Id |
Subject |
Object |
Predicate |
Lexical cue |
T265 |
0-2 |
Sentence |
denotes |
7. |
T266 |
4-14 |
Sentence |
denotes |
Discussion |
T267 |
15-73 |
Sentence |
denotes |
At present, the COVID-19 pandemic is continuing worldwide. |
T268 |
74-171 |
Sentence |
denotes |
It is still an urgent need to find effective therapies and vaccines for treatment and prevention. |
T269 |
172-298 |
Sentence |
denotes |
CQ/HCQ have diverse biological activities, and their mechanisms against CoVs including SARS-CoV-2 are not yet fully clarified. |
T270 |
299-478 |
Sentence |
denotes |
Current studies show that CQ/HCQ can prevent receptor recognition by CoVs, inhibit endosome acidification, which interferes membrane fusion, and exhibit immunomodulatory activity. |
T271 |
479-565 |
Sentence |
denotes |
These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. |
T272 |
566-727 |
Sentence |
denotes |
A number of in vitro studies have revealed that CQ/HCQ have inhibitory effects on various CoVs, including SARS-CoV [12,13], MERS-CoV [10] and SARS-CoV-2 [16–18]. |
T273 |
728-830 |
Sentence |
denotes |
However, conflicting results also exist on the in vitro activity of CQ/HCQ against SARS-CoV-2 [17,18]. |
T274 |
831-1045 |
Sentence |
denotes |
Several clinical studies have shown that CQ/HCQ may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay the progression of the disease, with less serious adverse effects [48,50,57,58,]. |
T275 |
1046-1190 |
Sentence |
denotes |
However, previous studies showed that CQ had anti-Ebola virus activity in cell culture, but it had conflicting results in animal models [71,72]. |
T276 |
1191-1355 |
Sentence |
denotes |
In addition, CQ has shown beneficial results against chikungunya virus in vitro, but in animal models it aggravates the infection and lacks therapeutic effect [73]. |
T277 |
1356-1601 |
Sentence |
denotes |
More importantly, in recent studies the use of HCQ did not show any favorable effect on patients with COVID-19 and high-dose CQ treatment of severe COVID-19 patients may even increase the risks of mortality and QTc interval prolongation [49,55]. |
T278 |
1602-1689 |
Sentence |
denotes |
In addition, the optimal daily dose and duration of treatment course are not yet clear. |
T279 |
1690-1851 |
Sentence |
denotes |
One study suggested that the dose of HCQ should be 400 mg/2 times for 1 day, 200 mg/2 times/day for 4 days based on the physiological pharmacokinetic model [18]. |
T280 |
1852-2188 |
Sentence |
denotes |
A prospective study of HCQ on COVID-19 patients (13 cases) admitted to the ICU in France showed that the first daily dose of 800 mg/1 time for 1 day, and 200 mg/2 times/day for 7 days was recommended to maintain the HCQ treatment level (1–2 mg/l) based on physiologically pharmacokinetic (PBPK) models for COVID-19 patients in ICU [67]. |
T281 |
2189-2281 |
Sentence |
denotes |
Whether the dosage of CQ or HCQ should be varied according disease severity is also unclear. |
T282 |
2282-2397 |
Sentence |
denotes |
A rodent study showed that CQ could exert anti-HCoV-OC43 activity transplacentally or by way of maternal milk [14]. |
T283 |
2398-2553 |
Sentence |
denotes |
However, in humans, the efficacy of CQ in the prevention and treatment of SARS-CoV-2 infection to both the mother and the child remains to be investigated. |
T284 |
2554-2731 |
Sentence |
denotes |
Clinical trials in France showed that HCQ combined with azithromycin could enhance the virus clearance [50], but the subsequent reports did not support this combination [59,61]. |
T285 |
2732-2902 |
Sentence |
denotes |
Furthermore, CQ/HCQ alone or in combination with a macrolide induced high rate of adverse effects, especially prolonged QTc, in the use for COVID-19 treatment [61,68,69]. |
T286 |
2903-3246 |
Sentence |
denotes |
Therefore, current data are not sufficient enough to support the routine use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken for the application of CQ/HCQ, alone or in combination with other drugs, in COVID-19 before the conclusive findings are obtained by well-designed, multicenter, randomized, controlled studies. |