The effect of quercetin supplementation on clinical outcomes in COVID‐19 patients: A systematic review and meta‐analysis
Somayeh Ziaei, Malek Alimohammadi‐kamalabadi, Motahareh Hasani, Mahsa Malekahmadi, Emma Persad, Javad Heshmati
Food Science & Nutrition, doi:10.1002/fsn3.3715
COVID-19 is an extremely contagious respiratory disease that is caused by a newly identified type of coronavirus, known as SARS- CoV-2 (Sullivan et al., 2020). The disease was first identified in Wuhan, China, in December 2019, and quickly spread to become a global pandemic (Pollard et al., 2020) . To date, COVID-19 has infected millions of people worldwide, resulting in a significant number of deaths (Noor et al., 2020) . According to the WHO's website on March 7, 2023, there have been 759,408,703 confirmed cases of COVID-19 and 6,866,434 confirmed deaths directly or due to consequences of this pandemic infection (Melnyk et al., 2023) . COVID-19 can cause mild symptoms, such as coughing, diarrhea, high fever, muscle pain, fatigue, and a significant decrease in the sense of smell (Nehme et al., 2021) . However, if left untreated, it can lead to serious health complications. These may include acute respiratory distress
ACK N OWLED G M ENTS None.
FU N D I N G I N FO R M ATI O N None.
CO N FLI C T O F I NTE R E S T S TATE M E NT The authors have no competing interests to declare.
S U PP O RTI N G I N FO R M ATI O N Additional supporting information can be found online in the Supporting Information section at the end of this article.
References
Anand, Ziebuhr, Wadhwani, Mesters, Hilgenfeld, Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs, Science
Banchini, Cattaneo, Capelli, Serum ferritin levels in inflammation: A retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients, World Journal of Emergency Surgery
Bartziokas, Kostikas, Lactate dehydrogenase, COVID-19 and mortality, Medicina Clínica
Bhowmik, Nandi, Prakash, Kumar, Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis, Heliyon
Chaabi, Antiviral effects of quercetin and related compounds, Naturopathic Currents
Cheema, Sohail, Fatima, Shahid, Shahzil et al., Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis, Reviews in Medical Virology
Cirulli, Schiabor Barrett, Riffle, Bolze, Neveux et al., Long-term COVID-19 symptoms in a large unselected population
Darif, Hammi, Kihel, Saik, Guessous et al., The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?, Microbial Pathogenesis
De Lucena, Da Silva Santos, De Lima, De Albuquerque Borborema, De Azevêdo et al., Mechanism of inflammatory response in associated comorbidities in COVID-19, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
Di Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible therapeutic effects of adjuvant quercetin supplementation against early-stage covid-19 infection: A prospective, randomized, controlled, and open-label study, International Journal of General Medicine
Di Pierro, Iqtadar, Khan, Ullah Mumtaz, Masud Chaudhry et al., Potential clinical benefits of quercetin in the early stage of COVID-19: Results of a second, pilot, randomized, controlled and open-label clinical trial, International Journal of General Medicine
Di Pierro, Khan, Iqtadar, Mumtaz, Chaudhry et al., Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial, Frontiers in Pharmacology
Ehrlich, Uhl, Ioannidis, Hofree, Tenoever et al., The SARS-CoV-2 transcriptional metabolic signature in lung epithelium
Faghih Dinevari, Somi, Sadeghi Majd, Abbasalizad Farhangi, Nikniaz, Anemia predicts poor outcomes of COVID-19 in hospitalized patients: A prospective study in Iran, BMC Infectious Diseases
Fara, Mitrev, Rosalia, Assas, Cytokine storm and COVID-19: A chronicle of pro-inflammatory cytokines, Open Biology
Fialek, Pruc, Smereka, Jas, Rahnama-Hezavah et al., Diagnostic value of lactate dehydrogenase in COVID-19: A systematic review and meta-analysis, Cardiology Journal
Gasmi, Mujawdiya, Lysiuk, Shanaida, Peana et al., Quercetin in the prevention and treatment of coronavirus infections: A focus on SARS-CoV-2, Pharmaceuticals
Gollapalli, Rimac, Patil, Nalilu, Kandagalla et al., Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain-human angiotensinconverting enzyme 2 interface to combat SARS-CoV-2, Journal of Biomolecular Structure and Dynamics
Gonzalez-Rubio, Navarro-Lopez, Lopez-Najera, Lopez-Najera, Jimenez-Diaz et al., Cytokine release syndrome (CRS) and nicotine in COVID-19 patients: Trying to calm the storm, Frontiers in Immunology
Gowdy, Fessler, Emerging roles for cholesterol and lipoproteins in lung disease, Pulmonary Pharmacology & Therapeutics
Granado-Serrano, Martín, Bravo, Goya, Ramos, Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38, Chemico-Biological Interactions
Heidari, Mohammadi, Fathi, Cigary, Alisamir et al., Association of vitamin D status with COVID-19 disease severity in pediatric patients: A retrospective observational study, Health Science Reports
Heidary, Varnaseri, Gharebaghi, The potential use of persian herbal medicines against COVID-19 through angiotensinconverting enzyme 2, Archives of Clinical Infectious Diseases
Henry, Aggarwal, Wong, Benoit, Vikse et al., Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis, The American Journal of Emergency Medicine
Hirano, Murakami, COVID-19: A new virus, but a familiar receptor and cytokine release syndrome, Immunity
Huang, Pranata, Lim, Oehadian, Alisjahbana, C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: A meta-analysis, Therapeutic Advances in Respiratory Disease
Imran, Thabet, Alaqel, Alzahrani, Abida et al., The therapeutic and prophylactic potential of quercetin against COVID-19: An outlook on the clinical studies, inventive compositions, and patent literature, Antioxidants
Jo, Kim, Kim, Shin, Kim, Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors, Chemical Biology & Drug Design
Kadkhoda, COVID-19: An immunopathological view, MSphere
Kim, Jeong, Cho, Park, Park, Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway, Molecular Medicine Reports
Kressler, Millard-Stafford, Warren, Quercetin and endurance exercise capacity: A systematic review and metaanalysis, Medicine & Science in Sports & Exercise
Kuppusamy, Wankhar, Gurugubelli, Mahadevappa, Lepcha et al., Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes, Respiratory Physiology & Neurobiology
Lekić, Canová, Hořínek, Farghali, The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a hepatoprotective action of quercetin in lipopolysaccharide-induced hepatotoxicity of D-galactosamine sensitized rats, Fitoterapia
Li, Chen, Yang, Qiao, Zhang, Quercetin improves cognitive disorder in aging mice by inhibiting NLRP3 inflammasome activation, Food & Function
Lättig, Böhl, Fischer, Tischer, Tietböhl et al., Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: Rationale for lead design, Journal of Computer-Aided Molecular Design
Manjunath, Thimmulappa, Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19, Journal of Pharmaceutical Analysis
Melnyk, Kozarov, Wachsmann-Hogiu, A deconvolution approach to modelling surges in COVID-19 cases and deaths, Scientific Reports
Memon, Qureshi, Memon, Assessing the role of quarantine and isolation as control strategies for COVID-19 outbreak: A case study, Chaos, Solitons & Fractals
Moher, Liberati, Tetzlaff, Altman, Group, Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement, Annals of Internal Medicine
Moore, June, Cytokine release syndrome in severe COVID-19, Science
Morato, Bastos, Cajueiro, Normey-Rico, An optimal predictive control strategy for COVID-19 (SARS-CoV-2) social distancing policies in Brazil, Annual Reviews in Control
Morjaria, Nawar, Papanicolaou, Predmore, Kamboj, Determinants of COVID-19 disease severity in patients with cancer, Nature Medicine
Naymagon, Zubizarreta, Feld, Van Gerwen, Alsen et al., Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19, Thrombosis Research
Nehme, Braillard, Alcoba, Aebischer Perone, Courvoisier et al., COVID-19 symptoms: Longitudinal evolution and persistence in outpatient settings, Annals of Internal Medicine
Nguyen, Woo, Kang, Nguyen, Kim et al., Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris, Biotechnology Letters
Noor, Maqbool, Bhatti, Khan, Epidemiology of CoViD-19 pandemic: Recovery and mortality ratio around the globe, Pakistan Journal of Medical Sciences
Okamoto, Safety of quercetin for clinical application, International Journal of Molecular Medicine
Onal, Arslan, Ergun, Topuz, Semerci et al., Treatment of COVID-19 patients with quercetin: A prospective, single-Centre, randomized, controlled trial, Authorea Preprints
Ostadmohammadi, Milajerdi, Ayati, Kolahdooz, Asemi, Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials, Phytotherapy Research
Pawar, Pal, Goswami, Squitti, Rongiolettie, Molecular basis of quercetin as a plausible common denominator of macrophage-cholesterol-fenofibrate dependent potential COVID-19 treatment axis, Results in Chemistry
Pawar, Pal, Molecular and functional resemblance of dexamethasone and quercetin: A paradigm worth exploring in dexamethasone-nonresponsive COVID-19 patients, Phytotherapy Research
Pawar, Russo, Rani, Goswami, Russo et al., A critical evaluation of risk to reward ratio of quercetin supplementation for COVID-19 and associated comorbid conditions, Phytotherapy Research
Poggiali, Zaino, Immovilli, Rovero, Losi et al., Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients, Clinica Chimica Acta
Pollard, Morran, Nestor-Kalinoski, The COVID-19 pandemic: A global health crisis, Physiological Genomics
Reeves, Cochrane handbook for systematic reviews of interventions
Robilotti, Babady, Mead, Rolling, Perez-Johnston et al., None
Roe, Junod, Young, Beachboard, Stobart, Targeting novel structural and functional features of coronavirus protease nsp5 (3CLpro, Mpro) in the age of COVID-19, The Journal of General Virology
Rogerio, Dora, Andrade, Chaves, Silva et al., Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice, Pharmacological Research
Rostami, Mansouritorghabeh, D-dimer level in COVID-19 infection: A systematic review, Expert Review of Hematology
S Abian, Ortega-Alarcon, Jimenez-Alesanco, Ceballos-Laita, Vega et al., Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, International Journal of Biological Macromolecules
Sahebkar, Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials, Critical Reviews in Food Science and Nutrition
Santos, Morales, Álvarez, Castro, Robles et al., Determinants of COVID-19 disease severity in patients with underlying rheumatic disease, Clinical Rheumatology
Seeßle, Waterboer, Hippchen, Simon, Kirchner et al., Persistent symptoms in adult patients 1 year after coronavirus disease 2019 (COVID-19): A prospective cohort study, Clinical Infectious Diseases
Serban, Sahebkar, Zanchetti, Mikhailidis, Howard et al., Effects of quercetin on blood pressure: A systematic review and meta-analysis of randomized controlled trials, Journal of the American Heart Association
Shohan, Nashibi, Mahmoudian-Sani, Abolnezhadian, Ghafourian et al., The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial, European Journal of Pharmacology
Sullivan, Carlson, Cheng, Chilver, Dwyer et al., Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, march to September 2020, Eurosurveillance
Sun, Li, Li, Shangguan, Jiang et al., Quercetin as an antiviral agent inhibits the pseudorabies virus in vitro and in vivo, Virus Research
Szarpak, Ruetzler, Safiejko, Hampel, Pruc et al., Lactate dehydrogenase level as a COVID-19 severity marker, The American Journal of Emergency Medicine
Valle, Kim-Schulze, Huang, Beckmann, Nirenberg et al., An inflammatory cytokine signature predicts COVID-19 severity and survival, Nature Medicine
Valério, Georgetti, Magro, Casagrande, Cunha et al., Quercetin reduces inflammatory pain: Inhibition of oxidative stress and cytokine production, Journal of Natural Products
Vargas-Vargas, Cortés-Rojo, Ferritin levels and COVID-19, Revista Panamericana de Salud Pública
Wagner, Fachinetto, Dalla Corte, Brito, Severo et al., Quercitrin, a glycoside form of quercetin, prevents lipid peroxidation in vitro, Brain Research
Wang, C-reactive protein levels in the early stage of COVID-19, Médecine et Maladies Infectieuses
Wong, He, Siragam, Bi, Mbikay et al., Antiviral activity of quercetin-3-β-OD-glucoside against zika virus infection, Virologica Sinica
Xiong, Wang, Su, Cho, Xing, Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis, Pharmacological Research
Yan, Chu, Yang, Sze, Lai et al., Characterization of the lipidomic profile of human coronavirus-infected cells: Implications for lipid metabolism remodeling upon coronavirus replication, Viruses
Zhang, Xie, Gao, Pu, Wei et al., Quercetin regulates hepatic cholesterol metabolism by promoting cholesterolto-bile acid conversion and cholesterol efflux in rats, Nutrition Research
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Zupanets, Holubovska, Tarasenko, Bezuhla, Pasichnyk et al., Quercetin effectiveness in patients with COVID-19 associated pneumonia, Zaporizhzhia Medical Journal
