LitCovid-sentences  

PMC:7696151 / 25730-34349 JSONTXT 3 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T179 0-210 Sentence denotes Coronaviruses, belonging to the Coronaviridae family, are enveloped positive-sense single-stranded RNA viruses highly distributed in humans and vertebrates like bats, which are proposed as their main reservoir.
T180 211-393 Sentence denotes Specifically, Coronavirus Disease of 2019 (COVID-19) was first identified in December 2019 in Wuhan, the capital city of Hubei (China), and it is caused by the SARS-CoV-2 virus [49].
T181 394-568 Sentence denotes Since COVID-19 has spread rapidly in many countries, it has quickly become a global pandemic, so it is necessary to develop drugs able to exert antiviral activity against it.
T182 569-664 Sentence denotes A recent study showed HCQ in vitro antiviral activity against SARS-CoV-2 (EC50 = 0.72 μM) [50].
T183 665-866 Sentence denotes HCQ seemed to be able to inhibit the first step of the viral replication cycle by interfering with the link between spike (S) viral protein and the angiotensin-converting enzyme 2 (ACE-2) receptor [8].
T184 867-1026 Sentence denotes It would also appear that HCQ was able to induce changes in cell membrane pH resulting in reduced viral entry and inhibition of the last stages of replication.
T185 1027-1149 Sentence denotes Moreover, HCQ may abolish the cytokine storm related to the advanced stages of COVID-19 through immunomodulatory activity.
T186 1150-1259 Sentence denotes To date, several clinical studies are underway to evaluate the efficacy of HCQ for the treatment of COVID-19.
T187 1260-1406 Sentence denotes In a randomized clinical trial conducted in China, 62 patients with COVID-19 were randomly assigned to two groups: the control and the HCQ groups.
T188 1407-1645 Sentence denotes Either group received standard treatment including antiviral agents, oxygen therapy, immunoglobulin, and antibacterial agents, with or without corticosteroids, but patients in the HCQ group also received oral HCQ 400 mg/day for five days.
T189 1646-1791 Sentence denotes During treatment, clinical characteristics, clinical recovery time (TTCR), and radiological results were assessed to determine the effect of HCQ.
T190 1792-2041 Sentence denotes It was seen that in the HCQ group, the recovery time of body temperature was shorter than in the control group and that the cough remission time was also significantly decreased, while only patients in the control group progressed to severe illness.
T191 2042-2138 Sentence denotes Furthermore, in the HCQ group, 61.3% of patients showed significant absorption of pneumonia [6].
T192 2139-2271 Sentence denotes In another open-label non-randomized French clinical trial, the efficiency of HCQ in reducing the viral count was also demonstrated.
T193 2272-2328 Sentence denotes In this study, 36 subjects were divided into two groups:
T194 2329-2424 Sentence denotes 16 patients for the control group and 20 subjects for HCQ who were administered 600 mg/day HCQ.
T195 2425-2590 Sentence denotes Among the HCQ group, six patients also received 500 mg of AZM for the first day, followed by 250 mg/day for the next four days to prevent super bacterial infections.
T196 2591-2736 Sentence denotes PCR results from nasopharyngeal samples were negative for 70% of patients treated with HCQ and 12.5% in the control group (p = 0.001) on day six.
T197 2737-2985 Sentence denotes Furthermore, when the effect of HCQ as monotherapy was compared to that of HCQ + AZM, it was found that at day six, 100% of HCQ + AZM treated subjects were virologically negative compared with 57.1% of patients treated with HCQ as monotherapy [32].
T198 2986-3203 Sentence denotes These results suggest a synergistic effect between HCQ and AZM and are supported by an uncontrolled non-comparative observational study conducted by the same France group, in a cohort of 80 slightly infected patients.
T199 3204-3371 Sentence denotes In this study, HCQ + AZM treated people were 83% virologically negative on day 7 and 93% on day 8; after 10 days of treatment, only 2 subjects still remain contagious.
T200 3372-3496 Sentence denotes Furthermore, the average duration of hospitalization was found to be 4.6 days after the administration of HCQ plus AZM [33].
T201 3497-3578 Sentence denotes However, these last two studies have a limit, as Gautret et al. carried both out.
T202 3579-3754 Sentence denotes In particular, in the first study, data are available up to 6 days despite the planned 10 days, and in the second study, 6 patients from the previous study were also included.
T203 3755-3953 Sentence denotes Gautret also conducted a retrospective analysis of 1061 cases in which, after treatment with HCQ + AZM, good virological care and clinical outcomes were found in 973 patients (91.7%) within 10 days.
T204 3954-4123 Sentence denotes A prolonged viral carriage was observed in only 47 (4.4%) subjects with a high viral load at the moment of hospitalization, but on day 10 the viral culture was negative.
T205 4124-4177 Sentence denotes Finally, all but one on day 15 were PCR cleared [51].
T206 4178-4313 Sentence denotes By contrast, there are results obtained by several clinical studies that dismiss the possible use of HCQ for the treatment of COVID-19.
T207 4314-4659 Sentence denotes In particular, a prospective study on 11 severe COVID-19 infected patients treated with the same dosage used by Gautret et al. (600 mg/day HCQ and 500 mg AZM for the first day followed by 250 mg/day from day 2 to 5) was shown to provide no evidence of clinical benefits or a strong antiviral activity through the combination of HCQ and AZM [34].
T208 4660-4875 Sentence denotes The ineffectiveness of HCQ has also been declared in a multicenter, open-label, randomized controlled trial involving 150 hospitalized infected patients (148 with mild or moderate disease and 2 with severe disease).
T209 4876-5074 Sentence denotes All subjects were divided into two groups (in a 1:1 ratio): the control group that received only SOC, consisting of antiviral, glucocorticoid, and antiviral, and the group treated with HCQ plus SOC.
T210 5075-5230 Sentence denotes The administrated dose of HCQ consisted of 200 mg/day for the first three days, followed by 800 mg/day as maintained dosage until the end of the treatment.
T211 5231-5370 Sentence denotes After 28 days of treatment, there was no significant difference in SARS-CoV-2 negative conversion in either the HCQ + SOC or the SOC group.
T212 5371-5561 Sentence denotes Similarly, there were no significant differences in the median time to negative conversion and the probability of symptom alleviation within 28 days between HCQ + SOC and the SOC group [35].
T213 5562-5709 Sentence denotes Another multicenter, randomized controlled Egyptian trial evaluated, in 194 subjects with COVID-19, the safety and efficacy of HCQ compared to SOC.
T214 5710-5936 Sentence denotes In terms of mechanical ventilation need and mortality, the addition of HCQ (400 mg twice daily (in day 1) followed by 200 mg tablets twice daily) to SOC was not associated with an improvement of COVID-19 patients’ health [36].
T215 5937-6061 Sentence denotes These results were confirmed by a recent randomized, double-blind, placebo-controlled trial conducted in the USA and Canada.
T216 6062-6296 Sentence denotes In this study, 419 early and mild COVID-19 subjects were randomly assigned to two groups, the HCQ group treated with 800 mg HCQ once, followed by 600 mg in 6 to 8 h, then 600 mg daily for 4 more days, and the placebo or control group.
T217 6297-6566 Sentence denotes Within 14 days of treatment, there was no change in the severity of symptoms in non-hospitalized patients between the HCQ group and the placebo group (difference in symptom severity: relative, 12%; absolute, −0.27 points (95% CI, −0.61 to 0.07 points); p = 0.117) [37].
T218 6567-6762 Sentence denotes Likewise, 2 studies carried out by Mahévas et al. supported the ineffectiveness of HCQ and highlighted that HCQ administration to COVID-10 patients was highly related to ECG modification [38,39].
T219 6763-6965 Sentence denotes ECG modification, resulting in QT-interval prolongation, is a characteristic side effect associated with HCQ treatment that has been shown in several clinical studies on patients infected with COVID-19.
T220 6966-7165 Sentence denotes In particular, the risk of QT-interval prolongation was increased when HCQ was associated with AZM, as demonstrated in a cohort of 84 patients who received 400 mg twice-daily HCQ plus 500 mg/day AZM.
T221 7166-7341 Sentence denotes In these patients, on day 3.6 ± 1.6 of therapy, the EGC showed a QTc prolongation from a baseline average of 435 ± 24 ms (mean ± SD) to a maximal average value of 463 ± 32 ms.
T222 7342-7510 Sentence denotes Moreover, in nine subjects (11%) there was a severe prolongation of QTc to > 500 ms (baseline average of 447 ± 30 ms to 527 ± 17 ms (p < 0.01 (one-sample t-test)) [52].
T223 7511-7624 Sentence denotes This complication was also confirmed in a retrospective study of 251 COVID-19 patients treated with HCQ/AZM [53].
T224 7625-7752 Sentence denotes It seems that a predictor of extreme QTc prolongation was renal failure and that its incidence increased with longer treatment.
T225 7753-8030 Sentence denotes The probability of QTc prolongation may also increase in the presence of other factors such as previous cardiovascular diseases, metabolic degeneration (hypoxia, pH, multiorgan system failure, and electrolyte abnormalities), age, and sex (females seem to be more at risk) [54].
T226 8031-8316 Sentence denotes Therefore, since QTc prolongation to more than 500 ms is known to be associated with a high risk for malignant arrhythmia and fatal stroke, recent guidance suggests the ECG screening with QTc evaluation in COVID-19-infected patients treated with novel therapies including HCQ/AZM [55].
T227 8317-8619 Sentence denotes It has also been suggested that the use of drugs that block late sodium channels (mexiletine or lidocaine) and close attention to serum electrolytes, in addition to the evaluation of heart rate and QT intervals, may allow the administration of HCQ/AZM even in subjects with prolonged QT intervals [54].