LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T424 0-10 Sentence denotes Antivirals
T425 11-258 Sentence denotes Due to the large amount of experimental and clinical studies assessing the effectiveness of antiviral therapy against SARS-CoV-2, we have seen the importance of this class of drugs in reducing the viral load peak at the beginning of the infection.
T426 259-489 Sentence denotes Evidence from laboratory, animal, and clinical studies demonstrate that the use of associated or isolated antivirals can delay the progression of lung lesions and decrease the possibility of respiratory transmission of SARS-CoV-2.
T427 490-646 Sentence denotes In this study, we selected the following most promising treatment options: lopinavir/ritonavir, arbidol, ribavirin, remdesivir, favipiravir, and type I IFN.
T428 647-1038 Sentence denotes In the context of discovering new drugs, it is efficient to test the efficacy of existing antiviral drugs regarding the treatment of related viral infections. After the emergence of SARS in 2003, the screening of approved drugs identified an effective SARS-CoV-2 antiviral-drug candidate: the combination of the human immunodeficiency virus (HIV) protease inhibitors lopinavir and ritonavir.
T429 1039-1194 Sentence denotes However, lopinavir has insufficient oral bioavailability for significant therapeutic activity due to rapid catabolism by the cytochrome P450 enzyme system.
T430 1195-1407 Sentence denotes Thus, ritonavir is a cytochrome P450 and glycoproteins inhibitor, which increases the lopinavir plasma half-life, enhancing the pharmacokinetic and pharmacodynamic activities against the viral HIV-protease (303).
T431 1408-1718 Sentence denotes Chu et al. (304) described the possible mechanism of action of these drugs on SARS-CoV-1, suggesting that they act by inhibiting intracellular viral multiplication, preventing the action of the protease enzyme, which leads to the formation of an immature and less infectious virus with no ability to replicate.
T432 1719-1864 Sentence denotes Choy et al. (305) were successful at demonstrating the antiviral effect of lopinavir against SARS-CoV-2, but this was not the case for ritonavir.
T433 1865-2030 Sentence denotes In turn, Kang et al. (306) found a lower viral load in infected SARS-CoV-2 Vero cells treated with lopinavir/ritonavir in relation to the untreated infected control.
T434 2031-2308 Sentence denotes Although no consensus has been reached on its efficacy, dosage, or administration period, the literature includes some case reports, case series, and observational studies reporting a protective effect of the lopinavir/ritonavir combination in COVID-19 patients (110, 307–312).
T435 2309-2539 Sentence denotes Conversely, Cao et al. (313) conducted a controlled open‐label study with 199 hospitalized severe COVID‐19 patients randomly divided into two groups: a standard care group and a lopinavir/ritonavir treatment group (400 mg/100 mg).
T436 2540-2726 Sentence denotes No benefit was observed in the lopinavir/ritonavir treatment group, showing no significant results for faster clinical improvement, lower mortality, or decreased viral RNA detectability.
T437 2727-2933 Sentence denotes Although there are 85 clinical trials in progress testing lopinavir/ritonavir associated with other drugs on SARS-CoV-2 and/or COVID-19, WHO stopped the study of lopinavir/ritonavir in the Solidarity Trial.
T438 2934-3151 Sentence denotes Deng et al. (312) have studied the association of lopinavir/ritonavir with arbidol treatment and demonstrated a significant improvement in COVID-19 patients compared with a group treated only with lopinavir/ritonavir.
T439 3152-3286 Sentence denotes Arbidol (umifenovir) is a broad-spectrum antiviral and immunomodulatory compound used to treat influenza and many other viruses (314).
T440 3287-3592 Sentence denotes Analyses of molecular dynamics and structure-guided drug-binding have suggested an efficiency of arbidol at blocking or hampering the trimerization of the SARS-CoV-2 spike glycoprotein, in addition to inhibiting virus-cell interactions, which supports the potential use of arbidol to treat COVID-19 (315).
T441 3593-3829 Sentence denotes Chen et al. (316) demonstrated that arbidol therapy was able to shorten the course of the disease and promote clinical improvement, resulting in low fever and improvements in dry cough without side effects faster than the control group.
T442 3830-3961 Sentence denotes Zhu et al. (317) also demonstrated the effects of arbidol by retrospectively analyzing the clinical data from 50 COVID-19 patients.
T443 3962-4336 Sentence denotes The study demonstrated that the use of arbidol monotherapy, without association with other drugs, was more effective than the treatment with lopinavir/ritonavir, showing clinical improvement of the disease, presenting a total elimination of viral load over a shorter duration; in addition, no fever or ARDS were reported compared with those in the lopinavir/ritonavir group.
T444 4337-4551 Sentence denotes Ribavirin is another antiviral drug used in association with lopinavir/ritonavir to treat SARS-CoV-1 and was able to reduce viral load, risk of adverse clinical outcomes, ARDS, or death in SARS patients (304, 318).
T445 4552-4779 Sentence denotes Ribavirin has a broad antiviral spectrum as it is a nucleotide analog that competes for the active site of RdRp, a crucial enzyme in the life cycle of RNA viruses, inhibiting viral replication and transcription (221, 319, 320).
T446 4780-4986 Sentence denotes Elfiky (320) conducted an in silico study demonstrating that ribavirin and other antivirals such as sofosbuvir can strongly bind to coronavirus RdRp, preventing the transcription of new copies of viral RNA.
T447 4987-5197 Sentence denotes Only a few clinical studies have investigated the effect of ribavirin on COVID-19 patients, with the studies available generally focusing on the association of ribavirin and other therapeutic schemes (321–323).
T448 5198-5295 Sentence denotes Nevertheless, China’s government (324) has recommended the use of ribavirin in COVID-19 patients.
T449 5296-5387 Sentence denotes Remdesivir (RDV) is also among the several potential drugs tested for SARS-CoV-2 treatment.
T450 5388-5562 Sentence denotes Originally developed to treat Ebola virus infection, RDV is active against RNA viruses from different families, including Coronaviridae (e.g., SARS-CoV-1 and MERS-CoV) (325).
T451 5563-5640 Sentence denotes RDV showed an in vitro effective antiviral activity against SARS-CoV-2 (326).
T452 5641-5866 Sentence denotes Grein et al. (327) conducted a cohort study with 53 COVID-19 patients treated with RDV and found that 68% of them had improved oxygen-support class, whereas 57% of the patients receiving mechanical ventilation were extubated.
T453 5867-6017 Sentence denotes Overall mortality reached 13% over a median follow-up of 18 days, however, viral load data were not collected to confirm the antiviral effects of RDV.
T454 6018-6244 Sentence denotes The biggest issue with this study is that the authors did not include a group without RDV, which hampers the performance of comparative statistical analyses to prove whether the data found resulted from the treatment with RDV.
T455 6245-6475 Sentence denotes Another double-blind, randomized, placebo-controlled trial of intravenous RDV conducted in adults hospitalized with COVID-19 with evidence of lower respiratory tract involvement was performed in different parts of the world (328).
T456 6476-6696 Sentence denotes The study of Beigel and colleagues (328) enrolled 1,063 COVID19 pneumonia patients, 538 of whom were assigned to the treatment with RDV and 521 to a placebo, showed the effectiveness of RDV in treating COVID-19 patients.
T457 6697-6909 Sentence denotes The drug was superior to the placebo in reducing the recovery time in hospitalized COVID-19 patients and decreased the mortality rate in the RDV group, however, this result did not reach statistical significance.
T458 6910-7168 Sentence denotes Antionori et al. (329), analyzing patients with severe COVID-19 pneumonia in an intensive care unit (ICU) who were treated for 10 days with RDV, found that on the 28th day, 38.9% showed improvement, 16.7% were still on mechanical ventilation, and 44.4% died.
T459 7169-7349 Sentence denotes The data suggest that this treatment can benefit hospitalized patients who are not in the ICU, where the clinical result was better and adverse events are observed less frequently.
T460 7350-7568 Sentence denotes Alternatively, the randomized, double-blind, placebo-controlled, multicenter trial with 273 ill individuals performed by Wang et al. revealed that RDV intravenous administration was well-tolerated in COVID-19 patients.
T461 7569-7660 Sentence denotes However, the authors did not find any clinical improvement or significant antiviral effect.
T462 7661-7872 Sentence denotes Goldman et al. (330), in another phase 3 clinical trial on 397 patients with severe COVID-19 without mechanical ventilation support, also did not find differences between 5-day and 10-day courses of RDV therapy.
T463 7873-8080 Sentence denotes The RDV data currently available are still controversial, however, dozens of clinical studies are currently using this drug as an alternative treatment for COVID-19, possibly further elucidating its effects.
T464 8081-8257 Sentence denotes The efficiency of favipiravir, another anti-influenza RdRp inhibitor, has also been clinically assessed and was approved for COVID-19 treatment in China, March 2020 (331, 332).
T465 8258-8384 Sentence denotes An experimental study carried out with the VERO cell line showed that the drug has in vitro activity against SARS-CoV-2 (326).
T466 8385-8701 Sentence denotes Aiming at comparing the effects of favipiravir and lopinavir/ritonavir, Cai et al. (333) conducted an open, non-randomized, before-after controlled study with 80 patients and found that favipiravir favored viral clearance and improved chest CT, having caused fewer adverse effects than the lopinavir/ritonavir group.
T467 8702-8770 Sentence denotes Currently, 31 clinical trials using this medication are in progress.
T468 8771-8979 Sentence denotes Regarding antivirals, type I IFN is a group of cytokines comprising the α and β subtypes, among others, with an important role in antiviral immunity that interferes with viral replication, as discussed above.
T469 8980-9267 Sentence denotes Many studies have shown the protective effect of type I IFN associated with antiviral therapies for patients with SARS and MERS [reviewed by Sallard et al. (334)], which arouses the interest of the scientific community in type I IFN as a potential treatment against SARS-CoV-2 (334–337).
T470 9268-9420 Sentence denotes Despite their efficacy against SARS-CoV-2 (338, 339), the results of in vitro studies using IFN-α and -β to treat COVID-19 patients remain inconclusive.
T471 9421-9632 Sentence denotes Such uncertain nature of the results is associated with biases present in these studies, which include limited-size sample, heterogeneous experimental designs/clinical status, and the type of IFN isoform tested.
T472 9633-9827 Sentence denotes In addition, since COVID-19 treatments rarely involve monotherapy, it is difficult to assess whether the results derived from the tested IFN or the drugs used in combination (322, 323, 340–343).
T473 9828-10084 Sentence denotes It is also worth mentioning that, as discussed above, type I IFN appears to exacerbate inflammation in the progression to severe COVID-19; the timing of administration and subgroups targeted for treatment with type I IFN need to be considered with caution.
T474 10085-10441 Sentence denotes A recent retrospective multicenter cohort study of 446 Chinese patients with COVID-19 reported that among severe to critical COVID-19 patients, early administration (≤5 days after admission) of IFN-α2b decreased mortality in comparison with no admission of IFN-α2b, whereas no significant benefit was associated with IFN-α2b use in moderately ill patients.
T475 10442-10558 Sentence denotes However, late use of IFN-α2b increased mortality and delayed recovery of severe to critical COVID-19 patients (344).
T476 10559-10784 Sentence denotes Zhou et al. (341), investigated the isolated effect of IFN-α in a cohort study comparing 77 patients with moderate COVID-19 treated with nebulized IFN-α2b (5 mU b.i.d.), oral arbidol (200 mg t.i.d.), or a combination of both.
T477 10785-11066 Sentence denotes Although the study did not include a control group, the treatment with IFN-α2b, either containing arbidol or not, significantly reduced the duration of detectable virus in the upper respiratory tract and the circulating of inflammatory markers (IL-6 and C-reactive protein levels).
T478 11067-11396 Sentence denotes Still, in a retrospective multicenter cohort study with 141 mild COVID-19 patients by Xu et al. (342), the arbidol/IFN-α2b combination proved more effective in accelerating pneumonia recovery than IFN-α2b monotherapy, but this was not the case for viral clearance or reducing the length of hospital stay than IFN-α2b monotherapy.
T479 11397-11738 Sentence denotes Hung et al. (322) assessed the effect of IFN-β on COVID-19 patients and found that the triple combination of IFN-β1b, lopinavir/ritonavir, and ribavirin was safer and more effective than lopinavir/ritonavir alone at alleviating symptoms, shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19.
T480 11739-11868 Sentence denotes Similarly, an open randomized clinical trial was carried out by Danoudi-Monfared et al. (345), analyzing treatment with IFN-β-1a.
T481 11869-12109 Sentence denotes The IFN group of COVID-19 patients (n=42) received IFN β-1a in addition to the protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir) while the control group (n=39) received only the protocol medications.
T482 12110-12237 Sentence denotes The IFN-β-1a-treated patients showed a significantly increased discharge rate on day 14 and decreased mortality within 28 days.
T483 12238-12346 Sentence denotes A better survival rate was also observed when patients received IFN- β-1a in the early stage of the disease.
T484 12347-12443 Sentence denotes The COVID-19 treatment guidelines of many countries already recommend the use of IFNs α/β (335).
T485 12444-12570 Sentence denotes Currently, all over the world, more than 20 clinical trials are using IFN-α and/or β alone or in association with other drugs.