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PMC:7319919 JSONTXT 17 Projects

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Id Subject Object Predicate Lexical cue
T1 0-22 Sentence denotes Imatinib for COVID-19:
T2 23-36 Sentence denotes A case report
T3 38-329 Sentence denotes Since first cases of pneumonia of unknown etiology were reported on December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health issue and its related disease (COVID-19) was finally declared a pandemic by World Health Organization on March 2020 [1].
T4 330-511 Sentence denotes To date, there is no evidence that consistently supports any treatment for COVID-19 patients, so identifying new therapeutic options seems crucial in the management of this disease.
T5 512-685 Sentence denotes Imatinib is a tyrosine kinase inhibitor with a well-known anti-tumor activity against several cancers including chronic myeloid leukemia and gastrointestinal stromal tumors.
T6 686-862 Sentence denotes According to previously published data, this drug has also shown antiviral, immunomodulatory and endothelium-protective properties which may be potentially helpful in COVID-19.
T7 863-958 Sentence denotes In fact, imatinib has been pointed out as an unexplored treatment for SARS-CoV-2 infection [2].
T8 959-1150 Sentence denotes We report the case of a patient with COVID-19 pneumonia who received imatinib due to clinical deterioration despite dual therapy with hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r).
T9 1151-1288 Sentence denotes On March 12, a 38-year-old woman was admitted to our department with a 6-day history of fever up to 39 °C, arthralgia, malaise and cough.
T10 1289-1357 Sentence denotes Her blood pressure, heart rate and respiratory rate were all normal.
T11 1358-1452 Sentence denotes Her temperature was 37.1 °C and oxygen saturation was 96% while she was breathing ambient air.
T12 1453-1527 Sentence denotes Physical examination only revealed minimal wheezing on chest auscultation.
T13 1528-1680 Sentence denotes Laboratory results showed a mild elevation of C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels, and a normal lymphocyte count (Table 1 ).
T14 1681-1723 Sentence denotes Chest X-ray confirmed bilateral pneumonia.
T15 1724-1936 Sentence denotes Polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, so treatment with HCQ and LPV/r, as well as empiric therapy with ceftriaxone, was initiated in accordance with hospital protocol.
T16 1937-1966 Sentence denotes Table 1 - Laboratory results.
T17 1967-2164 Sentence denotes Variable Day 6 of symptoms Day 10 of symptoms Day 13 of symptoms(day 2 of imatinib) Day 14 of symptoms(day 3 of imatinib) Day 16 of symptoms(day 5 of imatinib and discharge) 20 days after discharge
T18 2165-2209 Sentence denotes CRP, mg/dL 4.79⁎ 21.00⁎ – 25.04⁎ 7.52⁎ 0.57⁎
T19 2210-2256 Sentence denotes Procalcitonin, ng/mL – 0.1 0.09 0.06 0.05 0.01
T20 2257-2295 Sentence denotes LDH, IU/L 338⁎ 532⁎ 318⁎ 306⁎ 326⁎ 222
T21 2296-2346 Sentence denotes Venous lactate, mmol/L 1.0 3.2⁎ 2.7⁎ 2.5⁎ 1.6⁎ 1.1
T22 2347-2404 Sentence denotes White-cell count, × 109/L 7.09 8.48 10.19 9.67 7.61 10.25
T23 2405-2462 Sentence denotes Neutrophil count, × 109/L 5.44 6.76 8.29⁎ 7.92⁎ 5.56 6.07
T24 2463-2519 Sentence denotes Lymphocyte count, × 109/L 1.17 1.31 1.09 0.84† 1.35 3.14
T25 2520-2558 Sentence denotes D-dimer, ng/mL – 580⁎ 760⁎ 1129⁎ – 449
T26 2559-2613 Sentence denotes CRP = C-reactive protein; LDH = Lactate dehydrogenase.
T27 2614-2656 Sentence denotes ⁎ The value was above the reference range.
T28 2657-2699 Sentence denotes † The value was below the reference range.
T29 2700-2880 Sentence denotes The patient reported initial improvement; however, on March 15 (day 9 of symptoms) fever recurred and supplemental oxygen by nasal cannula at a rate of 3 l per minute was required.
T30 2881-2993 Sentence denotes Furthermore, both an increase in CRP levels (Table 1) and radiological deterioration were observed (Fig. 1 , a).
T31 2994-3386 Sentence denotes These clinical changes suggested that the disease was progressing to an early phase of a hyperinflammatory state despite treatment with HCQ and LPV/r; thus, after assessing the safety profile of imatinib [3] and reviewing previous publications about its antiviral and immunomodulatory properties, we considered that this drug may have potentially beneficial effects in such clinical scenario.
T32 3387-3586 Sentence denotes Hence, informed consent was obtained and imatinib (400 mg once daily) was added on day 12 of symptoms, while ceftriaxone was interrupted since there was no evidence of concurrent bacterial infection.
T33 3587-3728 Sentence denotes Three days later the fever disappeared, supplemental oxygen was discontinued and radiological stability of pulmonary opacities was confirmed.
T34 3729-3940 Sentence denotes Moreover, improvement in laboratory parameters was observed on day 5 of imatinib so it was stopped and the patient was subsequently discharged on day 16 of symptoms after also completing 9 days of HCQ and LPV/r.
T35 3941-4108 Sentence denotes She remained asymptomatic on April 11 (20 days after discharge), her blood tests were then normal (Table 1) and pulmonary opacities had almost disappeared (Fig. 1, b).
T36 4109-4382 Sentence denotes Fig. 1 a Portable chest X-ray showing radiological deterioration with bilateral patchy opacities (March 17, day 11 of symptoms). b Marked improvement of opacities in posteroanterior chest radiograph (April 11, day 20 after discharge and day 36 after the onset of symptoms).
T37 4383-4716 Sentence denotes Although developed targeting the oncogenic fusion protein BCR-ABL, imatinib is able to inhibit other tyrosine kinases such as c-KIT, platelet-derived growth factor receptor and Abelson kinases (ABL) type 1 and 2 [4]; therefore, it has been postulated that the biological activity of this drug is not restricted to anticancer effects.
T38 4717-4792 Sentence denotes In this regard, immunomodulatory properties of imatinib have been reported.
T39 4793-5119 Sentence denotes Murine models of sepsis and acute lung injury have suggested a protective role of this drug by reducing pulmonary edema, preventing histological damage and improving endothelial barrier dysfunction, probably through attenuation of proinflammatory cytokine release including interleukin-6 and tumor necrosis factor-alpha [4,5].
T40 5120-5329 Sentence denotes These effects over inflammatory activation might be mediated by the inhibition of transcription factor NF-κB according to previous evidence from both animal models and studies with human cells [[4], [5], [6]].
T41 5330-5483 Sentence denotes Since NF-κB represents a key element in several inflammatory pathways [7], imatinib could be helpful to modulate host immune response against SARS-CoV-2.
T42 5484-5591 Sentence denotes This is particularly noteworthy given that hyperinflammation plays a central role in severe COVID-19 [3,8].
T43 5592-5804 Sentence denotes In addition, imatinib has shown in vitro antiviral activity against severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses [9], which are phylogenetically related to SARS-CoV-2 [10].
T44 5805-5960 Sentence denotes In this sense, ABL2 appears to be involved in the virus-cell fusion process, so its blockage could modulate the entry of coronaviruses into host cells [9].
T45 5961-6155 Sentence denotes These data also suggest that imatinib might be useful in early stages of SARS-CoV-2 infection, although further research is needed to ascertain the antiviral properties of this drug in COVID-19.
T46 6156-6265 Sentence denotes To our knowledge, this is the first reported case of SARS-CoV-2 infection successfully treated with imatinib.
T47 6266-6500 Sentence denotes However, elucidating the relevance of any therapeutic intervention from a single case report is always controversial since clinical outcomes may be influenced by some confounding factors such as the concomitant use of other therapies.
T48 6501-6646 Sentence denotes Nevertheless, taking into account all the above mentioned data, we believe that imatinib should be considered a potential treatment for COVID-19.
T49 6648-6655 Sentence denotes Funding
T50 6656-6689 Sentence denotes No external funding was received.
T51 6691-6724 Sentence denotes Declaration of Competing Interest
T52 6725-6912 Sentence denotes David Bernal-Bello is the principal investigator of a non-sponsored randomized trial assessing the therapeutic role of lopinavir/ritonavir, imatinib, and baricitinib in COVID-19 patients.
T53 6913-6975 Sentence denotes The rest of the authors are sub-investigators in this project.
T54 6976-7025 Sentence denotes All authors declare no other competing interests.