PMC:7441788 / 28509-34097 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T117","span":{"begin":1423,"end":1434},"obj":"Body_part"}],"attributes":[{"id":"A117","pred":"fma_id","subj":"T117","obj":"http://purl.org/sig/ont/fma/fma54878"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T14","span":{"begin":1423,"end":1434},"obj":"Body_part"}],"attributes":[{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0001728"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T124","span":{"begin":127,"end":135},"obj":"Disease"},{"id":"T125","span":{"begin":1102,"end":1110},"obj":"Disease"},{"id":"T126","span":{"begin":2454,"end":2462},"obj":"Disease"},{"id":"T127","span":{"begin":2885,"end":2893},"obj":"Disease"},{"id":"T128","span":{"begin":3989,"end":3997},"obj":"Disease"},{"id":"T129","span":{"begin":4783,"end":4793},"obj":"Disease"},{"id":"T130","span":{"begin":5000,"end":5011},"obj":"Disease"},{"id":"T131","span":{"begin":5551,"end":5561},"obj":"Disease"}],"attributes":[{"id":"A124","pred":"mondo_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A125","pred":"mondo_id","subj":"T125","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A126","pred":"mondo_id","subj":"T126","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A127","pred":"mondo_id","subj":"T127","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A128","pred":"mondo_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A129","pred":"mondo_id","subj":"T129","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"},{"id":"A130","pred":"mondo_id","subj":"T130","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"},{"id":"A131","pred":"mondo_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T218","span":{"begin":95,"end":96},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T219","span":{"begin":216,"end":218},"obj":"http://purl.obolibrary.org/obo/CLO_0001313"},{"id":"T220","span":{"begin":477,"end":482},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T221","span":{"begin":486,"end":489},"obj":"http://purl.obolibrary.org/obo/CLO_0001000"},{"id":"T222","span":{"begin":532,"end":537},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T223","span":{"begin":757,"end":758},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T224","span":{"begin":1052,"end":1053},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T225","span":{"begin":1629,"end":1634},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T226","span":{"begin":1884,"end":1885},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T227","span":{"begin":2233,"end":2234},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T228","span":{"begin":2822,"end":2823},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T229","span":{"begin":2866,"end":2867},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T230","span":{"begin":3834,"end":3835},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T231","span":{"begin":4017,"end":4018},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T232","span":{"begin":4123,"end":4124},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T233","span":{"begin":4181,"end":4182},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T234","span":{"begin":4385,"end":4386},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T235","span":{"begin":4453,"end":4454},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T236","span":{"begin":4644,"end":4645},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T237","span":{"begin":4700,"end":4701},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T238","span":{"begin":4760,"end":4761},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T239","span":{"begin":4888,"end":4889},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T240","span":{"begin":5033,"end":5034},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T241","span":{"begin":5075,"end":5076},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T242","span":{"begin":5220,"end":5227},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T243","span":{"begin":5442,"end":5445},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T244","span":{"begin":5474,"end":5475},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

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"pred":"chebi_id","subj":"T347","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A316","pred":"chebi_id","subj":"T316","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A358","pred":"chebi_id","subj":"T358","obj":"http://purl.obolibrary.org/obo/CHEBI_25106"},{"id":"A345","pred":"chebi_id","subj":"T345","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A356","pred":"chebi_id","subj":"T356","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A319","pred":"chebi_id","subj":"T319","obj":"http://purl.obolibrary.org/obo/CHEBI_2955"},{"id":"A342","pred":"chebi_id","subj":"T342","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A323","pred":"chebi_id","subj":"T323","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A299","pred":"chebi_id","subj":"T299","obj":"http://purl.obolibrary.org/obo/CHEBI_33232"},{"id":"A331","pred":"chebi_id","subj":"T331","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-MedDRA","denotations":[{"id":"T16","span":{"begin":36,"end":48},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"},{"id":"T17","span":{"begin":1029,"end":1039},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"},{"id":"T18","span":{"begin":1435,"end":1445},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"},{"id":"T19","span":{"begin":1635,"end":1642},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"}],"attributes":[{"id":"A16","pred":"meddra_id","subj":"T16","obj":"http://purl.bioontology.org/ontology/MEDDRA/10062026"},{"id":"A19","pred":"meddra_id","subj":"T19","obj":"http://purl.bioontology.org/ontology/MEDDRA/10061447"},{"id":"A17","pred":"meddra_id","subj":"T17","obj":"http://purl.bioontology.org/ontology/MEDDRA/10062178"},{"id":"A18","pred":"meddra_id","subj":"T18","obj":"http://purl.bioontology.org/ontology/MEDDRA/10062178"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

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are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T122","span":{"begin":127,"end":135},"obj":"Species"},{"id":"T123","span":{"begin":1102,"end":1110},"obj":"Species"},{"id":"T124","span":{"begin":2454,"end":2462},"obj":"Species"},{"id":"T125","span":{"begin":2885,"end":2893},"obj":"Species"},{"id":"T126","span":{"begin":3989,"end":3997},"obj":"Species"},{"id":"T127","span":{"begin":5220,"end":5227},"obj":"Species"}],"attributes":[{"id":"A125","pred":"ncbi_taxonomy_id","subj":"T125","obj":"NCBItxid:2697049"},{"id":"A124","pred":"ncbi_taxonomy_id","subj":"T124","obj":"NCBItxid:2697049"},{"id":"A123","pred":"ncbi_taxonomy_id","subj":"T123","obj":"NCBItxid:2697049"},{"id":"A126","pred":"ncbi_taxonomy_id","subj":"T126","obj":"NCBItxid:2697049"},{"id":"A122","pred":"ncbi_taxonomy_id","subj":"T122","obj":"NCBItxid:2697049"},{"id":"A127","pred":"ncbi_taxonomy_id","subj":"T127","obj":"NCBItxid:10239"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T201","span":{"begin":0,"end":146},"obj":"Sentence"},{"id":"T202","span":{"begin":147,"end":330},"obj":"Sentence"},{"id":"T203","span":{"begin":331,"end":495},"obj":"Sentence"},{"id":"T204","span":{"begin":496,"end":665},"obj":"Sentence"},{"id":"T205","span":{"begin":666,"end":778},"obj":"Sentence"},{"id":"T206","span":{"begin":779,"end":988},"obj":"Sentence"},{"id":"T207","span":{"begin":989,"end":1072},"obj":"Sentence"},{"id":"T208","span":{"begin":1073,"end":1418},"obj":"Sentence"},{"id":"T209","span":{"begin":1419,"end":1591},"obj":"Sentence"},{"id":"T210","span":{"begin":1592,"end":1685},"obj":"Sentence"},{"id":"T211","span":{"begin":1686,"end":1778},"obj":"Sentence"},{"id":"T212","span":{"begin":1779,"end":1883},"obj":"Sentence"},{"id":"T213","span":{"begin":1884,"end":2160},"obj":"Sentence"},{"id":"T214","span":{"begin":2161,"end":2292},"obj":"Sentence"},{"id":"T215","span":{"begin":2293,"end":2463},"obj":"Sentence"},{"id":"T216","span":{"begin":2464,"end":2578},"obj":"Sentence"},{"id":"T217","span":{"begin":2579,"end":2706},"obj":"Sentence"},{"id":"T218","span":{"begin":2707,"end":2818},"obj":"Sentence"},{"id":"T219","span":{"begin":2819,"end":3106},"obj":"Sentence"},{"id":"T220","span":{"begin":3107,"end":3286},"obj":"Sentence"},{"id":"T221","span":{"begin":3287,"end":3517},"obj":"Sentence"},{"id":"T222","span":{"begin":3518,"end":3632},"obj":"Sentence"},{"id":"T223","span":{"begin":3633,"end":3823},"obj":"Sentence"},{"id":"T224","span":{"begin":3824,"end":4016},"obj":"Sentence"},{"id":"T225","span":{"begin":4017,"end":4072},"obj":"Sentence"},{"id":"T226","span":{"begin":4073,"end":4228},"obj":"Sentence"},{"id":"T227","span":{"begin":4229,"end":4561},"obj":"Sentence"},{"id":"T228","span":{"begin":4562,"end":4822},"obj":"Sentence"},{"id":"T229","span":{"begin":4823,"end":5012},"obj":"Sentence"},{"id":"T230","span":{"begin":5013,"end":5103},"obj":"Sentence"},{"id":"T231","span":{"begin":5104,"end":5321},"obj":"Sentence"},{"id":"T232","span":{"begin":5322,"end":5588},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T12","span":{"begin":1423,"end":1434},"obj":"Body_part"}],"attributes":[{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0001728"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

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are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T134","span":{"begin":477,"end":482},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T135","span":{"begin":532,"end":537},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T136","span":{"begin":1314,"end":1322},"obj":"http://purl.obolibrary.org/obo/OGMS_0000020"},{"id":"T137","span":{"begin":1629,"end":1634},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T138","span":{"begin":4286,"end":4293},"obj":"http://purl.obolibrary.org/obo/OGMS_0000031"},{"id":"T139","span":{"begin":5220,"end":5227},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T116","span":{"begin":1423,"end":1434},"obj":"Body_part"}],"attributes":[{"id":"A116","pred":"fma_id","subj":"T116","obj":"http://purl.org/sig/ont/fma/fma54878"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-MAT","denotations":[{"id":"T8","span":{"begin":1423,"end":1434},"obj":"http://purl.obolibrary.org/obo/MAT_0000447"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T74","span":{"begin":2250,"end":2255},"obj":"http://purl.obolibrary.org/obo/GO_0016265"},{"id":"T75","span":{"begin":4957,"end":4962},"obj":"http://purl.obolibrary.org/obo/GO_0016265"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T117","span":{"begin":127,"end":135},"obj":"Disease"},{"id":"T118","span":{"begin":1102,"end":1110},"obj":"Disease"},{"id":"T119","span":{"begin":2454,"end":2462},"obj":"Disease"},{"id":"T120","span":{"begin":2885,"end":2893},"obj":"Disease"},{"id":"T121","span":{"begin":3989,"end":3997},"obj":"Disease"},{"id":"T122","span":{"begin":4783,"end":4793},"obj":"Disease"},{"id":"T123","span":{"begin":5000,"end":5011},"obj":"Disease"},{"id":"T124","span":{"begin":5551,"end":5561},"obj":"Disease"}],"attributes":[{"id":"A117","pred":"mondo_id","subj":"T117","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A120","pred":"mondo_id","subj":"T120","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A124","pred":"mondo_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"},{"id":"A122","pred":"mondo_id","subj":"T122","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"},{"id":"A123","pred":"mondo_id","subj":"T123","obj":"http://purl.obolibrary.org/obo/MONDO_0007263"},{"id":"A119","pred":"mondo_id","subj":"T119","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A121","pred":"mondo_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A118","pred":"mondo_id","subj":"T118","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sample-PD-HP","denotations":[{"id":"T21","span":{"begin":4771,"end":4793},"obj":"Phenotype"},{"id":"T22","span":{"begin":4988,"end":5011},"obj":"Phenotype"},{"id":"T23","span":{"begin":5551,"end":5561},"obj":"Phenotype"}],"attributes":[{"id":"A21","pred":"hp_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/HP_0004308"},{"id":"A23","pred":"hp_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/HP_0011675"},{"id":"A22","pred":"hp_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/HP_0004308"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

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are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-sentences","denotations":[{"id":"T201","span":{"begin":0,"end":146},"obj":"Sentence"},{"id":"T202","span":{"begin":147,"end":330},"obj":"Sentence"},{"id":"T203","span":{"begin":331,"end":495},"obj":"Sentence"},{"id":"T204","span":{"begin":496,"end":665},"obj":"Sentence"},{"id":"T205","span":{"begin":666,"end":778},"obj":"Sentence"},{"id":"T206","span":{"begin":779,"end":988},"obj":"Sentence"},{"id":"T207","span":{"begin":989,"end":1072},"obj":"Sentence"},{"id":"T208","span":{"begin":1073,"end":1418},"obj":"Sentence"},{"id":"T209","span":{"begin":1419,"end":1591},"obj":"Sentence"},{"id":"T210","span":{"begin":1592,"end":1685},"obj":"Sentence"},{"id":"T211","span":{"begin":1686,"end":1778},"obj":"Sentence"},{"id":"T212","span":{"begin":1779,"end":1883},"obj":"Sentence"},{"id":"T213","span":{"begin":1884,"end":2160},"obj":"Sentence"},{"id":"T214","span":{"begin":2161,"end":2292},"obj":"Sentence"},{"id":"T215","span":{"begin":2293,"end":2463},"obj":"Sentence"},{"id":"T216","span":{"begin":2464,"end":2578},"obj":"Sentence"},{"id":"T217","span":{"begin":2579,"end":2706},"obj":"Sentence"},{"id":"T218","span":{"begin":2707,"end":2818},"obj":"Sentence"},{"id":"T219","span":{"begin":2819,"end":3106},"obj":"Sentence"},{"id":"T220","span":{"begin":3107,"end":3286},"obj":"Sentence"},{"id":"T221","span":{"begin":3287,"end":3517},"obj":"Sentence"},{"id":"T222","span":{"begin":3518,"end":3632},"obj":"Sentence"},{"id":"T223","span":{"begin":3633,"end":3823},"obj":"Sentence"},{"id":"T224","span":{"begin":3824,"end":4016},"obj":"Sentence"},{"id":"T225","span":{"begin":4017,"end":4072},"obj":"Sentence"},{"id":"T226","span":{"begin":4073,"end":4228},"obj":"Sentence"},{"id":"T227","span":{"begin":4229,"end":4561},"obj":"Sentence"},{"id":"T228","span":{"begin":4562,"end":4822},"obj":"Sentence"},{"id":"T229","span":{"begin":4823,"end":5012},"obj":"Sentence"},{"id":"T230","span":{"begin":5013,"end":5103},"obj":"Sentence"},{"id":"T231","span":{"begin":5104,"end":5321},"obj":"Sentence"},{"id":"T232","span":{"begin":5322,"end":5588},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T22","span":{"begin":4771,"end":4793},"obj":"Phenotype"},{"id":"T23","span":{"begin":4988,"end":5011},"obj":"Phenotype"},{"id":"T24","span":{"begin":5551,"end":5561},"obj":"Phenotype"}],"attributes":[{"id":"A22","pred":"hp_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/HP_0004308"},{"id":"A23","pred":"hp_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/HP_0004308"},{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0011675"}],"text":"There are also several reports that investigated the efficacy of CQ or HCQ in combination with a macrolide in the treatment of COVID-19 (Table 1). In an open nonrandom clinical trial conducted in France [57], of the 36 participants, 20 patients were given HCQ (200 mg/3 times) with 6 receiving added azithromycin, and 16 controls. The results showed that compared with the control group, HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days. On the 6th day after treatment, the virus clearance rates of HCQ combined with azithromycin, HCQ alone and controls were 100%, 57.1% and 12.5%, respectively (P \u003c 0.001). This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect. However, the trial design and the results were unreliable, as six patients in the HCQ group discontinued treatment early due to critical illness or intolerance to the drugs and were excluded from the analysis. The assessment of efficacy was based on viral load rather than a clinical endpoint. An observational study in 80 COVID-19 patients evaluated the efficacy of HCQ (200 mg/3 times/day for 10 days) in combination with azithromycin (500 mg on the first day, 250 mg/day afterward for 5 days) and showed that all patients’ clinical symptoms were improved, except for one patient aged over 86 years who died due to critical illness [58]. The nasopharynx viral load in most patients decreased rapidly, and the negative rates of viral nucleic acid conversion on days 7 and 8 were about 83% and 93%, respectively. About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day. However, this study had no control group, thus the results were difficult to interpret [58]. Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin. A retrospective study including 368 patients (97 patients received HCQ, 113 patients received HCQ + azithromycin and 158 patients received no HCQ) from USA [59] showed that the rates of ventilation in the HCQ, HCQ+azithromycin and no HCQ groups had no significant differences. Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group. This study showed no evidence that the use of HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19. Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59]. In this study, the subjects included were only men and most of them were black, which may affect the generality of the results. In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results. In a retrospective multicenter cohort study of a random sample of COVID-19 patients from 25 hospitals in New York [60], totaling 1438 patients, 735 received HCQ and azithromycin, 271 received HCQ alone, 211 received azithromycin alone and 221 received neither drug (HCQ or azithromycin). The results showed that the hospital mortality rate of patients receiving HCQ＋azithromycin was 25.7%, HCQ alone was 19.9%, azithromycin alone was 10.0% and neither drug was 12.7%. In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in hospital mortality rate for patients receiving HC＋azithromycin, HCQ alone, or azithromycin alone. In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization. However, the mortality rate of this study was limited to in-hospital deaths, and patients discharged during the study period were considered alive, which may underestimate the morality rate. Recently, a multinational registry analysis about HCQ or CQ with or without second-generation macrolides (especial azithromycin and clarithromycin) for treatment of COVID-19 was reported [61]. A total of 96,032 patients were included in this study. Of these, 1868 received CQ, 3783 received CQ with a macrolide, 3016 received HCQ and 6221 received HCQ with a macrolide and 8114 patients as control group. After controlling various confounding factors related to disease, when compared with the mortality in the control group (9.3%), CQ group was 16.4%, CQ with a macrolide group was 22.2%, HCQ group was 18.0% and HCQ group with a macrolide was 23.8%; each group was associated with an increased risk of hospital mortality independently. Apart from this, compared with the control group (0.3%), CQ group (4.3%), CQ with a macrolide group (6.5%), HCQ group (6.1%) and HCQ with a macrolide group (8.1%) were independently associated with a risk for ventricular arrhythmia during hospitalization [61]. This study showed that CQ or HCQ (used alone or combination with a macrolide) was associated with an increased hazard for in-hospital death and an increased risk of ventricular arrhythmias. This study included a large number of patients, but it is not a randomized clinical trial. In short, some small studies have shown that HCQ combined with azithromycin could quickly and effectively eliminate viruses, but the design of these studies was flawed in many aspects, making the results unconvincing. Several subsequent studies have shown that the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) has no obvious correlation with a reduced risk for mechanical ventilation, and may even increase the risk of arrhythmia and in-hospital mortality."}