LitCovid-sentences  

PMC:7441788 / 14475-35313 JSONTXT 25 Projects

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Id Subject Object Predicate Lexical cue
T104 0-2 Sentence denotes 5.
T105 4-60 Sentence denotes Clinical efficacy of CQ/HCQ in the treatment of COVID-19
T106 61-160 Sentence denotes Only two published clinical reports have studied the efficacy of CQ in COVID-19 patients (Table 1).
T107 161-414 Sentence denotes One study used CQ to treat more than 100 patients with COVID-19 and claimed that CQ was superior to the control group in suppressing the deterioration of pneumonia, improving lung imaging, promoting viral conversion and shortening the course of disease.
T108 415-480 Sentence denotes Serious adverse effects were not observed in these patients [48].
T109 481-617 Sentence denotes However, this report did not provide any details about the study design and patient data, thus it is difficult to evaluate the validity.
T110 618-720 Sentence denotes Recently, a parallel, double-blind, randomized, phase IIB clinical trial was performed in Brazil [49].
T111 721-802 Sentence denotes In this study, 81 severe COVID-19 patients were randomly divided into two groups:
T112 803-970 Sentence denotes 41 patients received high-dose CQ (600 mg/2 times/day for 10 day) and 40 patients received low-dose CQ (450 mg/2 times on day 1 and then 450 mg/1 time/day for 4 days).
T113 971-1082 Sentence denotes The 13-day mortality rate in the high-dose group was more than double that in low-dose group (39.0% vs. 16.0%).
T114 1083-1259 Sentence denotes The high-dosage group exhibited more instance of corrected QT (QTc) interval prolongation (>500 milliseconds (ms); 7 of 37 [18.9%]) than the low-dosage group (4 of 36 [11.1%]).
T115 1260-1382 Sentence denotes These findings suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 [49].
T116 1383-1391 Sentence denotes Table 1.
T117 1392-1501 Sentence denotes Outcomes and advantage/limitation of chloroquine (CQ)/hydroxychloroquine (HCQ) clinical studies for COVID-19.
T118 1502-1583 Sentence denotes Author (Reference) Study design Patients Treatment Outcomes Advantage Limitations
T119 1584-1599 Sentence denotes Gao et al [48].
T120 1600-1829 Sentence denotes Rough and simple description Not mentioned CQ (No specific dosage was mentioned) CQ was superior to control in suppressing pneumonia deterioration, improving lung imaging, promoting viral conversion and shortening disease course.
T121 1830-1846 Sentence denotes Not significant.
T122 1847-1973 Sentence denotes No study design and the specific number of patients and controls were provided and thus the result appears to be unconvincing.
T123 1974-1991 Sentence denotes Borba et al [49].
T124 1992-2478 Sentence denotes Randomized controlled trial High-dose CQ group: n = 40;Low-dose CQ group:n = 41 high-dose CQ (600 mg/2 times/day, for 10 day);low-dose CQ (450 mg/2 times/day for 5 days, double dose on 1st day) The mortality rate in the high-dose group was more than double that in low-dose group Double-blind study; 2 dosages of CQ for the first time in severe COVID-19 Small sample size; single-center design; Lack of a placebo control; Lack of exclusion criteria based on the QTc interval at baseline
T125 2479-2697 Sentence denotes Chen et al.[50] Randomized trial HCQ group: n = 31; control group: n = 30 HCQ (200 mg/2 times/day for 5 days) HCQ group have small improvement in body temperature and cough compered with control group Randomized trial.
T126 2698-2782 Sentence denotes Small sample size; Single-center design; Small improvement in temperature and cough.
T127 2783-2802 Sentence denotes Mahévas et al [53].
T128 2803-3021 Sentence denotes Comparative study HCQ group: n = 84; control group: n = 97 HCQ 600 mg/day for 7 days Compared with control group, a reduction of admissions to ICU or death 7 days after hospital admission was not observed in HCQ group.
T129 3022-3088 Sentence denotes Relatively larger sample size in HCQ treatment and control groups.
T130 3089-3199 Sentence denotes Nonrandomized design; In propensity score model, four possible important prognostic variables were unbalanced.
T131 3200-3216 Sentence denotes Tang et al [54].
T132 3217-3298 Sentence denotes Open label, randomized controlled trial HCQ group: n = 70; control group: n = 80.
T133 3299-3505 Sentence denotes HCQ 1200 mg daily for 3 days, 800 mg daily for 2 weeks (mild to moderate disease)/3 weeks(severe disease) HCQ did not show additional benefits of vial elimination in patients with mild to moderate COVID-19.
T134 3506-3534 Sentence denotes Randomized controlled study.
T135 3535-3733 Sentence denotes Lack of a placebo control group; Design introduces the possibility of biased investigator determined assessment and unbalanced dosage adjustment; Randomization of sequential envelopes may be biased.
T136 3734-3917 Sentence denotes The antiviral efficacy of HCQ was not assessed at an earlier stage; Most patients are mild to severe, and the effect of HCQ on disease progression or regression could not be provided.
T137 3918-3994 Sentence denotes The trial terminated early due to the difficulty to recruit enough patients.
T138 3995-4207 Sentence denotes Some secondary endpoints could not be analyzed by the cutoff date; Viral RNA specimens are mostly from the upper respiratory tract rather than bronchoalveolar lavage fluid, which may cause false negative results.
T139 4208-4227 Sentence denotes Geleris et al [55].
T140 4228-4471 Sentence denotes Observational study HCQ group: n = 811; no-HCQ group: n = 565 HCQ (600 mg/2 times on the first day, then 400 mg once a day for 4 days) No correlation between the HCQ use and significant higher or lower risk of intubation or death was observed.
T141 4472-4643 Sentence denotes Large sample size; Minimization of the unmeasured confusion and error through multivariable Cox model with inverse probability weighting according to the propensity score.
T142 4644-4753 Sentence denotes Single-center design; missing of some variables; Potential for inaccuracies in the electronic health records.
T143 4754-4768 Sentence denotes Yu et al [56].
T144 4769-4943 Sentence denotes Retrospective study HCQ group: n = 48; no-HCQ group: n = 502 HCQ (200 mg/2 times/day, for 7 to 10 days) The fatalities of HCQ group was significantly lower than no-HCQ group.
T145 4944-5072 Sentence denotes HCQ treatment was related to significantly reduced mortality in critically ill COVID-19 patients and greatly lowered IL-6 level.
T146 5073-5163 Sentence denotes Mortality was used as a measure of outcome and the study included critically ill patients.
T147 5164-5245 Sentence denotes Retrospective design of the study and the number of HCQ group patients was small.
T148 5246-5516 Sentence denotes Gautret et al.[57] Open label, nonrandom cohort study HCQ group: n = 12; HCQ＋azithromycin group: n = 6; control group: n = 12 HCQ (200 mg/3 times/day for 10 days) HCQ alone or in combination with azithromycin could effectively eliminate nasopharyngeal virus in 3–5 days.
T149 5517-5578 Sentence denotes Nasopharyngeal virus determination was used as main endpoint.
T150 5579-5728 Sentence denotes Small sample size; Six patients dropped out due to critical illness or intolerance to the drug; Lack of clinical outcomes; Limited follow-up results.
T151 5729-5748 Sentence denotes Gautret et al [58].
T152 5749-5992 Sentence denotes Observational study HCQ group: n = 80; no control HCQ, 200 mg/3 times/day for 10 days combined with azithromycin 500 mg on the 1st day, 250 mg/day afterward for 5 days The nasopharynx viral load in most patients received HCQ decreased rapidly.
T153 5993-6031 Sentence denotes Observation of nasopharynx viral load.
T154 6032-6116 Sentence denotes Observational study design and no control group; No clinical outcomes were analyzed.
T155 6117-6164 Sentence denotes Possible confounding factors were not adjusted.
T156 6165-6186 Sentence denotes Magagnoli et al [59].
T157 6187-6283 Sentence denotes Retrospective study HCQ group:n = 97HCQ＋azithromycin: n = 113No HCQ group:n = 158 Not specified.
T158 6284-6506 Sentence denotes The use of HCQ, either with or without azithromycin, didn’t reduce the risk of mechanical ventilation in patients hospitalized with COVID-19; Patients treated with HCQ alone was associated with increased overall mortality.
T159 6507-6728 Sentence denotes The study data comes from a comprehensive electronic medical record; Strictly defined covariates and outcomes; Using propensity scores adjustment for a large number of relevant confounders to make results more persuasive.
T160 6729-6922 Sentence denotes Retrospective nature of the study; The subjects included only men and most of them were black; Despite adjustments to many possible confounding factors, there may still be undiscovered factors.
T161 6923-7429 Sentence denotes Rosenberg et al[60] Retrospective multicenter cohort study HCQ group:n = 271;HCQ ＋azithromycin group:n = 735control group:n = 221 HCQ:200 mg/400 mg/600 mg/other/unknown, frequency: once a day/twice a day/other/unknownazithromycin:200 mg/250 mg/400 mg/500 mg/other/unknown, methods:Oral/IV/unknown,frequency: only once/once a day/twice a day/other/unknown Treatment with HCQ, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality.
T162 7430-7512 Sentence denotes This study include a large, random sample from 25 metropolitan New York hospitals.
T163 7513-7677 Sentence denotes The sample was drawnearly in the epidemic to include patients with long, complicated, and ongoing hospital stays; In-hospital mortality was used as primary outcome.
T164 7678-7819 Sentence denotes Retrospective study design; There may be missing information; Mortality was limited to in-hospital death; There may be potential confounders.
T165 7820-7899 Sentence denotes The dosing in the doses and frequencies of HCQ and azithromycin varied greatly.
T166 7900-7959 Sentence denotes The confidence intervals for some of the findings are wide.
T167 7960-8418 Sentence denotes Mehraet al[61] Multinational real-world analysis Teatment groups: n = 14,888Control group: n = 81,144 Mean daily dose: CQ 765 mg, (SD 308); HCQ 596 mg(126); CQ with a macrolide 790 mg(320); HCQ with a macrolide 597 mg(128).mean duration:CQ 6.6 days(2.4); HCQ 4.2 days(1.9);CQ with a macrolide 6.8 days(2.5); HCQ with a macrolide 4.3 days (2.0) A benefit of HCQ or CQ, when used alone or witha macrolide, on in-hospital outcomes for COVID-19 was not observed.
T168 8419-8493 Sentence denotes Large multinational real-world data and large number of study populations.
T169 8494-8812 Sentence denotes There may be potential confounders; It did not measure QT intervals and stratify the arrhythmia pattern; It did not determine whether the increased risk of death in-hospital and use of drug treatment regimens were directly related to cardiovascular risk; It did not observe the risk of the drug dose-response analysis.
T170 8813-8898 Sentence denotes Several trials evaluated the efficacy of HCQ for the treatment of COVID-19 (Table 1).
T171 8899-9051 Sentence denotes In a randomized clinical trial from Wuhan about HCQ treatment of mild COVID-19 [50], 31 out of 62 patients received HCQ (200 mg/2 times/day for 5 days).
T172 9052-9407 Sentence denotes The results showed that the temperature recovery time in the HCQ group was improved compared with the control group (average days, 2.2 vs. 3.2); the cough relief time was shorter in the HCQ group than the control group (average days, 2.4 vs. 3.1); and the improvement rate of pneumonia in the HCQ group was higher than the control group (80.6% vs. 54.8%).
T173 9408-9570 Sentence denotes However, only 48% of patients (15/31) in HCQ group and 71% of patients (22/31) in control group had cough at baseline and the duration of cough was not described.
T174 9571-9647 Sentence denotes Improvement of symptoms were small and the trial was terminated prematurely.
T175 9648-9742 Sentence denotes These factors and the low sample size compromise the reliability of the results of this study.
T176 9743-9949 Sentence denotes Importantly, evaluation of HCQ in the COVID-19 pandemic areas have shown that HCQ can help patients with mild symptoms, and may potentially reduce transmission in areas lacking isolation facilities [51,52].
T177 9950-10134 Sentence denotes However, in areas with strict isolation standards, the use of HCQ to reduce transmission or for treatment of mild COVID-19 cases may not be beneficial in risk-benefit analysis [51,52].
T178 10135-10260 Sentence denotes Nevertheless, there is an urgent need for drugs and therapeutics in severe cases, which require randomized controlled trials.
T179 10261-10387 Sentence denotes A study from four French tertiary care centers included 181 patients hospitalized for COVID-19 and requiring oxygen (2 L/min):
T180 10388-10502 Sentence denotes 84 patients received HCQ (600 mg/day) within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group) [53].
T181 10503-10688 Sentence denotes The results showed that the patients transferred to the ICU or died within 7 days and developed ARDS within 7 days had no significant differences between the HCQ group and no-HCQ group.
T182 10689-10782 Sentence denotes Eight patients in the HCQ group (9.5%) discontinued HCQ due to electrocardiogram alterations.
T183 10783-10897 Sentence denotes These results do not support the use of HCQ for treating hospitalized COVID-19-related hypoxic pneumonia patients.
T184 10898-11105 Sentence denotes It is worth noting that in the study’s propensity score model, four possible important prognostic variables were unbalanced and a center effect was not considered, which all can cause bias for study results.
T185 11106-11400 Sentence denotes In a multicenter, randomized, parallel trial about HCQ in patients with mainly mild to moderate COVID-19 [54], 80 patients received ‘standard care’ and 70 patients received HCQ (1200 mg daily for 3 days, and then 800 mg daily for 2 weeks [mild to moderate disease] or 3 weeks [severe disease]).
T186 11401-11554 Sentence denotes The results showed that the 28-days negative conversion probability in ‘standard care’＋HCQ group was 85.4%, similar to the ‘standard care’ group (81.2%).
T187 11555-11656 Sentence denotes HCQ did not show additional benefits of viral elimination in patients with mild to moderate COVID-19.
T188 11657-11801 Sentence denotes However, the study could not evaluate the antiviral effect of HCQ at early stages of disease, which is a critical period of antiviral treatment.
T189 11802-11961 Sentence denotes In addition, viral RNA specimens were mostly from the upper respiratory tract rather than bronchoalveolar lavage fluid, which may cause false negative results.
T190 11962-12113 Sentence denotes Due to the small number of severe patients, this study could not provide evidence regarding the effect of HCQ on the disease progression or regression.
T191 12114-12350 Sentence denotes In another large observational study involving 1376 cases of COVID-19 from New York, 811 patients received HCQ (600 mg/2 times on the first day, then 400 mg once a day for 4 days) within 24 or 48 hours of admission and 565 did not [55].
T192 12351-12461 Sentence denotes This study found no correlation between HCQ use and significantly higher or lower risk of intubation or death.
T193 12462-12637 Sentence denotes However, in this study, even after the propensity score-matching, the diseases in patients receiving HCQ were more severe at baseline than those in the patients not receiving.
T194 12638-12787 Sentence denotes Notably, according to another recent study [56], low dose of HCQ reduced fatality of critically ill patients with COVID-19 without apparent toxicity.
T195 12788-12957 Sentence denotes This retrospective study included 550 patients who need mechanical ventilation, of which 48 received HCQ treatment (200 mg/2 times/day for 7 to 10 days) and 502 did not.
T196 12958-13248 Sentence denotes The fatalities of the HCQ group was significantly lower than no-HCQ group (18.8% vs 47.4%, P < 0.05), and the inflammatory cytokine IL-6 in the HCQ group decreased significantly from 22.2 (8.3 to 118.9 pg/mL) at the beginning of treatment to 5.2 (3.0 to 23.4 pg/mL) at the end of treatment.
T197 13249-13440 Sentence denotes The authors deemed that the anti-inflammatory effect of low-dose HCQ and the activity of inhibiting viral replication may have important significance in critically ill patients with COVID-19.
T198 13441-13553 Sentence denotes Yet, this study is flawed due to its retrospective nature and the small number of HCQ treated patients included.
T199 13554-13818 Sentence denotes In short, some initial studies have shown that HCQ appears to have a curative effect on patients with mild COVID-19, but subsequent studies indicate that HCQ had no significant benefit in COVID-19 patients with viral conversion and the risk of intubation or death.
T200 13819-14033 Sentence denotes Although some recent studies show that low-dose HCQ could potentially reduce the mortality of severe COVID-19 patients, there are other studies showing that the HCQ use had no effect on risk of intubation or death.
T201 14034-14180 Sentence denotes 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).
T202 14181-14364 Sentence denotes 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.
T203 14365-14529 Sentence denotes 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.
T204 14530-14699 Sentence denotes 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 < 0.001).
T205 14700-14812 Sentence denotes This study indicated that the combined application of azithromycin and HCQ appears to have a synergistic effect.
T206 14813-15022 Sentence denotes 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.
T207 15023-15106 Sentence denotes The assessment of efficacy was based on viral load rather than a clinical endpoint.
T208 15107-15452 Sentence denotes 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].
T209 15453-15625 Sentence denotes 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.
T210 15626-15719 Sentence denotes About 97.5% of patients had negative virus culture in respiratory specimens on the fifth day.
T211 15720-15812 Sentence denotes However, this study had no control group, thus the results were difficult to interpret [58].
T212 15813-15917 Sentence denotes Some recent studies have yielded different results about the efficacy of HCQ combined with azithromycin.
T213 15918-16194 Sentence denotes 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.
T214 16195-16326 Sentence denotes Unfortunately, theHCQ group (but not in the HCQ+azithromycin group) had a higher risk of death from any case than the no HCQ group.
T215 16327-16497 Sentence denotes 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.
T216 16498-16612 Sentence denotes Noticeably, in patients treated with HCQ alone, an association with increased overall mortality was observed [59].
T217 16613-16740 Sentence denotes In this study, the subjects included were only men and most of them were black, which may affect the generality of the results.
T218 16741-16852 Sentence denotes In addition, the patients who received HCQ or azithromycin were more severe, which may also affect the results.
T219 16853-17140 Sentence denotes 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).
T220 17141-17320 Sentence denotes 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%.
T221 17321-17551 Sentence denotes 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.
T222 17552-17666 Sentence denotes In this study, the sample size is large and includes patients with long-term, complex and ongoing hospitalization.
T223 17667-17857 Sentence denotes 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.
T224 17858-18050 Sentence denotes 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].
T225 18051-18106 Sentence denotes A total of 96,032 patients were included in this study.
T226 18107-18262 Sentence denotes 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.
T227 18263-18595 Sentence denotes 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.
T228 18596-18856 Sentence denotes 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].
T229 18857-19046 Sentence denotes 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.
T230 19047-19137 Sentence denotes This study included a large number of patients, but it is not a randomized clinical trial.
T231 19138-19355 Sentence denotes 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.
T232 19356-19622 Sentence denotes 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.
T233 19623-19944 Sentence denotes In summary, although CQ/HCQ appeared to exhibit a favorable effect on COVID-19 patients in some initial studies of small numbers of patients, the most recent studies with larger sample sizes revealed that CQ/HCQ exhibited no significant improvement of disease but even an increased overall mortality in COVID-19 patients.
T234 19945-20070 Sentence denotes The studies on the combination of HCQ or CQ and macrolides (azithromycin or clarithromycin) also showed conflicting findings.
T235 20071-20261 Sentence denotes Therefore, caution should be taken regarding the use of CQ/HCQ treatment in COVID-19 due to the uncertainty of efficacy, the potential adverse effects and the various defects in the studies.
T236 20262-20525 Sentence denotes According to the Chinese Clinical Trial Registry (ChiCTR) (http://www.chictr.org.cn/index.aspx) and the International Clinical Trials Registry Platform (ICTRP) (https://www.who.int/ictrp/en/), currently, there are more than 200 ongoing clinical trials for CQ/HCQ.
T237 20526-20688 Sentence denotes Current findings suggest that CQ/HCQ alone or in combination with macrolides should not be recommended for widespread use in COVID-19 (except in clinical trials).
T238 20689-20838 Sentence denotes Results from these ongoing prospective, randomized, controlled studies are required before these drugs are recommended for the treatment of COVID-19.