 71.4%); (c) normalization of lymphocyte count (10/17, 58.8%); (d) normalization of C-reactive protein (16/19, 82.4%); and (c) resolution of abnormalities on computed tomography (19/21, 90.5%). Interestingly, no adverse reactions were observed after tocilizumab administration, but long-term follow-up was not available. Tocilizumab has been deemed by Chinese National Health Commission to be a possible treatment option for patients with severe COVID-19 with elevated IL-6 [72]. The recommended dose is 4 to 8 mg/kg or 400 mg standard dose provided intravenously once, with the option to repeat a dose after 8 to 12 hours (not to exceed a total dose of 800 mg). However, it should be noted that the optimal time for administering tocilizumab has not yet been fully elucidated; nor is there a clear IL-6 threshold associated with progression to severe disease. At the time of writing, there are at least eight ongoing RCT evaluating the efficacy and safety of tocilizumab in COVID-19 patients (Table 2).\nOther immune-modulatory drugs including anakinra (interleukin 1 receptor antagonist) or Janus kinase family enzyme inhibitors have been proposed for the management of SARS-CoV-2–infected patients. Notably, there is currently no supporting clinical evidence, and RCT are ongoing (Table 2) [67,73].\nFinally, modifications of the immune response through administration of high-dose intravenous immunoglobulin or convalescent plasma have also been proposed or used in small case series, and they merit further investigation in dedicated RCT [[74], [75], [76], [77], [78]].\n\nQuestion 6 statement\nOwing to the lack of high-level evidence, administration of tocilizumab in patients with COVID-19 should preferentially occur within the framework of RCT. Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections). In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be fully aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series), and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.\nIn the absence of clinical studies, we suggest that also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) should be preferentially administered within RCT. This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in very small case series, both deserve dedicated RCT investigation to clearly understand their tolerability as well as the role they play in affecting COVID-19 outcomes."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T103","span":{"begin":694,"end":714},"obj":"Phenotype"},{"id":"T104","span":{"begin":727,"end":736},"obj":"Phenotype"},{"id":"T105","span":{"begin":738,"end":767},"obj":"Phenotype"},{"id":"T106","span":{"begin":854,"end":879},"obj":"Phenotype"},{"id":"T107","span":{"begin":939,"end":964},"obj":"Phenotype"}],"attributes":[{"id":"A103","pred":"hp_id","subj":"T103","obj":"http://purl.obolibrary.org/obo/HP_0001370"},{"id":"A104","pred":"hp_id","subj":"T104","obj":"http://purl.obolibrary.org/obo/HP_0012089"},{"id":"A105","pred":"hp_id","subj":"T105","obj":"http://purl.obolibrary.org/obo/HP_0005681"},{"id":"A106","pred":"hp_id","subj":"T106","obj":"http://purl.obolibrary.org/obo/HP_0033041"},{"id":"A107","pred":"hp_id","subj":"T107","obj":"http://purl.obolibrary.org/obo/HP_0033041"}],"text":"Question 6. should other immunosuppressive and/or immunomodulatory therapies be administered?\nAccording to some recent evidence, some patients with COVID-19 may develop secondary haemophagocytic lymphohistiocytosis, an underrecognized hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinaemia, with development of ARDS and multiorgan failure [46,47,67]. Consequently, immunosuppressive and/or immunomodulatory therapies have been proposed to contrast COVID-19–associated hyperinflammation.\nTocilizumab is a recombinant humanized monoclonal antibody inhibiting membrane-bound and soluble IL-6 receptors [68] and is currently approved for the treatment of patients with rheumatoid arthritis, giant-cell arteritis, juvenile idiopathic arthritis and patients with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome [68,69]. In this regard, tocilizumab may help mitigate the cytokine release syndrome by decreasing cytokine concentrations and acute-phase reactant production [70]. In a recent preprint paper, Xu et al. [71] reported their experience of treating 21 COVID-19 patients with tocilizumab. In their still-to-be-peer-reviewed case series, the following were observed after tocilizumab administration: (a) reduction in body temperature (21/21, 100%); (b) improved blood oxygenation (15/21, 71.4%); (c) normalization of lymphocyte count (10/17, 58.8%); (d) normalization of C-reactive protein (16/19, 82.4%); and (c) resolution of abnormalities on computed tomography (19/21, 90.5%). Interestingly, no adverse reactions were observed after tocilizumab administration, but long-term follow-up was not available. Tocilizumab has been deemed by Chinese National Health Commission to be a possible treatment option for patients with severe COVID-19 with elevated IL-6 [72]. The recommended dose is 4 to 8 mg/kg or 400 mg standard dose provided intravenously once, with the option to repeat a dose after 8 to 12 hours (not to exceed a total dose of 800 mg). However, it should be noted that the optimal time for administering tocilizumab has not yet been fully elucidated; nor is there a clear IL-6 threshold associated with progression to severe disease. At the time of writing, there are at least eight ongoing RCT evaluating the efficacy and safety of tocilizumab in COVID-19 patients (Table 2).\nOther immune-modulatory drugs including anakinra (interleukin 1 receptor antagonist) or Janus kinase family enzyme inhibitors have been proposed for the management of SARS-CoV-2–infected patients. Notably, there is currently no supporting clinical evidence, and RCT are ongoing (Table 2) [67,73].\nFinally, modifications of the immune response through administration of high-dose intravenous immunoglobulin or convalescent plasma have also been proposed or used in small case series, and they merit further investigation in dedicated RCT [[74], [75], [76], [77], [78]].\n\nQuestion 6 statement\nOwing to the lack of high-level evidence, administration of tocilizumab in patients with COVID-19 should preferentially occur within the framework of RCT. Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections). In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be fully aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series), and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.\nIn the absence of clinical studies, we suggest that also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) should be preferentially administered within RCT. This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in very small case series, both deserve dedicated RCT investigation to clearly understand their tolerability as well as the role they play in affecting COVID-19 outcomes."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T30","span":{"begin":2693,"end":2708},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T31","span":{"begin":4178,"end":4193},"obj":"http://purl.obolibrary.org/obo/GO_0006955"}],"text":"Question 6. should other immunosuppressive and/or immunomodulatory therapies be administered?\nAccording to some recent evidence, some patients with COVID-19 may develop secondary haemophagocytic lymphohistiocytosis, an underrecognized hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinaemia, with development of ARDS and multiorgan failure [46,47,67]. Consequently, immunosuppressive and/or immunomodulatory therapies have been proposed to contrast COVID-19–associated hyperinflammation.\nTocilizumab is a recombinant humanized monoclonal antibody inhibiting membrane-bound and soluble IL-6 receptors [68] and is currently approved for the treatment of patients with rheumatoid arthritis, giant-cell arteritis, juvenile idiopathic arthritis and patients with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome [68,69]. In this regard, tocilizumab may help mitigate the cytokine release syndrome by decreasing cytokine concentrations and acute-phase reactant production [70]. In a recent preprint paper, Xu et al. [71] reported their experience of treating 21 COVID-19 patients with tocilizumab. In their still-to-be-peer-reviewed case series, the following were observed after tocilizumab administration: (a) reduction in body temperature (21/21, 100%); (b) improved blood oxygenation (15/21, 71.4%); (c) normalization of lymphocyte count (10/17, 58.8%); (d) normalization of C-reactive protein (16/19, 82.4%); and (c) resolution of abnormalities on computed tomography (19/21, 90.5%). Interestingly, no adverse reactions were observed after tocilizumab administration, but long-term follow-up was not available. Tocilizumab has been deemed by Chinese National Health Commission to be a possible treatment option for patients with severe COVID-19 with elevated IL-6 [72]. The recommended dose is 4 to 8 mg/kg or 400 mg standard dose provided intravenously once, with the option to repeat a dose after 8 to 12 hours (not to exceed a total dose of 800 mg). However, it should be noted that the optimal time for administering tocilizumab has not yet been fully elucidated; nor is there a clear IL-6 threshold associated with progression to severe disease. At the time of writing, there are at least eight ongoing RCT evaluating the efficacy and safety of tocilizumab in COVID-19 patients (Table 2).\nOther immune-modulatory drugs including anakinra (interleukin 1 receptor antagonist) or Janus kinase family enzyme inhibitors have been proposed for the management of SARS-CoV-2–infected patients. Notably, there is currently no supporting clinical evidence, and RCT are ongoing (Table 2) [67,73].\nFinally, modifications of the immune response through administration of high-dose intravenous immunoglobulin or convalescent plasma have also been proposed or used in small case series, and they merit further investigation in dedicated RCT [[74], [75], [76], [77], [78]].\n\nQuestion 6 statement\nOwing to the lack of high-level evidence, administration of tocilizumab in patients with COVID-19 should preferentially occur within the framework of RCT. Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections). In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be fully aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series), and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.\nIn the absence of clinical studies, we suggest that also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) should be preferentially administered within RCT. This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in very small case series, both deserve dedicated RCT investigation to clearly understand their tolerability as well as the role they play in affecting COVID-19 outcomes."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T445","span":{"begin":0,"end":93},"obj":"Sentence"},{"id":"T446","span":{"begin":94,"end":379},"obj":"Sentence"},{"id":"T447","span":{"begin":380,"end":515},"obj":"Sentence"},{"id":"T448","span":{"begin":516,"end":888},"obj":"Sentence"},{"id":"T449","span":{"begin":889,"end":1044},"obj":"Sentence"},{"id":"T450","span":{"begin":1045,"end":1164},"obj":"Sentence"},{"id":"T451","span":{"begin":1165,"end":1555},"obj":"Sentence"},{"id":"T452","span":{"begin":1556,"end":1682},"obj":"Sentence"},{"id":"T453","span":{"begin":1683,"end":1841},"obj":"Sentence"},{"id":"T454","span":{"begin":1842,"end":2024},"obj":"Sentence"},{"id":"T455","span":{"begin":2025,"end":2222},"obj":"Sentence"},{"id":"T456","span":{"begin":2223,"end":2365},"obj":"Sentence"},{"id":"T457","span":{"begin":2366,"end":2562},"obj":"Sentence"},{"id":"T458","span":{"begin":2563,"end":2662},"obj":"Sentence"},{"id":"T459","span":{"begin":2663,"end":2934},"obj":"Sentence"},{"id":"T460","span":{"begin":2936,"end":2956},"obj":"Sentence"},{"id":"T461","span":{"begin":2957,"end":3111},"obj":"Sentence"},{"id":"T462","span":{"begin":3112,"end":3438},"obj":"Sentence"},{"id":"T463","span":{"begin":3439,"end":3915},"obj":"Sentence"},{"id":"T464","span":{"begin":3916,"end":4135},"obj":"Sentence"},{"id":"T465","span":{"begin":4136,"end":4474},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Question 6. should other immunosuppressive and/or immunomodulatory therapies be administered?\nAccording to some recent evidence, some patients with COVID-19 may develop secondary haemophagocytic lymphohistiocytosis, an underrecognized hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinaemia, with development of ARDS and multiorgan failure [46,47,67]. Consequently, immunosuppressive and/or immunomodulatory therapies have been proposed to contrast COVID-19–associated hyperinflammation.\nTocilizumab is a recombinant humanized monoclonal antibody inhibiting membrane-bound and soluble IL-6 receptors [68] and is currently approved for the treatment of patients with rheumatoid arthritis, giant-cell arteritis, juvenile idiopathic arthritis and patients with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome [68,69]. In this regard, tocilizumab may help mitigate the cytokine release syndrome by decreasing cytokine concentrations and acute-phase reactant production [70]. In a recent preprint paper, Xu et al. [71] reported their experience of treating 21 COVID-19 patients with tocilizumab. In their still-to-be-peer-reviewed case series, the following were observed after tocilizumab administration: (a) reduction in body temperature (21/21, 100%); (b) improved blood oxygenation (15/21, 71.4%); (c) normalization of lymphocyte count (10/17, 58.8%); (d) normalization of C-reactive protein (16/19, 82.4%); and (c) resolution of abnormalities on computed tomography (19/21, 90.5%). Interestingly, no adverse reactions were observed after tocilizumab administration, but long-term follow-up was not available. Tocilizumab has been deemed by Chinese National Health Commission to be a possible treatment option for patients with severe COVID-19 with elevated IL-6 [72]. The recommended dose is 4 to 8 mg/kg or 400 mg standard dose provided intravenously once, with the option to repeat a dose after 8 to 12 hours (not to exceed a total dose of 800 mg). However, it should be noted that the optimal time for administering tocilizumab has not yet been fully elucidated; nor is there a clear IL-6 threshold associated with progression to severe disease. At the time of writing, there are at least eight ongoing RCT evaluating the efficacy and safety of tocilizumab in COVID-19 patients (Table 2).\nOther immune-modulatory drugs including anakinra (interleukin 1 receptor antagonist) or Janus kinase family enzyme inhibitors have been proposed for the management of SARS-CoV-2–infected patients. Notably, there is currently no supporting clinical evidence, and RCT are ongoing (Table 2) [67,73].\nFinally, modifications of the immune response through administration of high-dose intravenous immunoglobulin or convalescent plasma have also been proposed or used in small case series, and they merit further investigation in dedicated RCT [[74], [75], [76], [77], [78]].\n\nQuestion 6 statement\nOwing to the lack of high-level evidence, administration of tocilizumab in patients with COVID-19 should preferentially occur within the framework of RCT. Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections). In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be fully aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series), and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.\nIn the absence of clinical studies, we suggest that also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) should be preferentially administered within RCT. This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in very small case series, both deserve dedicated RCT investigation to clearly understand their tolerability as well as the role they play in affecting COVID-19 outcomes."}

2_test

{"project":"2_test","denotations":[{"id":"32360444-32192578-22369810","span":{"begin":375,"end":377},"obj":"32192578"},{"id":"32360444-24834925-22369811","span":{"begin":629,"end":631},"obj":"24834925"},{"id":"32360444-24834925-22369812","span":{"begin":881,"end":883},"obj":"24834925"},{"id":"32360444-18358927-22369813","span":{"begin":884,"end":886},"obj":"18358927"},{"id":"32360444-32192578-22369814","span":{"begin":2655,"end":2657},"obj":"32192578"},{"id":"32360444-32032529-22369815","span":{"begin":2658,"end":2660},"obj":"32032529"},{"id":"32360444-32167489-22369816","span":{"begin":2905,"end":2907},"obj":"32167489"},{"id":"32360444-32258207-22369817","span":{"begin":2923,"end":2925},"obj":"32258207"},{"id":"32360444-32178711-22369818","span":{"begin":2929,"end":2931},"obj":"32178711"}],"text":"Question 6. should other immunosuppressive and/or immunomodulatory therapies be administered?\nAccording to some recent evidence, some patients with COVID-19 may develop secondary haemophagocytic lymphohistiocytosis, an underrecognized hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinaemia, with development of ARDS and multiorgan failure [46,47,67]. Consequently, immunosuppressive and/or immunomodulatory therapies have been proposed to contrast COVID-19–associated hyperinflammation.\nTocilizumab is a recombinant humanized monoclonal antibody inhibiting membrane-bound and soluble IL-6 receptors [68] and is currently approved for the treatment of patients with rheumatoid arthritis, giant-cell arteritis, juvenile idiopathic arthritis and patients with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome [68,69]. In this regard, tocilizumab may help mitigate the cytokine release syndrome by decreasing cytokine concentrations and acute-phase reactant production [70]. In a recent preprint paper, Xu et al. [71] reported their experience of treating 21 COVID-19 patients with tocilizumab. In their still-to-be-peer-reviewed case series, the following were observed after tocilizumab administration: (a) reduction in body temperature (21/21, 100%); (b) improved blood oxygenation (15/21, 71.4%); (c) normalization of lymphocyte count (10/17, 58.8%); (d) normalization of C-reactive protein (16/19, 82.4%); and (c) resolution of abnormalities on computed tomography (19/21, 90.5%). Interestingly, no adverse reactions were observed after tocilizumab administration, but long-term follow-up was not available. Tocilizumab has been deemed by Chinese National Health Commission to be a possible treatment option for patients with severe COVID-19 with elevated IL-6 [72]. The recommended dose is 4 to 8 mg/kg or 400 mg standard dose provided intravenously once, with the option to repeat a dose after 8 to 12 hours (not to exceed a total dose of 800 mg). However, it should be noted that the optimal time for administering tocilizumab has not yet been fully elucidated; nor is there a clear IL-6 threshold associated with progression to severe disease. At the time of writing, there are at least eight ongoing RCT evaluating the efficacy and safety of tocilizumab in COVID-19 patients (Table 2).\nOther immune-modulatory drugs including anakinra (interleukin 1 receptor antagonist) or Janus kinase family enzyme inhibitors have been proposed for the management of SARS-CoV-2–infected patients. Notably, there is currently no supporting clinical evidence, and RCT are ongoing (Table 2) [67,73].\nFinally, modifications of the immune response through administration of high-dose intravenous immunoglobulin or convalescent plasma have also been proposed or used in small case series, and they merit further investigation in dedicated RCT [[74], [75], [76], [77], [78]].\n\nQuestion 6 statement\nOwing to the lack of high-level evidence, administration of tocilizumab in patients with COVID-19 should preferentially occur within the framework of RCT. Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections). In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be fully aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series), and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.\nIn the absence of clinical studies, we suggest that also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) should be preferentially administered within RCT. This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in very small case series, both deserve dedicated RCT investigation to clearly understand their tolerability as well as the role they play in affecting COVID-19 outcomes."}

PMC:7195088 / 61276-65750 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7195088 / 61276-65750 JSON TXT