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LitCovid-PubTator

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T85","span":{"begin":339,"end":343},"obj":"Body_part"},{"id":"T86","span":{"begin":437,"end":445},"obj":"Body_part"},{"id":"T87","span":{"begin":499,"end":507},"obj":"Body_part"},{"id":"T88","span":{"begin":684,"end":695},"obj":"Body_part"},{"id":"T89","span":{"begin":697,"end":699},"obj":"Body_part"},{"id":"T90","span":{"begin":867,"end":872},"obj":"Body_part"}],"attributes":[{"id":"A85","pred":"fma_id","subj":"T85","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A86","pred":"fma_id","subj":"T86","obj":"http://purl.org/sig/ont/fma/fma67180"},{"id":"A87","pred":"fma_id","subj":"T87","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A88","pred":"fma_id","subj":"T88","obj":"http://purl.org/sig/ont/fma/fma86578"},{"id":"A89","pred":"fma_id","subj":"T89","obj":"http://purl.org/sig/ont/fma/fma86578"},{"id":"A90","pred":"fma_id","subj":"T90","obj":"http://purl.org/sig/ont/fma/fma67498"}],"text":"Question 3. should chloroquine/hydroxychloroquine be administered?\nThe rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects. With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]]. With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37]. However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38]. In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].\nRecently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries. They found 23 studies, all being conducted in China. However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2). In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.\nIn the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41]. In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls. Of note, six patients treated with hydroxychloroquine also received azithromycin. The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion. At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42]. Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43]. Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).\n\nQuestion 3 statement\nPending 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 function, 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."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T45","span":{"begin":867,"end":872},"obj":"Body_part"}],"attributes":[{"id":"A45","pred":"uberon_id","subj":"T45","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"}],"text":"Question 3. should chloroquine/hydroxychloroquine be administered?\nThe rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects. With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]]. With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37]. However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38]. In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].\nRecently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries. They found 23 studies, all being conducted in China. However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2). In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.\nIn the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41]. In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls. Of note, six patients treated with hydroxychloroquine also received azithromycin. The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion. At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42]. Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43]. Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).\n\nQuestion 3 statement\nPending 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 function, 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."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T86","span":{"begin":655,"end":660},"obj":"Phenotype"}],"attributes":[{"id":"A86","pred":"hp_id","subj":"T86","obj":"http://purl.obolibrary.org/obo/HP_0002664"}],"text":"Question 3. should chloroquine/hydroxychloroquine be administered?\nThe rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects. With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]]. With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37]. However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38]. In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].\nRecently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries. They found 23 studies, all being conducted in China. However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2). In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.\nIn the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41]. In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls. Of note, six patients treated with hydroxychloroquine also received azithromycin. The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion. At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42]. Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43]. Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).\n\nQuestion 3 statement\nPending 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 function, 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."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T15","span":{"begin":460,"end":491},"obj":"http://purl.obolibrary.org/obo/GO_0043687"},{"id":"T16","span":{"begin":661,"end":669},"obj":"http://purl.obolibrary.org/obo/GO_0070265"},{"id":"T17","span":{"begin":661,"end":669},"obj":"http://purl.obolibrary.org/obo/GO_0019835"},{"id":"T18","span":{"begin":661,"end":669},"obj":"http://purl.obolibrary.org/obo/GO_0008219"},{"id":"T19","span":{"begin":661,"end":669},"obj":"http://purl.obolibrary.org/obo/GO_0001906"}],"text":"Question 3. should chloroquine/hydroxychloroquine be administered?\nThe rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects. With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]]. With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37]. However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38]. In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].\nRecently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries. They found 23 studies, all being conducted in China. However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2). In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.\nIn the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41]. In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls. Of note, six patients treated with hydroxychloroquine also received azithromycin. The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion. At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42]. Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43]. Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).\n\nQuestion 3 statement\nPending 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 function, 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."}

LitCovid-sentences

2_test

{"project":"2_test","denotations":[{"id":"32360444-15351731-22369771","span":{"begin":557,"end":559},"obj":"15351731"},{"id":"32360444-32203437-22369772","span":{"begin":575,"end":577},"obj":"32203437"},{"id":"32360444-9002011-22369773","span":{"begin":922,"end":924},"obj":"9002011"},{"id":"32360444-32194152-22369774","span":{"begin":1304,"end":1306},"obj":"32194152"}],"text":"Question 3. should chloroquine/hydroxychloroquine be administered?\nThe rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects. With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]]. With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37]. However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38]. In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].\nRecently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries. They found 23 studies, all being conducted in China. However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2). In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.\nIn the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41]. In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls. Of note, six patients treated with hydroxychloroquine also received azithromycin. The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion. At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42]. Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43]. Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).\n\nQuestion 3 statement\nPending 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 function, 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."}

PMC:7195088 / 48271-53047 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7195088 / 48271-53047 JSON TXT