Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study
Francesco Di Pierro, Giuseppe Derosa, Pamela Maffioli, Alexander Bertuccioli, Stefano Togni, Antonella Riva, Pietro Allegrini, Amjad Khan, Saeed Khan, Bilal Ahmad Khan, Naireen Altaf, Maria Zahid, Ikram Din Ujjan, Roohi Nigar, Mehwish Imam Khushk, Maryam Phulpoto, Amanullah Lail, Bikha Ram Devrajani, Sagheer Ahmed
International Journal of General Medicine, doi:10.2147/ijgm.s318720
Background: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility. Quercetin in a delivery-food grade system with sunflower phospholipids (Quercetin Phytosome ® , QP) increases its oral absorption up to 20-fold. Methods: In the present prospective, randomized, controlled, and open-label study, a daily dose of 1000 mg of QP was investigated for 30 days in 152 COVID-19 outpatients to disclose its adjuvant effect in treating the early symptoms and in preventing the severe outcomes of the disease.
Results: The results revealed a reduction in frequency and length of hospitalization, in need of non-invasive oxygen therapy, in progression to intensive care units and in number of deaths. The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties. Conclusion: QP is a safe agent and in combination with standard care, when used in early stage of viral infection, could aid in improving the early symptoms and help in preventing the severity of COVID-19 disease. It is suggested that a double-blind, placebo-controlled study should be urgently carried out to confirm the results of our study.
International Journal of General Medicine
Dovepress
DovePress International Journal of General Medicine 2021:14
References
Abian, Ortega-Alarcon, Jimenez-Alesanco, Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, Int J Biol Macromol,
doi:10.1016/j.ijbiomac.2020.07.235Almatroodi, Alsahli, Almatroudi, Potential therapeutic targets of quercetin, a plant flavonol, and its role in the therapy of various types of cancer through the modulation of various cell signaling pathways, Molecules,
doi:10.3390/molecules26051315Batiha, Beshbishy, Ikram, The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin, Foods,
doi:10.3390/foods9030374Brito, Lima, Cordeiro, Da, Nizer, Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: systematic review and meta-analysis of preclinical studies, Phytother Res,
doi:10.1002/ptr.7122David, Arulmoli, Parasuraman, Overviews of biological importance of quercetin: a bioactive flavonoid, Pharmacogn Rev,
doi:10.4103/0973-7847.194044Derosa, Maffioli, Angelo, Pierro, A role for quercetin in coronavirus disease 2019 (COVID-19), Phytother Res,
doi:10.1002/ptr.6887Gao, Liu, Wang, Liu, Xu et al., Preparation of a chemically stable quercetin formulation using nanosuspension technology, Int J Pharm,
doi:10.1016/j.ijpharm.2010.11.009Gautam, Madathil, Tahani, Medium-term outcome of severe to critically ill patients with SARS-CoV-2 infection, Clin Infect Dis,
doi:10.1093/cid/ciab341Heinz, Henson, Austin, Nieman, Quercetin supplementation and upper respiratory tract infection: a randomized community clinical trial, Pharmacol Res,
doi:10.1016/j.phrs.2010.05.001Karki, Verma, Trozzi, Tao, Kraka et al., Predicting Potential SARS-COV-2 drugs-in depth drug database screening using deep neural network framework SSnet, classical virtual screening and docking, Int J Mol Sci,
doi:10.3390/ijms22041573Khaerunnisa, Kurniawan, Awaluddin, Suhartati, Soetjipto, Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study,
doi:10.20944/preprints.202003.0226.v1Kim, Ryu, Social distancing attitudes, national context, and health outcomes during the COVID-19 pandemic: findings from a global survey, Prev Med,
doi:10.1016/j.ypmed.2021.106544Lindinger-Sternart, Kaur, Widyaningsih, Patel, COVID-19 phobia across the world: impact of resilience on COVID-19 phobia in different nations, Couns Psychother Res,
doi:10.1002/capr.12387Luo, Zhang, Luo, Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China, Chin Med,
doi:10.1186/s13020-020-00317-xMirtaleb, Mirtaleb, Nosrati, Heshmatnia, Falak et al., Potential therapeutic agents to COVID-19: an update review on antiviral therapy, immunotherapy, and cell therapy, Biomed Pharmacother,
doi:10.1016/j.biopha.2021.111518Nayak, Mishra, Naik, Swapnarekha, Cengiz et al., An impact study of COVID-19 on six different industries: automobile, energy and power, agriculture, education, travel and tourism and consumer electronics, Expert Syst,
doi:10.1111/exsy.12677Pandey, Rane, Chatterjee, Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in-silico study for drug development, J Biomol Struct Dyn,
doi:10.1080/07391102.2020.1796811Patel, Mistry, Shinde, Syed, Singh et al., Pro-inflammatory cytokine regulation of P-glycoprotein in the developing blood-brain barrier, Eur J Med Chem,
doi:10.1371/journal.pone.0043022Pawar, Pal, Molecular and functional resemblance of dexamethasone and quercetin: a paradigm worth exploring in dexamethasone-nonresponsive COVID-19 patients, Phytother Res,
doi:10.1002/ptr.6886Riva, Ronchi, Petrangolini, Bosisio, Allegrini, Improved oral absorption of quercetin from quercetin Phytosome ® , a new delivery system based on food grade lecithin, Eur J Drug Metab Pharmacokinet,
doi:10.1007/s13318-018-0517-3Smith, Smith, Repurposing therapeutics for COVID-19: supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface, ChemRxiv,
doi:10.26434/chemrxiv.11871402.v3Wang, Sun, Mao, The biological activities, chemical stability, metabolism, and delivery systems of quercetin: a review, Trends Food Sci Technol,
doi:10.1016/j.tifs.2016.07.004Williamson, Kerimi, Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike protein-angiotensin converting enzyme-2 (ACE2) interaction, Biochem Pharmacol,
doi:10.1016/j.bcp.2020.114123Zhang, Wu, Zhang, Deng, Peng, In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus, J Integr Med,
doi:10.1016/j.joim.2020.02.005{ 'indexed': {'date-parts': [[2024, 3, 29]], 'date-time': '2024-03-29T06:35:18Z', 'timestamp': 1711694118902},
'reference-count': 30,
'publisher': 'Informa UK Limited',
'license': [ { 'start': { 'date-parts': [[2021, 6, 1]],
'date-time': '2021-06-01T00:00:00Z',
'timestamp': 1622505600000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by-nc/3.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'DOI': '10.2147/ijgm.s318720',
'type': 'journal-article',
'created': {'date-parts': [[2021, 6, 8]], 'date-time': '2021-06-08T00:02:37Z', 'timestamp': 1623110557000},
'page': '2359-2366',
'source': 'Crossref',
'is-referenced-by-count': 108,
'title': 'Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 '
'Infection: A Prospective, Randomized, Controlled, and Open-Label Study',
'prefix': '10.2147',
'volume': 'Volume 14',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-6654-8675',
'authenticated-orcid': True,
'given': 'Francesco',
'family': 'Di Pierro',
'sequence': 'first',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-3573-4760',
'authenticated-orcid': True,
'given': 'Giuseppe',
'family': 'Derosa',
'sequence': 'additional',
'affiliation': []},
{'given': 'Pamela', 'family': 'Maffioli', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-3922-9115',
'authenticated-orcid': True,
'given': 'Alexander',
'family': 'Bertuccioli',
'sequence': 'additional',
'affiliation': []},
{'given': 'Stefano', 'family': 'Togni', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-2819-943X',
'authenticated-orcid': True,
'given': 'Antonella',
'family': 'Riva',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-4380-9577',
'authenticated-orcid': True,
'given': 'Pietro',
'family': 'Allegrini',
'sequence': 'additional',
'affiliation': []},
{'given': 'Amjad', 'family': 'Khan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Saeed', 'family': 'Khan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bilal Ahmad', 'family': 'Khan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Naireen', 'family': 'Altaf', 'sequence': 'additional', 'affiliation': []},
{'given': 'Maria', 'family': 'Zahid', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ikram Din', 'family': 'Ujjan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Roohi', 'family': 'Nigar', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mehwish Imam', 'family': 'Khushk', 'sequence': 'additional', 'affiliation': []},
{'given': 'Maryam', 'family': 'Phulpoto', 'sequence': 'additional', 'affiliation': []},
{'given': 'Amanullah', 'family': 'Lail', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bikha Ram', 'family': 'Devrajani', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sagheer', 'family': 'Ahmed', 'sequence': 'additional', 'affiliation': []}],
'member': '301',
'published-online': {'date-parts': [[2021, 6]]},
'reference': [ { 'key': 'ref1',
'doi-asserted-by': 'publisher',
'first-page': '106544',
'DOI': '10.1016/j.ypmed.2021.106544',
'volume': '148',
'author': 'Kim',
'year': '2021',
'journal-title': 'Prev Med'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'first-page': '290',
'DOI': '10.1002/capr.12387',
'volume': '21',
'author': 'Lindinger-Sternart',
'year': '2021',
'journal-title': 'Couns Psychother Res'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'author': 'Nayak',
'year': '2021',
'journal-title': 'Expert Syst',
'DOI': '10.1111/exsy.12677'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'first-page': '520',
'DOI': '10.1038/d41586-021-00728-2',
'volume': '591',
'author': 'Aschwanden',
'year': '2021',
'journal-title': 'Nature'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'first-page': '111518',
'DOI': '10.1016/j.biopha.2021.111518',
'volume': '138',
'author': 'Mirtaleb',
'year': '2021',
'journal-title': 'Biomed Pharmacother'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'first-page': '1573',
'DOI': '10.3390/ijms22041573',
'volume': '22',
'author': 'Karki',
'year': '2021',
'journal-title': 'Int J Mol Sci'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'first-page': '104859',
'DOI': '10.1016/j.phrs.2020.104859',
'volume': '157',
'author': 'McKee',
'year': '2020',
'journal-title': 'Pharmacol Res'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'first-page': '152',
'DOI': '10.1016/j.joim.2020.02.005',
'volume': '18',
'author': 'Zhang',
'year': '2020',
'journal-title': 'J Integr Med'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'author': 'Smith',
'year': '2020',
'journal-title': 'ChemRxiv',
'DOI': '10.26434/chemrxiv.11871402.v3'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'first-page': '114123',
'DOI': '10.1016/j.bcp.2020.114123',
'volume': '178',
'author': 'Williamson',
'year': '2020',
'journal-title': 'Biochem Pharmacol'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1080/07391102.2020.1796811',
'author': 'Pandey',
'year': '2020',
'journal-title': 'J Biomol Struct Dyn'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'author': 'Khaerunnisa',
'year': '2020',
'journal-title': 'Preprints',
'DOI': '10.20944/preprints.202003.0226.v1'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'first-page': '1693',
'DOI': '10.1016/j.ijbiomac.2020.07.235',
'volume': '164',
'author': 'Abian',
'year': '2020',
'journal-title': 'Int J Biol Macromol'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'first-page': '84',
'DOI': '10.4103/0973-7847.194044',
'volume': '10',
'author': 'Anand David',
'year': '2016',
'journal-title': 'Pharmacogn Rev'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': '231',
'DOI': '10.1016/j.ijpharm.2010.11.009',
'volume': '404',
'author': 'Gao',
'year': '2011',
'journal-title': 'Int J Pharm'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'first-page': '21',
'DOI': '10.1016/j.tifs.2016.07.004',
'volume': '56',
'author': 'Wang',
'year': '2016',
'journal-title': 'Trends Food Sci Technol'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'first-page': '169',
'DOI': '10.1007/s13318-018-0517-3',
'volume': '44',
'author': 'Riva',
'year': '2019',
'journal-title': 'Eur J Drug Metab Pharmacokinet'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'first-page': '1230',
'DOI': '10.1002/ptr.6887',
'volume': '35',
'author': 'Derosa',
'year': '2021',
'journal-title': 'Phytother Res'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'author': 'Di Pierro',
'year': '2020',
'journal-title': 'Minerva Gastroenterol Dietol',
'DOI': '10.23736/S1121-421X.20.02771-3'},
{ 'key': 'ref20',
'doi-asserted-by': 'publisher',
'first-page': '374',
'DOI': '10.3390/foods9030374',
'volume': '9',
'author': 'Batiha',
'year': '2020',
'journal-title': 'Foods'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'author': 'Gautam',
'year': '2021',
'journal-title': 'Clin Infect Dis',
'DOI': '10.1093/cid/ciab341'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'first-page': '1315',
'DOI': '10.3390/molecules26051315',
'volume': '26',
'author': 'Almatroodi',
'year': '2021',
'journal-title': 'Molecules'},
{ 'key': 'ref23',
'doi-asserted-by': 'publisher',
'first-page': '889',
'DOI': '10.1016/j.ejmech.2018.06.053',
'volume': '155',
'author': 'Patel',
'year': '2018',
'journal-title': 'Eur J Med Chem'},
{ 'key': 'ref24',
'doi-asserted-by': 'publisher',
'first-page': 'e43022',
'DOI': '10.1371/journal.pone.0043022',
'volume': '7',
'author': 'Iqbal',
'year': '2012',
'journal-title': 'PLoS One'},
{ 'key': 'ref25',
'doi-asserted-by': 'publisher',
'first-page': '3085',
'DOI': '10.1002/ptr.6886',
'volume': '34',
'author': 'Pawar',
'year': '2020',
'journal-title': 'Phytother Res'},
{ 'key': 'ref26',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1007/s12011-020-02437-9',
'author': 'Pal',
'year': '2020',
'journal-title': 'Biol Trace Elem Res'},
{ 'key': 'ref27',
'doi-asserted-by': 'publisher',
'first-page': '1123',
'DOI': '10.3390/molecules24061123',
'volume': '24',
'author': 'Xu',
'year': '2019',
'journal-title': 'Molecules'},
{ 'key': 'ref28',
'doi-asserted-by': 'publisher',
'first-page': '237',
'DOI': '10.1016/j.phrs.2010.05.001',
'volume': '62',
'author': 'Heinz',
'year': '2010',
'journal-title': 'Pharmacol Res'},
{ 'key': 'ref29',
'doi-asserted-by': 'publisher',
'first-page': '34',
'DOI': '10.1186/s13020-020-00317-x',
'volume': '15',
'author': 'Luo',
'year': '2020',
'journal-title': 'Chin Med'},
{ 'key': 'ref30',
'doi-asserted-by': 'publisher',
'author': 'Brito',
'year': '2021',
'journal-title': 'Phytother Res',
'DOI': '10.1002/ptr.7122'}],
'container-title': 'International Journal of General Medicine',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.dovepress.com/getfile.php?fileID=70294',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.dovepress.com/getfile.php?fileID=70294',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 6, 8]],
'date-time': '2021-06-08T00:02:39Z',
'timestamp': 1623110559000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://www.dovepress.com/possible-therapeutic-effects-of-adjuvant-quercetin-supplementation-aga-peer-reviewed-fulltext-article-IJGM'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 6]]},
'references-count': 30,
'URL': 'http://dx.doi.org/10.2147/IJGM.S318720',
'relation': {},
'ISSN': ['1178-7074'],
'subject': ['General Medicine'],
'container-title-short': 'IJGM',
'published': {'date-parts': [[2021, 6]]}}
