Neglected Effective Early Therapies against COVID-19: Focus on Functional Foods and Related Active Substances. A Review
Alberto Donzelli
doi:10.20944/preprints202312.1178.v1
The official recommendations for COVID-19 management in the outpatient setting focus on high-cost drugs, that show several problems and limitations. Therefore, other treatments may be considered, if they meet the following criteria: promising effectiveness, based on favorable randomized controlled trials (RCTs) of acceptable validity, provided the treatments are also: safe, convenient, biologically plausible, accessible and coming from researchers with no major conflict of interests. The focus is on some functional foods and their active ingredients, with further mention of a few other substances of different origin but meeting the above criteria. The supporting scientific evidence privileges meta-analyses of RCTs, the most valid study design, including the most solid outcome: all-cause mortality.
Conflicts of Interest: The Author declares no conflict of interest.
References
Abbaspour-Aghdam, Hazrati, Abdolmohammadi-Vahid, Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function, European Journal of Pharmacology,
doi:10.1016/j.ejphar.2022.175267
Abdelazeem, Ahmed, Awad, Elbadawy, Manasrah et al., The effects of curcumin as dietary supplement for patients with COVID-19: A systematic review of randomized clinical trials, Drug Discoveries & Therapeutics,
doi:10.5582/ddt.2022.01017
Abolhassani, Delavari, Landegren, Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19, J Allergy Clin Immunol,
doi:10.1016/j.jaci.2022.09.005.161
Ahmadi, Mehrabi, Zare, Efficacy of Nanocurcumin as an Add-On Treatment for Patients Hospitalized with COVID-19: A Double-Blind, Randomized Clinical Trial, International Journal of Clinical Practice,
doi:10.1155/2023/5734675
Ahmadi, Salari, Sharifi, Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial, Food Science and Nutrition,
doi:10.1002/fsn3.2226
Al-Haidari, Faiq, Ghareeb, Clinical Trial of Black Seeds Against COVID -19 in Kirkuk City / Iraq, Indian Journal of Forensic Medicine & Toxicology
Alizadeh, Keyhanian, Ghaderkhani, A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement, Iranian Journal of Allergy, Asthma and Immunology
Ameri, Frouz Asadi, Ziaei, Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial, Inflammopharmacology,
doi:10.1007/s10787-022-01096-7
Anand, Kunnumakkara, Newman, Aggarwal, Bioavailability of curcumin: Problems and promises, Mol. Pharm
Anderson, Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease, Infect. Dis. Ther
Arbel, Wolff Sagy, Hoshen, Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge, New Engl J Med,
doi:10.1056/NEJMoa2204919
Arefin, Rumi, Uddin, Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial, Indian Journal of Otolaryngology and Head & Neck Surgery,
doi:10.1007/s12070-021-02616-7
Arslan, Ergun, Topuz, Synergistic Effect of Quercetin and Vitamin C Against COVID-19: Is a Possible Guard for Front Liners, SSRN,
doi:10.2139/ssrn.3682517
Asadirad, Nashibi, Khodadadi, Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebocontrolled clinical trial, Phytotherapy Research,
doi:10.1002/ptr.7375
Ashraf, Ashraf, Ashraf, Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multi-center placebo-controlled randomized clinical trial, Phytotherapy Research,
doi:10.1002/ptr.7640
Askari, Sahebkar, Soleimani, The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized doubleblind, placebo-controlled trial, Trials,
doi:10.1186/s13063-022-06375-w
Ausina-Marquez, Ferrer, Oral antiseptics against coronavirus: Invitro and clinical evidence, J. Hosp. Infect
Bahrampour Juybari, Pourhanifeh, Hosseinzadeh, Hemati, Mehrzadi, Melatonin potentials against viral infections including COVID-19: Current evidence and new findings, Virus Res
Baker, Lugo-Candelas, Wu, Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity, JAMA Pediatr,
doi:10.1001/jamapediatrics.2020.3080
Baldia, Wernly, Flaatten, The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial, BMC Geriatr,
doi:10.1186/s12877-022-03709-w.162
Batiha, Beshbishy, Ikram, The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: Quercetin, Foods,
doi:10.3390/foods9030374
Baxter, Schwartz, Johnson, Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients, Ear, Nose & Throat Journal,
doi:10.1177/01455613221123737
Baxter, Schwartz, Johnson, Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients, Ear, Nose & Throat Journal,
doi:10.1177/01455613221123737
Bencheqroun, Ahmed, Kocak, A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2, Pathogens,
doi:10.3390/pathogens11050551
Bhaskar, Kumar, Krishnan, Antony, Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits, Nutrition,
doi:10.1016/j.nut.2012.01.019
Bologna, Madonna, Pone, Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study, Journal of Clinical Medicine,
doi:10.3390/jcm10245857
Brito, Lima, Cordeiro, Da, Nizer, Effectiveness of supplementation with quercetintype flavonols for treatment of viral lower respiratory tract infections: Systematic review and metaanalysis of preclinical studies, Phytotherapy Research: PTR,
doi:10.1002/ptr.7122
Campbell, Murata, Conner, Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19, PLoS One,
doi:10.1371/journal.pone.0267462.175
Chandan, Zemedikun, Thayakaran, Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19, Arthritis Rheumatol,
doi:10.1002/art.41593.170
Chandra, Das, Banday, Efficacy of polyherbal formulations for prevention of COVID-19 infection in high-risk subjects: A randomized open-label controlled clinical trial, Phytotherapy Research,
doi:10.1002/ptr.7531
Charfeddine, Hadj Amor, Jdidi, Long COVID 19 syndrome: is it related to microcirculation and endothelial dysfunction? Insights from TUN-EndCOV study, Front Cardiovasc. Med,
doi:10.3389/fcvm.2021.745758
Cheema, Sohail, Fatima, Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis, Rev Med Virol,
doi:10.1002/rmv.2427
Chen, Parthasarathy, Leung, Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection, Front Med,
doi:10.3389/fmed.2023.1227883.155
Chitre, Nadkarni, Jagtap, Phase III randomized clinical trial of BV-4051, an Ayurvedic polyherbal formulation in moderate SARS-CoV-2 infections and its impact on inflammatory biomarkers, Phytotherapy Research,
doi:10.1002/ptr.7683
Choudhury, Shabnam, Ahsan, Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient,
doi:10.3329/brc.v7i1.54245
Cohen, Brown, Rebound of COVID-19 With Nirmatrelvir-Ritonavir Antiviral Therapy, Ann Intern Med,
doi:10.7326/M23-2887
Daneshfard, Aghanouri, Kazemnejad, Effect of Sinamaz nasal drop on asymptomatic family members of COVID 19 patients: An open-label randomized controlled trial, Phytotherapy Research,
doi:10.1002/ptr.7915
Darban, Malek, Memarian, Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial, Journal of Cellular & Molecular Anesthesia
Dehzad, Ghalandari, Nouri, Askarpour, Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials, Cytokine
Delić, Matetic, Domjanović, Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial, Microorganisms,
doi:10.3390/microorganisms10061118
Derosa, Maffioli, Angelo, Pierro, A role for quercetin in coronavirus disease 2019 (COVID-19), Phytotherapy Research: PTR,
doi:10.1002/ptr.6887
Doherty, Hawkey, Goulder, A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain, Ann Rheum Dis,
doi:10.1136/ard.2011.154047.183
Edelstein, Boucau, Uddin, SARS-CoV-2 Virologic Rebound With Nirmatrelvir-Ritonavir Therapy: An Observational Study, Ann Intern Med,
doi:10.7326/M23-1756
Eggers, Eickmann, Zorn, Rapid and effective virucidal activity of povidone-iodine products against Middle East respiratory syndrome coronavirus (MERS-CoV) and modified vaccinia virus Ankara (MVA), Infect. Dis. Ther
El-Badrawy, Saleh, El-Badrawy, Role of Sodium Bicarbonate as Adjuvant Treatment of Nonsevere Computed Tomography-identified COVID-19 Pneumonia: A Preliminary Report, Indian Journal of Respiratory Care
Elsersy, Zahran, Elbakry, Combined Nasal, Oropharyngeal Povidone Iodine Plus Glycyrrhizic Acid Sprays, Accelerate Clinical and Laboratory Recovery and Reduces Household Transmission of SARS-CoV-2: A Randomized Placebo-Controlled Clinical Trial, Frontiers in Medicine,
doi:10.17219/dmp/150831
Elzein, Abdel-Sater, Fakhreddine, In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial, Journal of Evidence Based Dental Practice,
doi:10.1016/j.jebdp.2021.101584
Fantozzi, Pampena, Pierangeli, Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study, American Journal of Otolaryngology,
doi:10.1016/j.amjoto.2022.103549
Farnoosh, Akbariqomi, Badriet, Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial, Archives of Medical Research,
doi:10.1016/j.arcmed.2021.06.006
Farrell, Klatt-Cromwell, Schneider, Benefits and Safety of Nasal Saline Irrigations in a Pandemic-Washing COVID-19 Away, JAMA Otolaryngol Head Neck Surg,
doi:10.1001/jamaoto.2020.1622.128
Ferrer, Barrueco, Martinez-Beneyto, Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2, Scientific Reports,
doi:10.1038/s41598-021-03461-y
Fessler, Chang, Liu, Johnston, Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial, Nutrients,
doi:10.3390/nu15071548
Fiorentino, Coppola, Izzo, Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis, EClinicalMedicine,
doi:10.1016/j.eclinm.2021.101125
Fogleman, Cohen, Mercier, A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19, The Journal of the American Board of Family Medicine,
doi:10.3122/jabfm.2022.04.210529
Gambardella, Fiordelisi, Spigno, Effects of chronic supplementation of Larginine on physical fitness in water polo players, Oxid Med Cell Longev
García-García, Seco-Meseguer, Ruiz-Seco, Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial, Journal of Clinical Medicine,
doi:10.3390/jcm11041139
Guenezan, Garcia, Strasters, Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial, JAMA Otolaryngol Head Neck Surg,
doi:10.1001/jamaoto.2020.5490
Guervilly, Circulating endothelial cells as a marker of endothelial injury in severe COVID -19, J. Infect. Dis,
doi:10.1093/infdis/jiaa528
Gálvez-Barrón, Arroyo-Huidobro, Miňarro, COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study, Gerontology,
doi:10.1159/000515159.168
Gérain, Uebelhoer, Costes, NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial, Frontiers in Nutrition,
doi:10.3389/fnut.2023.1137407/full
Gérain, Uebelhoer, Costes, NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial, Frontiers in Nutrition,
doi:10.3389/fnut.2023.1137407/full
Gøtzsche, Why some of us no longer want to publish in prestigious medical journals
Haddad, Soliman, Wong, Fever integrates antimicrobial defences, inflammation control, and tissue repair in a cold-blooded vertebrate, Elife,
doi:10.7554/eLife.83644.180
Hansen, Mogensen, Agergaard, High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial, Lancet Reg Health Eur,
doi:10.1016/j.lanepe.2022.100539
Hartono, Suryawati, Sari, The Effect of Curcumin and Virgin Coconut Oil Towards Cytokines Levels in COVID-19 Patients at Universitas Sebelas Maret Hospital, Surakarta, Indonesia, Pharmacognosy Journal,
doi:10.5530/pj.2022.14.27
Hasan, Atrakji, Mehuaiden, The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients, International Journal of Infectious Diseases,
doi:10.1016/j.ijid.2021.10.012
Hasan, Chiu, Salamanca, Effects of Chlorhexidine and Povidone-Iodine on the SARS-CoV-2 Load: A Systematic Review and Meta-analysis, Eur J Dent,
doi:10.1055/s-0042-1753470.119
Hassaniazad, Eftekhar, Inchehsablagh, A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients, Phytotherapy Research,
doi:10.1002/ptr.7294
Hegde, Girisa, Bharathwajchetty, Vishwa, Kunnumakkara, Curcumin formulations for better bioavailability: what we learned from clinical trials thus far?, ACS Omega
Hellou, Mohsin, Elemy, Effect of ArtemiC in patients with COVID-19: A Phase II prospective study, Journal of Cellular and Molecular Medicine,
doi:10.1111/jcmm.17337
Ioannou, Berry, Rajeevan, Li, Mutalik et al., Effectiveness of Nirmatrelvir-Ritonavir Against the Development of Post-COVID-19 Conditions Among U.S. Veterans, Ann Intern Med,
doi:10.7326/M23-1394
Izzo, Trimarco, Mone, Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey, Pharmacol Res,
doi:10.1016/j.phrs.2022.106360
Jamir, Tripathi, Shankar, Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh,
doi:10.7759/cureus.20394
Kanjanawasee, Seresirikachorn, Chitsuthipakorn, Snidvongs, Hypertonic Saline Versus Isotonic Saline Nasal Irrigation: Systematic Review and Meta-analysis, Am J Rhinol Allergy
Karimi, Zarei, Soleymani, Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial, Phytotherapy Research,
doi:10.1002/ptr.7277
Karimpour-Razkenari, Naderi-Behdani, Salahshoor, Melatonin as adjunctive therapy in patients admitted to the Covid-19, Annals of Medicine and Surgery,
doi:10.1016/j.amsu.2022.103492
Kariwa, Fujii, Takashima, Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions, and chemical reagents, Jpn. J. Vet. Res
Khan, Iqtadar, Mumtaz, Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial, Frontiers in Pharmacology,
doi:10.3389/fphar.2022.898062/full
Khan, Iqtadar, Sami, Mumtaz, Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial, Frontiers in Pharmacology,
doi:10.3389/fphar.2022.898062/full
Khan, Ullah, Aschner, Cheang, Akkol, Neuroprotective effects of quercetin in Alzheimer's disease, Biomolecules,
doi:10.3390/biom10010059
Kim, Yoon, Lee, Lee, Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study, Int J Environ Res Public Health,
doi:10.3390/ijerph20053832.177
Kim, Yoon, Lee, Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study, Int J Environ Res Public Health,
doi:10.3390/ijerph20053832.174
Koshak, Koshak, Mobeireek, Nigella sativa for the treatment of COVID-19: An openlabel randomized controlled clinical trial, Complementary Therapies in Medicine,
doi:10.1016/j.ctim.2021.102769
Koshak, Koshak, Nigella sativa L as a potential phytotherapy for coronavirus disease 2019: a mini review of in silico studies, Curr Ther Res -Clin Exp,
doi:10.1016/j.curtheres.2020.100602
Koshak, Wei, Koshak, Nigella sativa supplementation improves asthma control and biomarkers: a randomized, double-blind, placebo-controlled trial, Phyther Res,
doi:10.1002/ptr.5761
Kritis, Karampela, Kokoris, Dalamaga, The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19, Metabol Open,
doi:10.1016/j.metop.2020.100066
Kunnumakkara, Bordoloi, Padmavathi, Monisha, Roy et al., the golden nutraceutical: Multitargeting for multiple chronic diseases, Br. J. Pharmacol
Lapi, Marconi, Grattagliano, To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case-control analysis, in primary care, Intern Emerg Med,
doi:10.1007/s11739-022-03054-1.153
Leal, Yu, Chen, Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis, COVID,
doi:10.3390/covid1010018
Lerner, Serret-Larmande, Rance, Mining Electronic Health Records for Drugs Associated With 28-day Mortality in COVID-19: Pharmacopoeia-wide Association Study (PharmWAS), JMIR Med Inform,
doi:10.2196/35190
Lucas, Czikora, Sridhar, Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury, Front Immunol,
doi:10.3389/fimmu.2013.00228
Macfadden, Brown, Buchan, Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications, Open Forum Infect Dis,
doi:10.1093/ofid/ofac156.173
Majdalawieh, Fayyad, Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: a comprehensive review, Int Immunopharmacol,
doi:10.1016/j.intimp.2015.06.023
Majeed, Nagabhushanam, Shah, A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients, Evidence-Based Complementary and Alternative Medicine,
doi:10.1155/2021/8447545
Matsuyama, Okura, Hashimoto, A prospective, randomized, open-label trial of early versus late povidone-iodine gargling in patients with COVID-19, Scientific Reports,
doi:10.1038/s41598-022-24683-8
Mehrbod, Abdalla, Fotouhi, Immunomodulatory properties of quercetin-3-O-α-L-rhamnopyranoside from Rapanea melanophloeos against influenza a virus, BMC Complementary and Alternative Medicine
Mody, Effect of 8.4% Soda-Bicarbonate Steam Inhalation on the Course of Disease in Mild to Moderate Cases of Covid-19, Acta Scientific Orthopaedics
Mohamed, Baharom, Sulaiman, Early viral clearance among COVID-19 patients when gargling with povidone-iodine and essential oils: a pilot clinical trial,
doi:10.1101/2020.09.07.20180448
Molla, Abul, Azad, A review on antiviral effects of Nigella Sativa L, Pharmacologyonline
Moreno-Martos, Verhamme, Ostropolets, Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe, Wellcome Open Res,
doi:10.12688/wellcomeopenres.17403.2.172
Mousavi, Heydari, Mehravaran, Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial, Journal of Medical Virology,
doi:10.1002/jmv.27312
Naghsh, Musazadeh, Nikpayam, Kavyani, Moridpour et al., Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials, Evid.-Based Complement. Altern. Med
Natto, Bakhrebah, Afeef, The short-term effect of different chlorhexidine forms versus povidone iodine mouth rinse in minimizing the oral SARS-CoV-2 viral load: An open label randomized controlled clinical trial study,
doi:10.22541/au.166675335.56566797/v1
Oei, Millar, Lily, Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study, Am J Clin Nutr,
doi:10.1016/j.ajcnut.2023.04.013
Oh, Song, Lee, Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study, Int J Environ Res Public Health,
doi:10.3390/ijerph18136804.171
Oikonomou, Souvaliotis, Lampsas, Endothelial dysfunction in acute and long standing COVID-19: a prospective cohort study, Vasc. Pharm,
doi:10.1016/j.vph.2022.106975
Onal, Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial, Turk. J. Biol
Pantazopoulos, Chalkias, Miziou, A Hypertonic Seawater Nasal Irrigation Solution Containing Algal and Herbal Natural Ingredients Reduces Viral Load and SARS-CoV-2 Detection Time in the Nasal Cavity, Journal of Personalized Medicine,
doi:10.3390/jpm13071093
Pawar, Mastud, Pawar, Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial, Frontiers in Pharmacology,
doi:10.3389/fphar.2021.669362/full
Peiris, Izcovich, Ordunez, Challenges to delivering evidence-based management for long COVID, BMJ Evidence-Based Medicine
Pierro, Derosa, Maffioli, 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,
doi:10.2147/IJGM.S318720
Pierro, Iqtadar, Khan, 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,
doi:10.2147/IJGM.S318949
Pierro, Khan, Iqtadar, Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial, Frontiers in Pharmacology
Prasad, Tyagi, Aggarwal, Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: The Golden Pigment from Golden Spice, Cancer Res. Treat
Qaseem, Yost, Miller, Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1), Ann Intern Med,
doi:10.7326/M22-2249
Ramalingam, Graham, Dove, A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold, Sci Rep,
doi:10.1038/s41598-018-37703-3.130
Ravichandran, Mohan, Sukumaran, An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients, Sci Rep,
doi:10.1038/s41598-022-10370-1
Ravichandran, Mohan, Sukumaran, An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients, Sci Rep,
doi:10.1038/s41598-022-10370-1
Razmpoosh, Safi, Abdollahi, The effect of Nigella sativa on the measures of liver and kidney parameters: a systematic review and meta-analysis of randomized-controlled trials, Pharmacol Res,
doi:10.1016/j.phrs.2020.104767
Rees, Rostad, Mantus, Altered amino acid profile in patients with SARS-CoV-2 infection, Proc Natl Acad Sci
Reizine, Lesouhaitier, Gregoire, SARS-CoV-2-induced ARDS associates with MDSC expansion, lymphocyte dysfunction, and arginine shortage, J Clin Immunol
Ritsinger, Bodegård, Kristofi, History of heart failure and chronic kidney disease and risk of all-cause death after COVID-19 during the first three waves of the pandemic in comparison with influenza outbreaks in Sweden: a registry-based, retrospective, case-control study, BMJ Open,
doi:10.1136/bmjopen-2022-069037.178
Rondanelli, Perna, Gasparri, Promising Effects of 3-Month Period of Quercetin Phytosome® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study, Life,
doi:10.3390/life12010066
Sacchi, Grassi, Notari, Expansion of myeloid derived suppressor cells contributes to platelet activation by L-Arginine deprivation during SARS-CoV-2 infection, Cells,
doi:10.3390/cells10082111
Sadeghizadeh, Asadollahi, Jahangiri, Promising clinical outcomes of nano-curcumin treatment as an adjunct therapy in hospitalized COVID-19 patients: A randomized, double-blinded, placebocontrolled trial, Phytotherapy Research,
doi:10.1002/ptr.7844
Said, Abdulbaset, El-Kholy, The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial, Frontiers in Pharmacology,
doi:10.3389/fphar.2022.1011522/full
Sankhe, Memane, Gawali, A Randomized, Controlled, Blinded, Parallel Group, Clinical Trial to study the role of Ayurcov (AyurCoro3), one day regimen as an adjuvant therapy for COVID-19 disease management, at dedicated Covid Hospital (DCH) in India, Complementary Therapies in Medicine,
doi:10.1016/j.ctim.2022.102824
Sankhe, Memane, Gawali, A prospective, multi center, single blind, randomized controlled study evaluating "AyurCoro3" as an adjuvant in the treatment of mild to moderate COVID, Journal of Ayurveda and Integrated Medical Sciences,
doi:10.21760/jaims.6.4.6
Seet, Quek, Ooi, Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial, International Journal of Infectious Diseases,
doi:10.1016/j.ijid.2021.04.035
Seneviratne, Balan, Ko, Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore, Infection
Setayesh, Karimi, Zargaran, Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): a randomized clinical trial, Integrative Medicine Research
Sharif, Opu, Khan, Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study, Nutrients,
doi:10.3390/nu14235029.154
Shohan, Nashibi, Mahmoudian-Sani, The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial, European Journal of Pharmacology,
doi:10.1016/j.ejphar.2021.174615
Soares, Da Silva, Soares, Preliminary observation of the use of sodium bicarbonate solution as an adjunct in the treatment of coronavirus 2019 disease (COVID-19): prognosis improvement in patients requiring intensive care / Observação preliminar do uso de solução de bicarbonato de sódio como coadjuvante no tratamento da doença coronavírus 2019 (COVID-19): melhora do prognóstico na necessidade de terapia intensiva, Brazilian Journal of Development,
doi:10.34117/bjdv7n12-039
Sobhy, Saleh, Abdelatty, Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial, Open Anesthesia Journal
Stufano, Isgrò, Palese, Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers, Int J Mol Sci
Sulistyani, Julia, Soeprapto, The effects of mouth rinsing and gargling with mouthwash containing povidone-iodine and hydrogen peroxide on the cycle threshold value of Severe Acute Respiratory Syndrome Coronavirus 2: A randomized controlled trial of asymptomatic and mildly symptomatic patients, Research,
doi:10.12688/f1000research.110843.1
Sánchez-González, Mahıllo-Fernandez, Villar-Alvarez, What if melatonin could help COVID-19 severe patients?,
doi:10.5664/jcsm.9554
Sánchez-Rico, De La Muela, Herrera-Morueco, Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study, Journal of Travel Medicine,
doi:10.1093/jtm/taab195/6523003
Tahmasebi, Saeed, Temirgalieva, Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2, Life Sciences
Thimmulappa, Mudnakudu-Nagaraju, Shivamallu, Subramaniam, Radhakrishnan et al., Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19, Heliyon
Thomas, Williams, Aldous, A Randomised, Double-Blind, Placebo-Controlled Trial Evaluating Concentrated Phytochemical-Rich Nutritional Capsule in Addition to a Probiotic Capsule on Clinical Preprints,
doi:10.3390/covid2040031
Tosato, Calvani, Picca, Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial, Nutrients,
doi:10.3390/nu14234984
Ujjan, Khan, Nigar, The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial, Frontiers in Nutrition,
doi:10.3389/fnut.2022.1023997/full
Ujjan, Khan, Nigar, The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial, Frontiers in Nutrition,
doi:10.3389/fnut.2022.1023997/full
Valizadeh, Abdolmohammadi-Vahid, Danshina, Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients, Int. Immunopharmacol,
doi:10.1016/j.intimp.2020.107088
Vlachou, Siamidi, Dedeloudi, Konstantinidou, Papanastasiou, Pineal hormone melatonin as an adjuvant treatment for COVID-19 (Review), Int. J. Mol. Med,
doi:10.3892/ijmm.2021.4880
Wang, Zhang, Zhang, Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients, Front Public Health,
doi:10.3389/fpubh.2023.1145669.124
Who, A clinical case definition of post COVID-19 condition by a Delphi consensus
Wijnands, Castermans, Hommen, Meesters, Poeze, Arginine and citrulline and the immune response in sepsis, Nutrients,
doi:10.3390/nu7031426
Xie, Brash, Turkmen, Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study, Drugs
Xu, Shi, Wang, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, The Lancet Respiratory Medicine,
doi:10.1016/S2213-2600(20)30076-X
Zarabanda, Vukkadala, Phillips, The Effect of Povidone-Iodine Nasal Spray on COVID-19 Nasopharyngeal Viral Load in Patients: A Randomized Control Trial, Laryngoscope,
doi:10.1002/lary.29935
{ 'indexed': { 'date-parts': [[2023, 12, 18]],
'date-time': '2023-12-18T05:06:12Z',
'timestamp': 1702875972826},
'posted': {'date-parts': [[2023, 12, 15]]},
'group-title': 'Public Health and Healthcare',
'reference-count': 0,
'publisher': 'MDPI AG',
'license': [ { 'start': { 'date-parts': [[2023, 12, 15]],
'date-time': '2023-12-15T00:00:00Z',
'timestamp': 1702598400000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by/4.0'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'accepted': {'date-parts': [[2023, 12, 14]]},
'abstract': '<jats:p>The official recommendations to manage COVID-19 in the outpatient setting focus on '
'high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many '
'problems. 
\n'
'Therefore, one may consider also other treatments meeting these criteria: 
\n'
'• promising effectiveness, based on favorable randomized controlled trials (RCTs) of '
'sufficient validity. Even without definitive evidence, physicians and informed patients can '
'consider them if they are also: 
\n'
'• safe, to the state of knowledge
\n'
'• with a very favorable opportunity cost
\n'
'• biologically plausible/not implausible
\n'
'• accessible
\n'
'• without major commercial sponsors in the trials promoting them, and with researchers '
'without major conflicts of interests.
\n'
'The main focus is on a limited group of functional foods and some their active ingredients, '
'with further mention of other substances of different origin, yet fully meeting all the '
'aforementioned criteria. 
\n'
'The functional foods and substances described and discussed certainly do not cover all the '
'known effective therapies for COVID-19 (in one case also for Long-COVID), but the only '
'therapies proposed in this paper currently satisfy all the above criteria.
\n'
'The supporting scientific evidence will favor meta-analyses of RCTs that include the most '
'definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people '
'tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most '
'valid design, i.e. RCTs.</jats:p>',
'DOI': '10.20944/preprints202312.1178.v1',
'type': 'posted-content',
'created': { 'date-parts': [[2023, 12, 18]],
'date-time': '2023-12-18T00:49:32Z',
'timestamp': 1702860572000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Neglected Effective Early Therapies against COVID-19: Focus on Functional Foods and Related '
'Active Substances. A Review',
'prefix': '10.20944',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-4365-6814',
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'given': 'Alberto',
'family': 'Donzelli',
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'deposited': { 'date-parts': [[2023, 12, 18]],
'date-time': '2023-12-18T00:51:07Z',
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'score': 1,
'resource': {'primary': {'URL': 'https://www.preprints.org/manuscript/202312.1178/v1'}},
'subtitle': [],
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'issued': {'date-parts': [[2023, 12, 15]]},
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'URL': 'http://dx.doi.org/10.20944/preprints202312.1178.v1',
'relation': {},
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'published': {'date-parts': [[2023, 12, 15]]},
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