LitCovid-sentences  

PMC:7652766 / 99378-109033 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T486 0-34 Sentence denotes Chloroquine and Hydroxychloroquine
T487 35-188 Sentence denotes Chloroquine and hydroxychloroquine have been used worldwide for more than 70 years, and they are part of the WHO model list of essential medicines (346).
T488 189-527 Sentence denotes They were synthesized specifically for the treatment and chemoprevention of malaria, but their immunomodulatory activity led these drugs to be used against autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and other inflammatory rheumatic diseases; they also show broad-spectrum antiviral effects (347–349).
T489 528-714 Sentence denotes Regarding the chemical structure, hydroxychloroquine differs from chloroquine in the presence of a hydroxyl group at the end of the side chain: the N-ethyl substituent is β-hydroxylated.
T490 715-970 Sentence denotes Both drugs have similar pharmacokinetics, with rapid gastrointestinal absorption and renal elimination, but different clinical indications and toxic doses, in which hydroxychloroquine is less toxic and more clinically used in the malaria model (348, 350).
T491 971-1099 Sentence denotes The action mechanism of these drugs has direct molecular effects on lysosomal activity, autophagy, and signaling pathways (347).
T492 1100-1298 Sentence denotes As antivirals, chloroquine is known to block SARS-CoV-1-infection by increasing endosomal pH required for virus entry, as well as interfering with the glycosylation of cellular receptors (351, 352).
T493 1299-1595 Sentence denotes The possible mechanism against SARS-CoV-2 is the inhibition of virus entry by altering the glycosylation of ACE2, reducing the binding efficiency between ACE2 in host cells and the S protein on the surface of the SARS-CoV-2, thus preventing the virus from binding to target cells (348, 351, 353).
T494 1596-1725 Sentence denotes In addition to a potent antiviral inhibition, the immunomodulatory activity of these drugs is well established in the literature.
T495 1726-2180 Sentence denotes Proposed effects of chloroquine on the immune system include increasing the export of soluble antigens into the cytosol of dendritic cells, the blocking of TLR7 and TLR9 signaling, thus reconstructing CD8+ cytotoxic viral response, and inhibiting and/or reducing the production of inflammatory cytokines like IL-1, IL-6, TNF, and IFN-α (347, 354–359), which has an important role in the immunopathogenesis of COVID-19, as previously reported in item 4.1.
T496 2181-2336 Sentence denotes In vitro studies on SARS-CoV-2 have demonstrated the low-dose action of these drugs, having found the lowest half-maximal effective concentrations (EC50s).
T497 2337-2443 Sentence denotes In addition, their association with azithromycin significantly inhibited viral replication (326, 360–362).
T498 2444-2696 Sentence denotes In humans, a study by Gao, Tian, and Yang (363) showed that patients treated with chloroquine phosphate had inhibited exacerbation of pneumonia, improving lung imaging findings, promoting a virus-negative conversion, and shortening the COVID-19 course.
T499 2697-2939 Sentence denotes The association of hydroxychloroquine with other drugs is also suggested, with emphasis on studies using azithromycin, a broad-spectrum macrolide antibiotic primarily used to treat respiratory, enteric, and genitourinary bacterial infections.
T500 2940-3089 Sentence denotes Despite not yet being approved for antiviral therapy, it has been studied in vitro and in clinical trials for activity against several viruses (364).
T501 3090-3254 Sentence denotes Gautret et al. (365) demonstrated the effectiveness of the hydroxychloroquine-azithromycin combination in a non-randomized clinical trial with 36 COVID-19 patients.
T502 3255-3414 Sentence denotes A 57.1% rate of cure was attributed to the patients treated with hydroxychloroquine, however, when combined with azithromycin, 100% of the patients were cured.
T503 3415-3573 Sentence denotes The authors suggested a synergistic effect of the drug combination since both were reported to have antiviral and immunomodulatory activity in the literature.
T504 3574-3828 Sentence denotes Gautret et al. (366) conducted another analysis to provide evidence of a beneficial effect of co-administration of hydroxychloroquine with azithromycin in a non-comparative and uncontrolled observational study with 80 mildly infected SARS-CoV-2 patients.
T505 3829-4048 Sentence denotes The hydroxychloroquine/azithromycin treatment showed that 81.3% of the patients had a favorable result with a rapid decrease in nasopharyngeal viral load at day 8 (93%), reducing the mean length of stay in the hospital.
T506 4049-4152 Sentence denotes Arshad et al. (367) performed a multicenter observational study, which included 2541 COVID-19 patients.
T507 4153-4348 Sentence denotes Patients were separated into four groups: untreated (n = 409), treated with hydroxychloroquine (n = 1202), the association of hydroxychloroquine and azithromycin, and azithromycin only (n = 147).
T508 4349-4568 Sentence denotes The authors suggested that the treatment with hydroxychloroquine alone and in combination with azithromycin was associated with a reduction in the hazard ratio for death when compared with receipt of neither medication.
T509 4569-4774 Sentence denotes However, a lot of controversy has been raised about these data, and many important limitations of this study were considered by several authors (368–373), threatening the validity of the reported findings.
T510 4775-5066 Sentence denotes Among these, there is the potential for immortal time bias and selection bias, the administration of corticosteroids in most patients treated with hydroxychloroquine than in other groups, and a disproportionately high share of patients with cardiovascular comorbidity in the untreated group.
T511 5067-5255 Sentence denotes Seeking to analyze the efficacy of early treatment using hydroxychloroquine and azithromycin, Million et al. (374) carried out a retrospective study with 1061 SARS-CoV-2 infected patients.
T512 5256-5418 Sentence denotes In the study, 91.7% of the patients reached good clinical results and virological cure within 10 days, while 4.3% had a poor outcome associated with advanced age.
T513 5419-5524 Sentence denotes However, it is worth mentioning that the study did not include a control group to establish a comparison.
T514 5525-5767 Sentence denotes To assess the use of hydroxychloroquine as a prophylactic measure, Boulware et al. (375) performed a randomized, double-blind trial in adults who had been exposed to individuals diagnosed with COVID-19, either in the home or work environment.
T515 5768-5863 Sentence denotes The authors found that postexposure prophylaxis did not prevent the development of the disease.
T516 5864-6107 Sentence denotes An important question that may be considered about chloroquine and its derivate is the numerous adverse effects reported, such as nausea, pruritus, headache, hypoglycemia, neuropsychiatric effects, and idiosyncratic hypersensitivity reactions.
T517 6108-6272 Sentence denotes In long-term treatments, effects such as retinopathy, vacuolar myopathy, neuropathy, restrictive cardiomyopathy, and cardiac conduction disorders are also reported.
T518 6273-6416 Sentence denotes Furthermore, its concomitant use with azithromycin may predispose patients to arrhythmias (213), which represents a major negative implication.
T519 6417-6562 Sentence denotes Huang et al. (376) conducted a randomized clinical trial with 22 patients in China to compare the effects of chloroquine and lopinavir/ritonavir.
T520 6563-6766 Sentence denotes Even though chloroquine led to some clinical improvement, half of the patients experienced adverse effects such as vomiting, abdominal pain, nausea, diarrhea, skin rashes, cough, and shortness of breath.
T521 6767-7106 Sentence denotes Satlin et al. (377), Magagnoli et al. (378), Rosenberg et al. (379), and Ip et al. (380) reported that treatment with hydroxychloroquine, azithromycin, or both were not associated with a survival benefit among patients and there were no significant differences in mortality for patients receiving hydroxychloroquine during hospitalization.
T522 7107-7319 Sentence denotes Similarly, Mahévas et al. (381) analyzed the efficacy of hydroxychloroquine in patients hospitalized with coronavirus pneumonia who needed oxygen but not intensive care, through a comparative observational study.
T523 7320-7387 Sentence denotes 181 patients were analyzed, 84 of whom received hydroxychloroquine.
T524 7388-7658 Sentence denotes Data showed there was no effect on reducing admissions to intensive care or deaths on day 21 after hospital admission and the hydroxychloroquine treatment did not have any effect on survival without acute respiratory distress syndrome on day 21 after hospital admission.
T525 7659-7875 Sentence denotes Tang et al. (382) carried out a multicenter, open, randomized, and controlled clinical trial evaluating 150 patients admitted with confirmed mild to severe COVID-19; of these, 75 were treated with hydroxychloroquine.
T526 7876-7968 Sentence denotes The authors demonstrated that treatment does not contribute to the elimination of the virus.
T527 7969-8241 Sentence denotes Borba et al. (383) conducted a phase IIb, double-blind, randomized clinical trial comparing the effects of high doses (600 mg/twice daily for 10 days) and low doses (450 mg twice daily at day 1 and once daily for 4 days) of chloroquine in 81 and 40 patients, respectively.
T528 8242-8357 Sentence denotes The results did not evidence lower viral load in respiratory secretions, not even in combination with azithromycin.
T529 8358-8464 Sentence denotes The mortality rate for the high-dose group was over twice as high as the low-dose group (39.0% vs. 16.0%).
T530 8465-8690 Sentence denotes Additionally, some patients, mainly in the high-dose group, showed adverse effects, such as increased creatine phosphokinase (CK) and CK-MB, while the high-dosage group exhibited more corrected QT (QTc) interval prolongation.
T531 8691-8746 Sentence denotes Neither of the dosages was able to influence lethality.
T532 8747-8843 Sentence denotes The authors concluded that critically ill patients should not receive chloroquine at high doses.
T533 8844-9082 Sentence denotes In the meantime, a cohort study with 201 patients showed that the use of chloroquine or hydroxychloroquine combined with azithromycin generated a higher increase in QT prolongation than chloroquine or hydroxychloroquine monotherapy (384).
T534 9083-9280 Sentence denotes More recently, another large observational study involving 1376 cases of COVID-19 from New York found no significant association between the use of hydroxychloroquine and intubation or death (385).
T535 9281-9454 Sentence denotes Currently, chloroquine and hydroxychloroquine are the most largely studied compounds in the context of COVID-19 treatment, encompassing at least 320 ongoing clinical trials.
T536 9455-9655 Sentence denotes However, considering that more recent studies failed to prove any favorable effect of their use in COVID-19 patients, the WHO discontinued the study of hydroxychloroquine in the Solidarity Trial (13).