PMC:7195088 / 48271-53047 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T375 0-66 Sentence denotes Question 3. should chloroquine/hydroxychloroquine be administered?
T376 67-246 Sentence denotes The rationale of using chloroquine for treating COVID-19 patients is based on two potential and non–mutually exclusive mechanisms: antiviral activity and immunomodulatory effects.
T377 247-580 Sentence denotes With regard to antiviral activity, chloroquine has been shown to inhibit various viruses in cell cultures, including SARS-CoV-1 and SARS-CoV-2, possibly via pH-dependent inhibition of virus–endosome fusion and/or posttranslational modifications of CoV proteins, although other mechanisms may also contribute [[32], [33], [34], [35]].
T378 581-929 Sentence denotes With regard to the immunomodulatory effects, the attenuated production of tumor necrosis factor alpha, interleukin (IL)-6 and interferons that follows the administration of chloroquine might help counteract an exaggerated proinflammatory response, which is thought to contribute to the organ damage observed in SARS-CoV-2–infected patients [36,37].
T379 930-1085 Sentence denotes However, some authors have pointed out that an unfavourable immunomodulatory effect cannot be excluded, based on a reduced T helper 2 differentiation [38].
T380 1086-1308 Sentence denotes In our opinion, hydroxychloroquine should be preferred over chloroquine because of its less toxic profile (reduced ocular toxicity and fewer drug interactions) and its more potent in vitro activity against SARS-CoV-2 [39].
T381 1309-1568 Sentence denotes Recently, Cortegiani et al. [40] reviewed the available information on ongoing case series, comparative observational studies and RCT evaluating the use of chloroquine or hydroxychloroquine in patients with COVID-19 and registered in Chinese or US registries.
T382 1569-1621 Sentence denotes They found 23 studies, all being conducted in China.
T383 1622-1811 Sentence denotes However, in the few weeks after the paper was made available online (10 March 2020), the number of registered studies being conducted in countries other than China has multiplied (Table 2).
T384 1812-2092 Sentence denotes In particular, results of registered RCT are necessary to guide (or discourage) the use of chloroquine/hydroxychloroquine in two different settings: prophylaxis of exposed individuals and treatment of proven cases, stratified for the severity of clinical presentation/progression.
T385 2093-2235 Sentence denotes In the meantime, a small controlled nonrandomized study of COVID-19 patients treated with hydroxychloroquine has been recently published [41].
T386 2236-2489 Sentence denotes In this study, Gautret et al. enrolled 26 COVID-19 patients to receive 200 mg of hydroxychloroquine every 8 hours for 10 days, whereas a total of 16 patients who denied consent as well as untreated patients from another centre were included as controls.
T387 2490-2571 Sentence denotes Of note, six patients treated with hydroxychloroquine also received azithromycin.
T388 2572-2706 Sentence denotes The primary endpoint was virologic clearance (based on results of real-time PCR on nasopharyngeal specimens) at day 6 after inclusion.
T389 2707-3062 Sentence denotes At day 6, 70% (14/20) of hydroxychloroquine-treated patients were virologically cured versus 12.5% (2/16) in the control group (p 0.001), although it cannot be excluded that selection bias and baseline virus load played a role in influencing results, thereby biasing results towards observing a favourable effect of hydroxychloroquine administration [42].
T390 3063-3294 Sentence denotes Furthermore, the opposite results (apparent absence of reduction of virus clearance) were recently described by another French group (albeit in a tiny sample size of 11 patients receiving hydroxychloroquine plus azithromycin) [43].
T391 3295-3643 Sentence denotes Uncertainty also surrounds the more marked positive effect observed in patients receiving azithromycin in addition to hydroxychloroquine in the study by Gautret et al., especially because of the very small number of patients in the combined treatment subgroup and the possible increased risk of QT prolongation by combining the two drugs (Table 3).
T392 3645-3665 Sentence denotes Question 3 statement
T393 3666-3924 Sentence denotes Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic function, renal function and QT prolongation.
T394 3925-4133 Sentence denotes This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled nonrandomized study.
T395 4134-4306 Sentence denotes However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality.
T396 4307-4431 Sentence denotes For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies.
T397 4432-4541 Sentence denotes When this is unfeasible, off-label use may be considered according to local protocols and consent procedures.
T398 4542-4738 Sentence denotes In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies.
T399 4739-4776 Sentence denotes The same applies to prophylactic use.