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LitCovid-PubTator

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T1","span":{"begin":4496,"end":4504},"obj":"Body_part"},{"id":"T2","span":{"begin":4513,"end":4517},"obj":"Body_part"},{"id":"T3","span":{"begin":6460,"end":6475},"obj":"Body_part"},{"id":"T4","span":{"begin":6479,"end":6485},"obj":"Body_part"},{"id":"T5","span":{"begin":7033,"end":7037},"obj":"Body_part"},{"id":"T6","span":{"begin":8912,"end":8916},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"fma_id","subj":"T1","obj":"http://purl.org/sig/ont/fma/fma84050"},{"id":"A2","pred":"fma_id","subj":"T2","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A3","pred":"fma_id","subj":"T3","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A4","pred":"fma_id","subj":"T4","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A5","pred":"fma_id","subj":"T5","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma7195"}],"text":"Question Statement\nQuestion 1. How to use at best oxygen therapy and noninvasive mechanical ventilation for preventing intubation? Supplementary oxygen should be administered to patients with hypoxic respiratory failure for avoiding values of Spo2 lower than 90% and it should be aimed at reaching values not higher than 96%. Although still without firm evidence, we currently support the use of CPAP helmet (with gentle ventilation and a PEEP of no more than 10–12 cm of water) if the patient does not respond to standard/HFNC oxygen supplementation and there is no urgent indication for endotracheal intubation (expert opinion). However, no clear indications/criteria can be provided pending further experience. Finally, it should be kept in mind that patients with COVID-19 can get worse in a few hours, so they should be carefully monitored for worsening respiratory function for rapidly prompting tracheal intubation and mechanical ventilation.\nQuestion 2. Should antiviral agents be administered? At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients. This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available. Although promising in preclinical studies, remdesivir should be currently provided to COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature. Pending high-level supporting evidence, favipiravir and umifenovir should not be provided an outside RCT, at least in those countries where they are not approved for other indications. Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.\nQuestion 3. Should chloroquine/hydroxychloroquine be administered? Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic, renal function and QT prolongation. This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled, nonrandomized study. However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality. For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies. When this is unfeasible, off-label use may be considered according to local protocols and consent procedures. In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies. The same applies to prophylactic use.\nQuestion 4. Should antibiotics be administered? In our opinion, it might be prudent to consider empiric antibiotic treatment in critically ill patients with pneumonia due to COVID-19 in whom bacterial infection cannot be excluded. This suggestion is based on the fact that bacterial coinfection (a) is common in patients with viral pneumonia and (b) can be associated with a substantial risk of delaying appropriate treatment, thereby potentially increasing mortality. Because of the limited available data on both the microbiologic epidemiology (and the prevalence of antimicrobial resistance) of bacterial superinfections in COVID-19 patients, it is difficult to provide specific pathogen-oriented recommendations. Therefore, pending further studies, we suggest to empirically treat COVID-19 patients according to their clinical syndrome (e.g. community-acquired pneumonia, hospital-acquired pneumonia), choosing the best antimicrobial agent or agents on the basis of local guidelines and local antibiotic susceptibility patterns, with early de-escalation or discontinuation according to microbiology results, whenever available.\nQuestion 5. Should steroids be administered? So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection. As the WHO underlines, there is an important need for efficacy data from RCT for supporting corticosteroid therapy in patients with SARS-Cov-2. However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for rapidly progressive pneumonia and clinical deterioration in COVID-19 patients, we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission). Yet in the absence of convincing evidence, the following cannot currently be supported: (1) steroid administration stratified according to inflammatory markers; and (b) steroid administration in non–critically ill COVID-19 patients.\nQuestion 6. Should other immunosuppressive and/or immunomodulatory therapies be administered? Owing to the lack of high-level evidence, administration of tocilizumab to 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 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. In the absence of clinical studies, we suggest to preferentially administer also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) 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 small case series, both deserve dedicated RCT investigation to clearly understand their role in impacting COVID-19 outcomes and their tolerability.\nQuestion 7. What is the optimal timing of treatment initiation? Supportive therapy (symptomatic therapy, rehydration and oxygen supplementation, if necessary), should be initiated as soon as the patient manifests respiratory or systemic symptoms, including severe asthenia, high fever, persistent cough and/or clinical or radiologic signs of lung involvement. Pending further evidence, in our opinion, antiviral treatments should not be provided to patients with SARS-CoV-2 infection outside RCT or compassionate-use programmes (with the exception of early oseltamivir initiation in patients with suspected concomitant influenza). Corticosteroids should be provided early in well-defined categories of patients (patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections), while their role in other COVID-19 patients still remains uncertain. Although based on low-level evidence and pending RCT results, in our opinion, early hydroxychloroquine administration may be considered in COVID-19 patients manifesting moderate to severe symptoms, whereas further data are needed to better delineate the true balance between possible favourable effects and toxicity of hydroxychloroquine in mildly symptomatic and asymptomatic patients.\nQuestion 8. What is the optimal treatment duration? Chloroquine/hydroxychloroquine treatment should be continued for at least 5 days, and possibly up to 20 days, according to some expert opinions, although it should be noted that data regarding the relative safety of different lengths of administration in COVID-19 patients are currently unavailable. Early discontinuation should be considered in the presence of adverse effects (e.g. QT prolongation or hepatic/renal toxicity). If the administration of remdesivir is approved within compassionate-use/expanded-access programmes, treatment duration should follow compassionate or expanded access protocols (e.g. up to 10 days according to the most recent compassionate protocol at the time of this review). If corticosteroids are provided, we suggest a total treatment duration of 7–10 days, with progressive dose reduction. If the patient's condition deteriorates with worsening lung physiology after withdrawal of steroid treatment in the absence of bacterial or fungal superinfection, a second course of corticosteroid treatment may be considered, followed by slow tapering after improvement."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T1","span":{"begin":4513,"end":4517},"obj":"Body_part"},{"id":"T2","span":{"begin":6904,"end":6927},"obj":"Body_part"},{"id":"T3","span":{"begin":7033,"end":7037},"obj":"Body_part"},{"id":"T4","span":{"begin":8912,"end":8916},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001004"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Question Statement\nQuestion 1. How to use at best oxygen therapy and noninvasive mechanical ventilation for preventing intubation? Supplementary oxygen should be administered to patients with hypoxic respiratory failure for avoiding values of Spo2 lower than 90% and it should be aimed at reaching values not higher than 96%. Although still without firm evidence, we currently support the use of CPAP helmet (with gentle ventilation and a PEEP of no more than 10–12 cm of water) if the patient does not respond to standard/HFNC oxygen supplementation and there is no urgent indication for endotracheal intubation (expert opinion). However, no clear indications/criteria can be provided pending further experience. Finally, it should be kept in mind that patients with COVID-19 can get worse in a few hours, so they should be carefully monitored for worsening respiratory function for rapidly prompting tracheal intubation and mechanical ventilation.\nQuestion 2. Should antiviral agents be administered? At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients. This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available. Although promising in preclinical studies, remdesivir should be currently provided to COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature. Pending high-level supporting evidence, favipiravir and umifenovir should not be provided an outside RCT, at least in those countries where they are not approved for other indications. Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.\nQuestion 3. Should chloroquine/hydroxychloroquine be administered? Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic, renal function and QT prolongation. This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled, nonrandomized study. However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality. For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies. When this is unfeasible, off-label use may be considered according to local protocols and consent procedures. In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies. The same applies to prophylactic use.\nQuestion 4. Should antibiotics be administered? In our opinion, it might be prudent to consider empiric antibiotic treatment in critically ill patients with pneumonia due to COVID-19 in whom bacterial infection cannot be excluded. This suggestion is based on the fact that bacterial coinfection (a) is common in patients with viral pneumonia and (b) can be associated with a substantial risk of delaying appropriate treatment, thereby potentially increasing mortality. Because of the limited available data on both the microbiologic epidemiology (and the prevalence of antimicrobial resistance) of bacterial superinfections in COVID-19 patients, it is difficult to provide specific pathogen-oriented recommendations. Therefore, pending further studies, we suggest to empirically treat COVID-19 patients according to their clinical syndrome (e.g. community-acquired pneumonia, hospital-acquired pneumonia), choosing the best antimicrobial agent or agents on the basis of local guidelines and local antibiotic susceptibility patterns, with early de-escalation or discontinuation according to microbiology results, whenever available.\nQuestion 5. Should steroids be administered? So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection. As the WHO underlines, there is an important need for efficacy data from RCT for supporting corticosteroid therapy in patients with SARS-Cov-2. However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for rapidly progressive pneumonia and clinical deterioration in COVID-19 patients, we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission). Yet in the absence of convincing evidence, the following cannot currently be supported: (1) steroid administration stratified according to inflammatory markers; and (b) steroid administration in non–critically ill COVID-19 patients.\nQuestion 6. Should other immunosuppressive and/or immunomodulatory therapies be administered? Owing to the lack of high-level evidence, administration of tocilizumab to 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 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. In the absence of clinical studies, we suggest to preferentially administer also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) 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 small case series, both deserve dedicated RCT investigation to clearly understand their role in impacting COVID-19 outcomes and their tolerability.\nQuestion 7. What is the optimal timing of treatment initiation? Supportive therapy (symptomatic therapy, rehydration and oxygen supplementation, if necessary), should be initiated as soon as the patient manifests respiratory or systemic symptoms, including severe asthenia, high fever, persistent cough and/or clinical or radiologic signs of lung involvement. Pending further evidence, in our opinion, antiviral treatments should not be provided to patients with SARS-CoV-2 infection outside RCT or compassionate-use programmes (with the exception of early oseltamivir initiation in patients with suspected concomitant influenza). Corticosteroids should be provided early in well-defined categories of patients (patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections), while their role in other COVID-19 patients still remains uncertain. Although based on low-level evidence and pending RCT results, in our opinion, early hydroxychloroquine administration may be considered in COVID-19 patients manifesting moderate to severe symptoms, whereas further data are needed to better delineate the true balance between possible favourable effects and toxicity of hydroxychloroquine in mildly symptomatic and asymptomatic patients.\nQuestion 8. What is the optimal treatment duration? Chloroquine/hydroxychloroquine treatment should be continued for at least 5 days, and possibly up to 20 days, according to some expert opinions, although it should be noted that data regarding the relative safety of different lengths of administration in COVID-19 patients are currently unavailable. Early discontinuation should be considered in the presence of adverse effects (e.g. QT prolongation or hepatic/renal toxicity). If the administration of remdesivir is approved within compassionate-use/expanded-access programmes, treatment duration should follow compassionate or expanded access protocols (e.g. up to 10 days according to the most recent compassionate protocol at the time of this review). If corticosteroids are provided, we suggest a total treatment duration of 7–10 days, with progressive dose reduction. If the patient's condition deteriorates with worsening lung physiology after withdrawal of steroid treatment in the absence of bacterial or fungal superinfection, a second course of corticosteroid treatment may be considered, followed by slow tapering after improvement."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T3","span":{"begin":200,"end":219},"obj":"Phenotype"},{"id":"T4","span":{"begin":3122,"end":3131},"obj":"Phenotype"},{"id":"T5","span":{"begin":3297,"end":3306},"obj":"Phenotype"},{"id":"T6","span":{"begin":3830,"end":3839},"obj":"Phenotype"},{"id":"T7","span":{"begin":3859,"end":3868},"obj":"Phenotype"},{"id":"T8","span":{"begin":4570,"end":4579},"obj":"Phenotype"},{"id":"T9","span":{"begin":4784,"end":4803},"obj":"Phenotype"},{"id":"T10","span":{"begin":6955,"end":6963},"obj":"Phenotype"},{"id":"T11","span":{"begin":6970,"end":6975},"obj":"Phenotype"},{"id":"T12","span":{"begin":6988,"end":6993},"obj":"Phenotype"},{"id":"T13","span":{"begin":7452,"end":7471},"obj":"Phenotype"}],"attributes":[{"id":"A3","pred":"hp_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/HP_0002878"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A8","pred":"hp_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/HP_0002878"},{"id":"A10","pred":"hp_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/HP_0025406"},{"id":"A11","pred":"hp_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/HP_0001945"},{"id":"A12","pred":"hp_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/HP_0012735"},{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0002878"}],"text":"Question Statement\nQuestion 1. How to use at best oxygen therapy and noninvasive mechanical ventilation for preventing intubation? Supplementary oxygen should be administered to patients with hypoxic respiratory failure for avoiding values of Spo2 lower than 90% and it should be aimed at reaching values not higher than 96%. Although still without firm evidence, we currently support the use of CPAP helmet (with gentle ventilation and a PEEP of no more than 10–12 cm of water) if the patient does not respond to standard/HFNC oxygen supplementation and there is no urgent indication for endotracheal intubation (expert opinion). However, no clear indications/criteria can be provided pending further experience. Finally, it should be kept in mind that patients with COVID-19 can get worse in a few hours, so they should be carefully monitored for worsening respiratory function for rapidly prompting tracheal intubation and mechanical ventilation.\nQuestion 2. Should antiviral agents be administered? At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients. This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available. Although promising in preclinical studies, remdesivir should be currently provided to COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature. Pending high-level supporting evidence, favipiravir and umifenovir should not be provided an outside RCT, at least in those countries where they are not approved for other indications. Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.\nQuestion 3. Should chloroquine/hydroxychloroquine be administered? Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic, renal function and QT prolongation. This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled, nonrandomized study. However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality. For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies. When this is unfeasible, off-label use may be considered according to local protocols and consent procedures. In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies. The same applies to prophylactic use.\nQuestion 4. Should antibiotics be administered? In our opinion, it might be prudent to consider empiric antibiotic treatment in critically ill patients with pneumonia due to COVID-19 in whom bacterial infection cannot be excluded. This suggestion is based on the fact that bacterial coinfection (a) is common in patients with viral pneumonia and (b) can be associated with a substantial risk of delaying appropriate treatment, thereby potentially increasing mortality. Because of the limited available data on both the microbiologic epidemiology (and the prevalence of antimicrobial resistance) of bacterial superinfections in COVID-19 patients, it is difficult to provide specific pathogen-oriented recommendations. Therefore, pending further studies, we suggest to empirically treat COVID-19 patients according to their clinical syndrome (e.g. community-acquired pneumonia, hospital-acquired pneumonia), choosing the best antimicrobial agent or agents on the basis of local guidelines and local antibiotic susceptibility patterns, with early de-escalation or discontinuation according to microbiology results, whenever available.\nQuestion 5. Should steroids be administered? So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection. As the WHO underlines, there is an important need for efficacy data from RCT for supporting corticosteroid therapy in patients with SARS-Cov-2. However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for rapidly progressive pneumonia and clinical deterioration in COVID-19 patients, we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission). Yet in the absence of convincing evidence, the following cannot currently be supported: (1) steroid administration stratified according to inflammatory markers; and (b) steroid administration in non–critically ill COVID-19 patients.\nQuestion 6. Should other immunosuppressive and/or immunomodulatory therapies be administered? Owing to the lack of high-level evidence, administration of tocilizumab to 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 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. In the absence of clinical studies, we suggest to preferentially administer also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) 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 small case series, both deserve dedicated RCT investigation to clearly understand their role in impacting COVID-19 outcomes and their tolerability.\nQuestion 7. What is the optimal timing of treatment initiation? Supportive therapy (symptomatic therapy, rehydration and oxygen supplementation, if necessary), should be initiated as soon as the patient manifests respiratory or systemic symptoms, including severe asthenia, high fever, persistent cough and/or clinical or radiologic signs of lung involvement. Pending further evidence, in our opinion, antiviral treatments should not be provided to patients with SARS-CoV-2 infection outside RCT or compassionate-use programmes (with the exception of early oseltamivir initiation in patients with suspected concomitant influenza). Corticosteroids should be provided early in well-defined categories of patients (patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections), while their role in other COVID-19 patients still remains uncertain. Although based on low-level evidence and pending RCT results, in our opinion, early hydroxychloroquine administration may be considered in COVID-19 patients manifesting moderate to severe symptoms, whereas further data are needed to better delineate the true balance between possible favourable effects and toxicity of hydroxychloroquine in mildly symptomatic and asymptomatic patients.\nQuestion 8. What is the optimal treatment duration? Chloroquine/hydroxychloroquine treatment should be continued for at least 5 days, and possibly up to 20 days, according to some expert opinions, although it should be noted that data regarding the relative safety of different lengths of administration in COVID-19 patients are currently unavailable. Early discontinuation should be considered in the presence of adverse effects (e.g. QT prolongation or hepatic/renal toxicity). If the administration of remdesivir is approved within compassionate-use/expanded-access programmes, treatment duration should follow compassionate or expanded access protocols (e.g. up to 10 days according to the most recent compassionate protocol at the time of this review). If corticosteroids are provided, we suggest a total treatment duration of 7–10 days, with progressive dose reduction. If the patient's condition deteriorates with worsening lung physiology after withdrawal of steroid treatment in the absence of bacterial or fungal superinfection, a second course of corticosteroid treatment may be considered, followed by slow tapering after improvement."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T1","span":{"begin":4479,"end":4491},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T2","span":{"begin":6414,"end":6429},"obj":"http://purl.obolibrary.org/obo/GO_0006955"}],"text":"Question Statement\nQuestion 1. How to use at best oxygen therapy and noninvasive mechanical ventilation for preventing intubation? Supplementary oxygen should be administered to patients with hypoxic respiratory failure for avoiding values of Spo2 lower than 90% and it should be aimed at reaching values not higher than 96%. Although still without firm evidence, we currently support the use of CPAP helmet (with gentle ventilation and a PEEP of no more than 10–12 cm of water) if the patient does not respond to standard/HFNC oxygen supplementation and there is no urgent indication for endotracheal intubation (expert opinion). However, no clear indications/criteria can be provided pending further experience. Finally, it should be kept in mind that patients with COVID-19 can get worse in a few hours, so they should be carefully monitored for worsening respiratory function for rapidly prompting tracheal intubation and mechanical ventilation.\nQuestion 2. Should antiviral agents be administered? At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients. This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available. Although promising in preclinical studies, remdesivir should be currently provided to COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature. Pending high-level supporting evidence, favipiravir and umifenovir should not be provided an outside RCT, at least in those countries where they are not approved for other indications. Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.\nQuestion 3. Should chloroquine/hydroxychloroquine be administered? Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic, renal function and QT prolongation. This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled, nonrandomized study. However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality. For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies. When this is unfeasible, off-label use may be considered according to local protocols and consent procedures. In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies. The same applies to prophylactic use.\nQuestion 4. Should antibiotics be administered? In our opinion, it might be prudent to consider empiric antibiotic treatment in critically ill patients with pneumonia due to COVID-19 in whom bacterial infection cannot be excluded. This suggestion is based on the fact that bacterial coinfection (a) is common in patients with viral pneumonia and (b) can be associated with a substantial risk of delaying appropriate treatment, thereby potentially increasing mortality. Because of the limited available data on both the microbiologic epidemiology (and the prevalence of antimicrobial resistance) of bacterial superinfections in COVID-19 patients, it is difficult to provide specific pathogen-oriented recommendations. Therefore, pending further studies, we suggest to empirically treat COVID-19 patients according to their clinical syndrome (e.g. community-acquired pneumonia, hospital-acquired pneumonia), choosing the best antimicrobial agent or agents on the basis of local guidelines and local antibiotic susceptibility patterns, with early de-escalation or discontinuation according to microbiology results, whenever available.\nQuestion 5. Should steroids be administered? So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection. As the WHO underlines, there is an important need for efficacy data from RCT for supporting corticosteroid therapy in patients with SARS-Cov-2. However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for rapidly progressive pneumonia and clinical deterioration in COVID-19 patients, we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission). Yet in the absence of convincing evidence, the following cannot currently be supported: (1) steroid administration stratified according to inflammatory markers; and (b) steroid administration in non–critically ill COVID-19 patients.\nQuestion 6. Should other immunosuppressive and/or immunomodulatory therapies be administered? Owing to the lack of high-level evidence, administration of tocilizumab to 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 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. In the absence of clinical studies, we suggest to preferentially administer also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) 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 small case series, both deserve dedicated RCT investigation to clearly understand their role in impacting COVID-19 outcomes and their tolerability.\nQuestion 7. What is the optimal timing of treatment initiation? Supportive therapy (symptomatic therapy, rehydration and oxygen supplementation, if necessary), should be initiated as soon as the patient manifests respiratory or systemic symptoms, including severe asthenia, high fever, persistent cough and/or clinical or radiologic signs of lung involvement. Pending further evidence, in our opinion, antiviral treatments should not be provided to patients with SARS-CoV-2 infection outside RCT or compassionate-use programmes (with the exception of early oseltamivir initiation in patients with suspected concomitant influenza). Corticosteroids should be provided early in well-defined categories of patients (patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections), while their role in other COVID-19 patients still remains uncertain. Although based on low-level evidence and pending RCT results, in our opinion, early hydroxychloroquine administration may be considered in COVID-19 patients manifesting moderate to severe symptoms, whereas further data are needed to better delineate the true balance between possible favourable effects and toxicity of hydroxychloroquine in mildly symptomatic and asymptomatic patients.\nQuestion 8. What is the optimal treatment duration? Chloroquine/hydroxychloroquine treatment should be continued for at least 5 days, and possibly up to 20 days, according to some expert opinions, although it should be noted that data regarding the relative safety of different lengths of administration in COVID-19 patients are currently unavailable. Early discontinuation should be considered in the presence of adverse effects (e.g. QT prolongation or hepatic/renal toxicity). If the administration of remdesivir is approved within compassionate-use/expanded-access programmes, treatment duration should follow compassionate or expanded access protocols (e.g. up to 10 days according to the most recent compassionate protocol at the time of this review). If corticosteroids are provided, we suggest a total treatment duration of 7–10 days, with progressive dose reduction. If the patient's condition deteriorates with worsening lung physiology after withdrawal of steroid treatment in the absence of bacterial or fungal superinfection, a second course of corticosteroid treatment may be considered, followed by slow tapering after improvement."}

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