LitCovid-sentences  

PMC:7195088 / 39979-48269 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T302 0-52 Sentence denotes Question 2. should antiviral agents be administered?
T303 53-334 Sentence denotes Several antiviral agents have demonstrated in vitro activity against SARS-CoV-2 or other coronaviruses, but currently there are no approved antiviral agents for coronavirus-related diseases, and there are still no favourable efficacy results from RCT available at the present time.
T304 335-483 Sentence denotes Lopinavir is a protease inhibitor used for the treatment of HIV patients, administered in combination with ritonavir to improve its serum half-life.
T305 484-785 Sentence denotes On the basis of its activity against SARS-CoV-1 and/or Middle East respiratory syndrome (MERS)-CoV observed in in vitro and animal studies [[19], [20], [21]], lopinavir/ritonavir (LPV/RTV) was compared to supportive care alone for the treatment of COVID-19 patients in an open-label RCT in China [22].
T306 786-1034 Sentence denotes The primary time-to-event endpoint was clinical improvement from randomization (defined as a composite of discharge from the hospital or improvement of two points on a seven-category ordinal scale, ranging from no need of hospitalization to death).
T307 1035-1138 Sentence denotes Overall, 199 patients were enrolled (99 and 100 in the LPV/RTV and supportive care arms, respectively).
T308 1139-1336 Sentence denotes No differences were observed in the intent-to-treat population with regard to clinical improvement (hazard ratio 1.24 with standard of care as reference, 95% confidence interval (CI) 0.90 to 1.72).
T309 1337-1605 Sentence denotes In addition, no associations were observed with regard to 28-day mortality, although a smaller number of deaths were registered in the LPV/RTV arm (19.2% vs. 25.0% in investigational and comparator arms, respectively; percentage difference −5.8%, 95% CI −17.3 to 5.7).
T310 1606-2252 Sentence denotes Although some important considerations preclude a definite judgement on the possible efficacy of LPV/RTV (e.g. some major limitations are the open-label nature of the trial and the fact that LPV/RTV was initiated late with respect to the onset of symptoms; see question 7), especially in the case of early therapy initiation, the results of this RCT provide evidence currently discouraging the use of LPV/RTV (or of other protease inhibitors such as darunavir) in COVID-19 patients (also considering the potential side effects; Table 3 ), unless favourable results from other ongoing RCT in specific subgroups of patients are available (Table 2).
T311 2253-2467 Sentence denotes Furthermore, harmful drug interactions of antivirals with other drugs (such as hydroxychloroquine) cannot be excluded a priori because there are currently no large clinical data about the use of these combinations.
T312 2468-2635 Sentence denotes Table 3 Known adverse events of marketed anti-infective and anti-inflammatory drugs mostly provided as off-label treatments in the first phase of the COVID-19 pandemic
T313 2636-2655 Sentence denotes Drug Adverse events
T314 2656-2741 Sentence denotes Lopinavir/ritonavir • Hypercholesterolaemia and increased serum triglycerides (3–39%)
T315 2742-2785 Sentence denotes • Increased γ-glutamyl transferase (10–29%)
T316 2786-2837 Sentence denotes • Diarrhoea (7–28%; greater with once-daily dosing)
T317 2838-2871 Sentence denotes • Increased serum ALT (grade 3/4:
T318 2872-2878 Sentence denotes 1–11%)
T319 2879-2895 Sentence denotes • Nausea (5–16%)
T320 2896-2937 Sentence denotes • Upper respiratory tract infection (14%)
T321 2938-2962 Sentence denotes • Abdominal pain (1–11%)
T322 2963-2980 Sentence denotes • Vomiting (2–7%)
T323 2981-2995 Sentence denotes • Fatigue (8%)
T324 2996-3042 Sentence denotes • Increased serum amylase and/or lipase (3–8%)
T325 3043-3060 Sentence denotes • Headache (2–6%)
T326 3061-3078 Sentence denotes • Skin rash (≤5%)
T327 3079-3104 Sentence denotes • Neutropenia (grade 3/4:
T328 3105-3110 Sentence denotes 1–5%)
T329 3111-3125 Sentence denotes • Anxiety (4%)
T330 3126-3142 Sentence denotes • Insomnia (≤4%)
T331 3143-3213 Sentence denotes Chloroquine/hydroxychloroquine • Retinopathy (4% of treated patients)a
T332 3214-3465 Sentence denotes • Other adverse effects with unknown frequency included Stevens-Johnson syndrome, abdominal pain, diarrhoea, nausea, vomiting, agranulocytosis, leukopenia, thrombocytopenia, abnormal hepatic function tests, acute hepatic ailure, myopathy, bronchospasm
T333 3466-3572 Sentence denotes • Risk of prolonged QT interval, further increased when administered with fluoroquinolones or azithromycin
T334 3573-3628 Sentence denotes Tocilizumab • Increased serum ALT (≤36%) and AST (≤22%)
T335 3629-3664 Sentence denotes • Increased LDL cholesterol (9–10%)
T336 3665-3698 Sentence denotes • Injection site reaction (4–10%)
T337 3699-3722 Sentence denotes • Neutropenia (grade 3:
T338 3723-3750 Sentence denotes 2–7% of all adult patients)
T339 3751-3768 Sentence denotes • Headache (1–7%)
T340 3769-3790 Sentence denotes • Hypertension (1–6%)
T341 3791-3807 Sentence denotes • Dizziness (3%)
T342 3808-3830 Sentence denotes • Hypothyroidism (<2%)
T343 3831-3852 Sentence denotes • Abdominal pain (2%)
T344 3853-3889 Sentence denotes • Oral mucosa or gastric ulcers (2%)
T345 3890-4063 Sentence denotes • Infections due to Pneumocystis, Mycobacterium tuberculosis and varicella zoster have been reported after tocilizumab, but their prevalence has not been clearly established
T346 4064-4108 Sentence denotes Anakinra • Injection site reactionb (24–71%)
T347 4109-4222 Sentence denotes • Antibody development (up to 50% of the patients but no correlation of antibody development and adverse effects)
T348 4223-4255 Sentence denotes • Headache and vomiting (12–14%)
T349 4256-4277 Sentence denotes • Arthralgia (10–12%)
T350 4278-4294 Sentence denotes • Fever (10–12%)
T351 4295-4389 Sentence denotes • Haematologic disorder including eosinophilia, leukopenia and change in platelet count (2–9%)
T352 4390-4419 Sentence denotes • Nausea and diarrhoea (7–8%)
T353 4420-4447 Sentence denotes • Serious infectionc (2–3%)
T354 4448-4581 Sentence denotes Off-label drugs mostly provided in Italy during the first phase of the COVID-19 pandemic according to the authors' direct experience.
T355 4582-4711 Sentence denotes ALT, alanine aminotransferase; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; LDL, low-density lipoprotein.
T356 4712-4852 Sentence denotes a Serum concentration dependent adverse effect; early changes are generally reversible but may progress despite discontinuation if advanced.
T357 4853-4921 Sentence denotes b Injection site reactions were considered serious in 2–3% of cases.
T358 4922-5005 Sentence denotes c Serious infections included cellulitis, pneumonia, and bone and joint infections.
T359 5006-5261 Sentence denotes Remdesivir is an investigational nucleotide analogue undergoing clinical development for Ebola and showing in vitro activity against coronaviruses (SARS-CoV-2, SARS-CoV-1 and MERS-CoV) and favourable effects in animal MERS models [[23], [24], [25], [26]].
T360 5262-5365 Sentence denotes Following these promising preclinical findings, RCT in COVID-19 patients have been initiated (Table 2).
T361 5366-5597 Sentence denotes However, pending their results, and considering the investigational nature of the drug, access to remdesivir outside RCT is currently provided only within strictly regulated and limited compassionate-use/expanded-access frameworks.
T362 5598-5757 Sentence denotes Oseltamivir and zanamivir are neuraminidase inhibitors used for treating influenza which are also being tested in RCT for treating COVID-19 patients (Table 2).
T363 5758-6067 Sentence denotes However, no apparent activity of oseltamivir and zanamivir has previously been observed against SARS-CoV-1 in vitro [27], and the fact that up to 76% of the first critically ill patients with COVID-19 received oseltamivir may also be related to the suspicion of infection (or coinfection) with influenza [28].
T364 6068-6245 Sentence denotes Overall, this information is currently insufficient for supporting the use of these agents in COVID-19 patients unless in the presence of suspected/proven concomitant influenza.
T365 6246-6499 Sentence denotes Other antiviral agents currently being investigated in RCT for the treatment of COVID-19 patients are favipiravir, an RNA-dependent RNA polymerase inhibitor with anti-influenza activity, and umifenovir, and anti-influenza membrane fusion inhibitor [29].
T366 6500-6862 Sentence denotes Even though these two agents attracted important media attention in the last few months, and even though there were some favourable preliminary results, especially for favipiravir, released as preprints, we advocate caution in using these agents outside investigational studies until completion of the standard peer-review processes of the first released trials.
T367 6863-7328 Sentence denotes For example, in a recent RCT comparing 120 COVID-19 patients treated with favipiravir versus 120 COVID-19 patients receiving umifenovir, higher rates of clinical recovery were observed in patients receiving favipiravir, but it is of note that the all-cause mortality was 0 in the entire study population, making it uncertain whether, if confirmed, these favourable results may be extrapolated to relevant survival endpoints in critically ill COVID-19 patients [30].
T368 7329-7469 Sentence denotes Finally, antiviral activity against SARS-CoV-2 in vitro has been recently reported for ivermectin, but clinical data are still lacking [31].
T369 7471-7491 Sentence denotes Question 2 statement
T370 7492-7622 Sentence denotes At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients.
T371 7623-7767 Sentence denotes This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available.
T372 7768-8000 Sentence denotes Although promising in preclinical studies, remdesivir should be currently provided for treating COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature.
T373 8001-8182 Sentence denotes Pending high-level supporting evidence, favipiravir and umifenovir should not be provided outside RCT, at least in those countries where they are not approved for other indications.
T374 8183-8290 Sentence denotes Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.