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      Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial

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          Abstract

          Background

          The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing global pandemic known as COVID-19. Based on the potential antiviral role of quercetin, and on its described anti-blood clotting, anti-inflammatory and antioxidant properties, we hypothesize that subjects with mild COVID-19 treated with Quercetin Phytosome ® (QP), a novel bioavailable form of quercetin, may have a shorter time to virus clearance, a milder symptomatology, and higher probabilities of a benign earlier resolution of the disease.

          Methods

          In our 2-week, randomized, open-label, and controlled clinical study, we have enrolled 42 COVID-19 outpatients. Twenty-one have been treated with the standard of care (SC), and 21 with QP as add-on supplementation to the SC. Our main aims were to check virus clearance and symptoms.

          Results

          The interim results reveal that after 1 week of treatment, 16 patients of the QP group were tested negative for SARS-CoV-2 and 12 patients had all their symptoms diminished; in the SC group, 2 patients were tested SARS-CoV-2 negative and 4 patients had their symptoms partially improved. By 2 weeks, the remaining 5 patients of the QP group tested negative for SARS-CoV-2, whereas in the SC group out of 19 remaining patients, 17 tested negatives by week 2, one tested negative by week 3 and one patient, still positive, expired by day 20. Concerning blood parameters, the add on therapy with QP, reduced LDH (−35.5%), Ferritin (−40%), CRP (−54.8%) and D-dimer (−11.9%).

          Conclusion

          QP statistically shortens the timing of molecular test conversion from positive to negative, reducing at the same time symptoms severity and negative predictors of COVID-19.

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          Most cited references36

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          The cytokine storm and COVID‐19

          Abstract Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of May 11, 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. This article is protected by copyright. All rights reserved.
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            Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy

            A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24–72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0–2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.
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              Quercetin, Inflammation and Immunity

              In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                24 June 2021
                2021
                : 14
                : 2807-2816
                Affiliations
                [1 ]Scientific & Research Department, Velleja Research , Milan, Italy
                [2 ]Digestive Endoscopy, Fondazione Poliambulanza , Brescia, Italy
                [3 ]Department of Medicine, King Edward Medical University , Lahore, Pakistan
                [4 ]Chemistry Research Laboratory, Department of Chemistry, University of Oxford , Oxford, UK
                [5 ]University of Health Sciences , Lahore, Pakistan
                [6 ]Department of Biomolecular Sciences (DISB), University of Urbino , Urbino, Italy
                [7 ]Department of Internal Medicine and Therapeutics, University of Pavia , Pavia, Italy
                [8 ]Laboratory of Molecular Medicine, University of Pavia , Pavia, Italy
                [9 ]Indena Research Department , Milan, Italy
                [10 ]Department of Molecular Pathology, Dow University of Health Sciences , Karachi, Pakistan
                Author notes
                Correspondence: Francesco Di Pierro Scientific & Research Department, Velleja Research , Milan, ItalyTel +39 0223510848Fax +39 0223 511894 Email f.dipierro@vellejaresearch.com
                Author information
                http://orcid.org/0000-0001-6654-8675
                http://orcid.org/0000-0002-3922-9115
                http://orcid.org/0000-0003-3573-4760
                http://orcid.org/0000-0003-2819-943X
                http://orcid.org/0000-0002-4380-9577
                Article
                318949
                10.2147/IJGM.S318949
                8238537
                34194240
                988849d4-fba2-4723-abee-ee8c45a30e8e
                © 2021 Di Pierro et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 06 May 2021
                : 11 June 2021
                Page count
                Figures: 2, Tables: 6, References: 36, Pages: 10
                Categories
                Clinical Trial Report

                Medicine
                sars-cov-2,rt-pcr,ldh,ferritin,crp,d-dimer,coronavirus,phytosome®
                Medicine
                sars-cov-2, rt-pcr, ldh, ferritin, crp, d-dimer, coronavirus, phytosome®

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