PMC:7441788 / 39140-42371 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T128","span":{"begin":367,"end":375},"obj":"Body_part"},{"id":"T129","span":{"begin":1105,"end":1109},"obj":"Body_part"},{"id":"T130","span":{"begin":2372,"end":2376},"obj":"Body_part"}],"attributes":[{"id":"A128","pred":"fma_id","subj":"T128","obj":"http://purl.org/sig/ont/fma/fma67180"},{"id":"A129","pred":"fma_id","subj":"T129","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A130","pred":"fma_id","subj":"T130","obj":"http://purl.org/sig/ont/fma/fma62100"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T23","span":{"begin":2372,"end":2376},"obj":"Body_part"}],"attributes":[{"id":"A23","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0001913"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T159","span":{"begin":16,"end":24},"obj":"Disease"},{"id":"T160","span":{"begin":244,"end":252},"obj":"Disease"},{"id":"T161","span":{"begin":541,"end":549},"obj":"Disease"},{"id":"T162","span":{"begin":657,"end":665},"obj":"Disease"},{"id":"T163","span":{"begin":693,"end":701},"obj":"Disease"},{"id":"T164","span":{"begin":796,"end":804},"obj":"Disease"},{"id":"T165","span":{"begin":903,"end":911},"obj":"Disease"},{"id":"T166","span":{"begin":1081,"end":1086},"obj":"Disease"},{"id":"T167","span":{"begin":1229,"end":1240},"obj":"Disease"},{"id":"T168","span":{"begin":1296,"end":1305},"obj":"Disease"},{"id":"T169","span":{"begin":1443,"end":1451},"obj":"Disease"},{"id":"T170","span":{"begin":1489,"end":1497},"obj":"Disease"},{"id":"T171","span":{"begin":1867,"end":1875},"obj":"Disease"},{"id":"T172","span":{"begin":2143,"end":2151},"obj":"Disease"},{"id":"T173","span":{"begin":2457,"end":2465},"obj":"Disease"},{"id":"T174","span":{"begin":2468,"end":2477},"obj":"Disease"},{"id":"T175","span":{"begin":2857,"end":2865},"obj":"Disease"},{"id":"T176","span":{"begin":2992,"end":3000},"obj":"Disease"},{"id":"T177","span":{"begin":3116,"end":3124},"obj":"Disease"}],"attributes":[{"id":"A159","pred":"mondo_id","subj":"T159","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A160","pred":"mondo_id","subj":"T160","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A161","pred":"mondo_id","subj":"T161","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A162","pred":"mondo_id","subj":"T162","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A163","pred":"mondo_id","subj":"T163","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A164","pred":"mondo_id","subj":"T164","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A165","pred":"mondo_id","subj":"T165","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A166","pred":"mondo_id","subj":"T166","obj":"http://purl.obolibrary.org/obo/MONDO_0005737"},{"id":"A167","pred":"mondo_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/MONDO_0017941"},{"id":"A168","pred":"mondo_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A169","pred":"mondo_id","subj":"T169","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A170","pred":"mondo_id","subj":"T170","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A171","pred":"mondo_id","subj":"T171","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A172","pred":"mondo_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A173","pred":"mondo_id","subj":"T173","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A174","pred":"mondo_id","subj":"T174","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A175","pred":"mondo_id","subj":"T175","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A176","pred":"mondo_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A177","pred":"mondo_id","subj":"T177","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T285","span":{"begin":188,"end":198},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T286","span":{"begin":408,"end":416},"obj":"http://purl.obolibrary.org/obo/UBERON_0000158"},{"id":"T287","span":{"begin":454,"end":462},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T288","span":{"begin":517,"end":518},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T289","span":{"begin":551,"end":552},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T290","span":{"begin":708,"end":710},"obj":"http://purl.obolibrary.org/obo/CLO_0050510"},{"id":"T291","span":{"begin":769,"end":777},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T292","span":{"begin":1087,"end":1092},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T293","span":{"begin":1093,"end":1109},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T294","span":{"begin":1153,"end":1159},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T295","span":{"begin":1192,"end":1195},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T296","span":{"begin":1241,"end":1246},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T297","span":{"begin":1264,"end":1270},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T298","span":{"begin":1832,"end":1834},"obj":"http://purl.obolibrary.org/obo/CLO_0050510"},{"id":"T299","span":{"begin":1837,"end":1838},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T300","span":{"begin":2267,"end":2268},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T301","span":{"begin":2324,"end":2332},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T302","span":{"begin":2395,"end":2401},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T303","span":{"begin":2626,"end":2631},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T304","span":{"begin":2766,"end":2767},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T409","span":{"begin":157,"end":159},"obj":"Chemical"},{"id":"T410","span":{"begin":310,"end":312},"obj":"Chemical"},{"id":"T411","span":{"begin":599,"end":601},"obj":"Chemical"},{"id":"T412","span":{"begin":781,"end":783},"obj":"Chemical"},{"id":"T413","span":{"begin":857,"end":859},"obj":"Chemical"},{"id":"T414","span":{"begin":1069,"end":1071},"obj":"Chemical"},{"id":"T415","span":{"begin":1189,"end":1191},"obj":"Chemical"},{"id":"T416","span":{"begin":1466,"end":1468},"obj":"Chemical"},{"id":"T417","span":{"begin":2196,"end":2198},"obj":"Chemical"},{"id":"T418","span":{"begin":2294,"end":2296},"obj":"Chemical"},{"id":"T419","span":{"begin":2419,"end":2421},"obj":"Chemical"},{"id":"T420","span":{"begin":2595,"end":2607},"obj":"Chemical"},{"id":"T421","span":{"begin":2730,"end":2732},"obj":"Chemical"},{"id":"T422","span":{"begin":2768,"end":2777},"obj":"Chemical"},{"id":"T423","span":{"begin":2968,"end":2970},"obj":"Chemical"},{"id":"T424","span":{"begin":3048,"end":3059},"obj":"Chemical"},{"id":"T425","span":{"begin":3063,"end":3065},"obj":"Chemical"},{"id":"T426","span":{"begin":3106,"end":3111},"obj":"Chemical"}],"attributes":[{"id":"A409","pred":"chebi_id","subj":"T409","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A410","pred":"chebi_id","subj":"T410","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A411","pred":"chebi_id","subj":"T411","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A412","pred":"chebi_id","subj":"T412","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A413","pred":"chebi_id","subj":"T413","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A414","pred":"chebi_id","subj":"T414","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A415","pred":"chebi_id","subj":"T415","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A416","pred":"chebi_id","subj":"T416","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A417","pred":"chebi_id","subj":"T417","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A418","pred":"chebi_id","subj":"T418","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A419","pred":"chebi_id","subj":"T419","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A420","pred":"chebi_id","subj":"T420","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A421","pred":"chebi_id","subj":"T421","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A422","pred":"chebi_id","subj":"T422","obj":"http://purl.obolibrary.org/obo/CHEBI_25106"},{"id":"A423","pred":"chebi_id","subj":"T423","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A424","pred":"chebi_id","subj":"T424","obj":"http://purl.obolibrary.org/obo/CHEBI_33232"},{"id":"A425","pred":"chebi_id","subj":"T425","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A426","pred":"chebi_id","subj":"T426","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-MedDRA","denotations":[{"id":"T22","span":{"begin":1110,"end":1117},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"},{"id":"T23","span":{"begin":2525,"end":2537},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"}],"attributes":[{"id":"A22","pred":"meddra_id","subj":"T22","obj":"http://purl.bioontology.org/ontology/MEDDRA/10061447"},{"id":"A23","pred":"meddra_id","subj":"T23","obj":"http://purl.bioontology.org/ontology/MEDDRA/10062026"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-CHEBI","denotations":[{"id":"T240","span":{"begin":157,"end":159},"obj":"Chemical"},{"id":"T241","span":{"begin":310,"end":312},"obj":"Chemical"},{"id":"T242","span":{"begin":599,"end":601},"obj":"Chemical"},{"id":"T243","span":{"begin":781,"end":783},"obj":"Chemical"},{"id":"T244","span":{"begin":857,"end":859},"obj":"Chemical"},{"id":"T245","span":{"begin":1069,"end":1071},"obj":"Chemical"},{"id":"T246","span":{"begin":1189,"end":1191},"obj":"Chemical"},{"id":"T247","span":{"begin":1466,"end":1468},"obj":"Chemical"},{"id":"T248","span":{"begin":2196,"end":2198},"obj":"Chemical"},{"id":"T249","span":{"begin":2294,"end":2296},"obj":"Chemical"},{"id":"T250","span":{"begin":2419,"end":2421},"obj":"Chemical"},{"id":"T251","span":{"begin":2595,"end":2607},"obj":"Chemical"},{"id":"T252","span":{"begin":2730,"end":2732},"obj":"Chemical"},{"id":"T253","span":{"begin":2768,"end":2777},"obj":"Chemical"},{"id":"T254","span":{"begin":2968,"end":2970},"obj":"Chemical"},{"id":"T255","span":{"begin":3063,"end":3065},"obj":"Chemical"}],"attributes":[{"id":"A253","pred":"chebi_id","subj":"T253","obj":"http://purl.obolibrary.org/obo/CHEBI_25106"},{"id":"A255","pred":"chebi_id","subj":"T255","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A254","pred":"chebi_id","subj":"T254","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A242","pred":"chebi_id","subj":"T242","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A245","pred":"chebi_id","subj":"T245","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A252","pred":"chebi_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A240","pred":"chebi_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A243","pred":"chebi_id","subj":"T243","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A241","pred":"chebi_id","subj":"T241","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A250","pred":"chebi_id","subj":"T250","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A246","pred":"chebi_id","subj":"T246","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A244","pred":"chebi_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A251","pred":"chebi_id","subj":"T251","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A248","pred":"chebi_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A249","pred":"chebi_id","subj":"T249","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A247","pred":"chebi_id","subj":"T247","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T139","span":{"begin":16,"end":24},"obj":"Species"},{"id":"T140","span":{"begin":244,"end":254},"obj":"Species"},{"id":"T141","span":{"begin":541,"end":549},"obj":"Species"},{"id":"T142","span":{"begin":657,"end":665},"obj":"Species"},{"id":"T143","span":{"begin":675,"end":683},"obj":"Species"},{"id":"T144","span":{"begin":693,"end":703},"obj":"Species"},{"id":"T145","span":{"begin":796,"end":806},"obj":"Species"},{"id":"T146","span":{"begin":903,"end":911},"obj":"Species"},{"id":"T147","span":{"begin":1081,"end":1092},"obj":"Species"},{"id":"T148","span":{"begin":1229,"end":1246},"obj":"Species"},{"id":"T149","span":{"begin":1443,"end":1451},"obj":"Species"},{"id":"T150","span":{"begin":1489,"end":1497},"obj":"Species"},{"id":"T151","span":{"begin":1867,"end":1875},"obj":"Species"},{"id":"T152","span":{"begin":2143,"end":2151},"obj":"Species"},{"id":"T153","span":{"begin":2269,"end":2275},"obj":"Species"},{"id":"T154","span":{"begin":2314,"end":2323},"obj":"Species"},{"id":"T155","span":{"begin":2395,"end":2401},"obj":"Species"},{"id":"T156","span":{"begin":2457,"end":2467},"obj":"Species"},{"id":"T157","span":{"begin":2857,"end":2865},"obj":"Species"},{"id":"T158","span":{"begin":2992,"end":3000},"obj":"Species"},{"id":"T159","span":{"begin":3116,"end":3124},"obj":"Species"}],"attributes":[{"id":"A149","pred":"ncbi_taxonomy_id","subj":"T149","obj":"NCBItxid:2697049"},{"id":"A140","pred":"ncbi_taxonomy_id","subj":"T140","obj":"NCBItxid:2697049"},{"id":"A150","pred":"ncbi_taxonomy_id","subj":"T150","obj":"NCBItxid:2697049"},{"id":"A153","pred":"ncbi_taxonomy_id","subj":"T153","obj":"NCBItxid:9989"},{"id":"A154","pred":"ncbi_taxonomy_id","subj":"T154","obj":"NCBItxid:31631"},{"id":"A145","pred":"ncbi_taxonomy_id","subj":"T145","obj":"NCBItxid:2697049"},{"id":"A144","pred":"ncbi_taxonomy_id","subj":"T144","obj":"NCBItxid:2697049"},{"id":"A146","pred":"ncbi_taxonomy_id","subj":"T146","obj":"NCBItxid:2697049"},{"id":"A147","pred":"ncbi_taxonomy_id","subj":"T147","obj":"NCBItxid:1570291"},{"id":"A143","pred":"ncbi_taxonomy_id","subj":"T143","obj":"NCBItxid:1335626"},{"id":"A157","pred":"ncbi_taxonomy_id","subj":"T157","obj":"NCBItxid:2697049"},{"id":"A156","pred":"ncbi_taxonomy_id","subj":"T156","obj":"NCBItxid:2697049"},{"id":"A152","pred":"ncbi_taxonomy_id","subj":"T152","obj":"NCBItxid:2697049"},{"id":"A158","pred":"ncbi_taxonomy_id","subj":"T158","obj":"NCBItxid:2697049"},{"id":"A148","pred":"ncbi_taxonomy_id","subj":"T148","obj":"NCBItxid:37124"},{"id":"A155","pred":"ncbi_taxonomy_id","subj":"T155","obj":"NCBItxid:9605"},{"id":"A159","pred":"ncbi_taxonomy_id","subj":"T159","obj":"NCBItxid:2697049"},{"id":"A141","pred":"ncbi_taxonomy_id","subj":"T141","obj":"NCBItxid:2697049"},{"id":"A139","pred":"ncbi_taxonomy_id","subj":"T139","obj":"NCBItxid:2697049"},{"id":"A151","pred":"ncbi_taxonomy_id","subj":"T151","obj":"NCBItxid:2697049"},{"id":"A142","pred":"ncbi_taxonomy_id","subj":"T142","obj":"NCBItxid:694009"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T267","span":{"begin":0,"end":58},"obj":"Sentence"},{"id":"T268","span":{"begin":59,"end":156},"obj":"Sentence"},{"id":"T269","span":{"begin":157,"end":283},"obj":"Sentence"},{"id":"T270","span":{"begin":284,"end":463},"obj":"Sentence"},{"id":"T271","span":{"begin":464,"end":550},"obj":"Sentence"},{"id":"T272","span":{"begin":551,"end":712},"obj":"Sentence"},{"id":"T273","span":{"begin":713,"end":815},"obj":"Sentence"},{"id":"T274","span":{"begin":816,"end":1030},"obj":"Sentence"},{"id":"T275","span":{"begin":1031,"end":1175},"obj":"Sentence"},{"id":"T276","span":{"begin":1176,"end":1340},"obj":"Sentence"},{"id":"T277","span":{"begin":1341,"end":1586},"obj":"Sentence"},{"id":"T278","span":{"begin":1587,"end":1674},"obj":"Sentence"},{"id":"T279","span":{"begin":1675,"end":1836},"obj":"Sentence"},{"id":"T280","span":{"begin":1837,"end":2173},"obj":"Sentence"},{"id":"T281","span":{"begin":2174,"end":2266},"obj":"Sentence"},{"id":"T282","span":{"begin":2267,"end":2382},"obj":"Sentence"},{"id":"T283","span":{"begin":2383,"end":2538},"obj":"Sentence"},{"id":"T284","span":{"begin":2539,"end":2716},"obj":"Sentence"},{"id":"T285","span":{"begin":2717,"end":2887},"obj":"Sentence"},{"id":"T286","span":{"begin":2888,"end":3231},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T21","span":{"begin":2372,"end":2376},"obj":"Body_part"}],"attributes":[{"id":"A21","pred":"uberon_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/UBERON_0001913"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

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present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T147","span":{"begin":891,"end":899},"obj":"http://purl.obolibrary.org/obo/OGMS_0000020"},{"id":"T148","span":{"begin":972,"end":979},"obj":"http://purl.obolibrary.org/obo/OGMS_0000031"},{"id":"T149","span":{"begin":1087,"end":1092},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T150","span":{"begin":1105,"end":1109},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T151","span":{"begin":1241,"end":1246},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T152","span":{"begin":1296,"end":1305},"obj":"http://purl.obolibrary.org/obo/IDO_0000586"},{"id":"T153","span":{"begin":2233,"end":2240},"obj":"http://purl.obolibrary.org/obo/OGMS_0000031"},{"id":"T154","span":{"begin":2468,"end":2477},"obj":"http://purl.obolibrary.org/obo/IDO_0000586"},{"id":"T155","span":{"begin":2626,"end":2631},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T127","span":{"begin":367,"end":375},"obj":"Body_part"},{"id":"T128","span":{"begin":1105,"end":1109},"obj":"Body_part"},{"id":"T129","span":{"begin":2372,"end":2376},"obj":"Body_part"}],"attributes":[{"id":"A129","pred":"fma_id","subj":"T129","obj":"http://purl.org/sig/ont/fma/fma62100"},{"id":"A128","pred":"fma_id","subj":"T128","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A127","pred":"fma_id","subj":"T127","obj":"http://purl.org/sig/ont/fma/fma67180"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T77","span":{"begin":376,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0045851"},{"id":"T78","span":{"begin":408,"end":423},"obj":"http://purl.obolibrary.org/obo/GO_0061025"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T151","span":{"begin":16,"end":24},"obj":"Disease"},{"id":"T152","span":{"begin":244,"end":254},"obj":"Disease"},{"id":"T153","span":{"begin":541,"end":549},"obj":"Disease"},{"id":"T154","span":{"begin":657,"end":665},"obj":"Disease"},{"id":"T155","span":{"begin":693,"end":703},"obj":"Disease"},{"id":"T156","span":{"begin":796,"end":806},"obj":"Disease"},{"id":"T157","span":{"begin":903,"end":911},"obj":"Disease"},{"id":"T158","span":{"begin":1081,"end":1086},"obj":"Disease"},{"id":"T159","span":{"begin":1229,"end":1240},"obj":"Disease"},{"id":"T160","span":{"begin":1296,"end":1305},"obj":"Disease"},{"id":"T161","span":{"begin":1443,"end":1451},"obj":"Disease"},{"id":"T162","span":{"begin":1489,"end":1497},"obj":"Disease"},{"id":"T163","span":{"begin":1867,"end":1875},"obj":"Disease"},{"id":"T164","span":{"begin":2143,"end":2151},"obj":"Disease"},{"id":"T165","span":{"begin":2457,"end":2467},"obj":"Disease"},{"id":"T166","span":{"begin":2468,"end":2477},"obj":"Disease"},{"id":"T167","span":{"begin":2857,"end":2865},"obj":"Disease"},{"id":"T168","span":{"begin":2992,"end":3000},"obj":"Disease"},{"id":"T169","span":{"begin":3116,"end":3124},"obj":"Disease"}],"attributes":[{"id":"A160","pred":"mondo_id","subj":"T160","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A154","pred":"mondo_id","subj":"T154","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A159","pred":"mondo_id","subj":"T159","obj":"http://purl.obolibrary.org/obo/MONDO_0017941"},{"id":"A153","pred":"mondo_id","subj":"T153","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A157","pred":"mondo_id","subj":"T157","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A163","pred":"mondo_id","subj":"T163","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A169","pred":"mondo_id","subj":"T169","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A165","pred":"mondo_id","subj":"T165","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A152","pred":"mondo_id","subj":"T152","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A158","pred":"mondo_id","subj":"T158","obj":"http://purl.obolibrary.org/obo/MONDO_0005737"},{"id":"A151","pred":"mondo_id","subj":"T151","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A162","pred":"mondo_id","subj":"T162","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A161","pred":"mondo_id","subj":"T161","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A155","pred":"mondo_id","subj":"T155","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A156","pred":"mondo_id","subj":"T156","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A164","pred":"mondo_id","subj":"T164","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A166","pred":"mondo_id","subj":"T166","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A167","pred":"mondo_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A168","pred":"mondo_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T68","span":{"begin":376,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0045851"},{"id":"T69","span":{"begin":408,"end":423},"obj":"http://purl.obolibrary.org/obo/GO_0061025"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T64","span":{"begin":376,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0045851"},{"id":"T65","span":{"begin":408,"end":423},"obj":"http://purl.obolibrary.org/obo/GO_0061025"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

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present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"LitCovid-sentences","denotations":[{"id":"T267","span":{"begin":0,"end":58},"obj":"Sentence"},{"id":"T268","span":{"begin":59,"end":156},"obj":"Sentence"},{"id":"T269","span":{"begin":157,"end":283},"obj":"Sentence"},{"id":"T270","span":{"begin":284,"end":463},"obj":"Sentence"},{"id":"T271","span":{"begin":464,"end":550},"obj":"Sentence"},{"id":"T272","span":{"begin":551,"end":712},"obj":"Sentence"},{"id":"T273","span":{"begin":713,"end":815},"obj":"Sentence"},{"id":"T274","span":{"begin":816,"end":1030},"obj":"Sentence"},{"id":"T275","span":{"begin":1031,"end":1175},"obj":"Sentence"},{"id":"T276","span":{"begin":1176,"end":1340},"obj":"Sentence"},{"id":"T277","span":{"begin":1341,"end":1586},"obj":"Sentence"},{"id":"T278","span":{"begin":1587,"end":1674},"obj":"Sentence"},{"id":"T279","span":{"begin":1675,"end":1836},"obj":"Sentence"},{"id":"T280","span":{"begin":1837,"end":2173},"obj":"Sentence"},{"id":"T281","span":{"begin":2174,"end":2266},"obj":"Sentence"},{"id":"T282","span":{"begin":2267,"end":2382},"obj":"Sentence"},{"id":"T283","span":{"begin":2383,"end":2538},"obj":"Sentence"},{"id":"T284","span":{"begin":2539,"end":2716},"obj":"Sentence"},{"id":"T285","span":{"begin":2717,"end":2887},"obj":"Sentence"},{"id":"T286","span":{"begin":2888,"end":3231},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}

{"project":"2_test","denotations":[{"id":"32496926-15351731-132195715","span":{"begin":667,"end":669},"obj":"15351731"},{"id":"32496926-16115318-132195716","span":{"begin":670,"end":672},"obj":"16115318"},{"id":"32496926-24841269-132195717","span":{"begin":685,"end":687},"obj":"24841269"},{"id":"32496926-32020029-132195718","span":{"begin":705,"end":707},"obj":"32020029"},{"id":"32496926-32194981-132195718","span":{"begin":705,"end":707},"obj":"32194981"},{"id":"32496926-32194981-132195719","span":{"begin":808,"end":810},"obj":"32194981"},{"id":"32496926-23577127-132195720","span":{"begin":1168,"end":1170},"obj":"23577127"},{"id":"32496926-26459826-132195721","span":{"begin":1171,"end":1173},"obj":"26459826"},{"id":"32496926-19506054-132195722","span":{"begin":2378,"end":2380},"obj":"19506054"}],"text":"At present, the COVID-19 pandemic is continuing worldwide. It is still an urgent need to find effective therapies and vaccines for treatment and prevention. CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. In addition, the optimal daily dose and duration of treatment course are not yet clear. One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies."}