Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment
Review mSystems . 2021 May 4;6(3):e00122-21. doi: 10.1128/mSystems.00122-21
Ronan Lordan 1, Halie M Rando 2 3 4, COVID-19 Review Consortium; Casey S Greene 5 3 4 6
Virus and Zinc:
- COVID was associated with low Vitamin D or Zinc – umbrella review Feb 2023
- 23 COVID mitigation strategies: at least 6 of which increase Vitamin D in cells - Sept 2022
- COVID and Zinc - many studies
- Surviving COVID with vitamins and minerals is not a myth – June 2022
- Vitamin D, Zinc, Magnesium etc. are needed to fight COVID – April 2022
- How vitamins D, C, Zinc, and Selenium might fight COVID - Dec 2021
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- COVID-19 decreased risk if add Vitamin D, A, C, NAC, Se, Zn, or Omega-3 – Dec 2021
- COVID-19 patients had low levels of Zinc, Vitamin A, Vitamin D, and Vitamin C – Sept 2021
- COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
- Vitamin D, C, A, and E, as well as Iron, Se, and Zinc each augment vaccine response – July 2021
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 etc. – June 2021
- COVID-19 treatment outside of hospital – Vitamin D, zinc, etc. – May 2021
- Important Role of Micronutrients during COVID-19 (Zinc, Vitamin D, C, Folate) – May 5, 2021
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- Zinc therapy for COVID-19 – Feb 2021
- COVID-19 alternative treatments - real-time database
- Overview of reviews of COVID-19 and vitamin D, etc. – April 2021
- COVID-19 what it is, prevention by Functional Nutrition doctor - Feb 2021
- Vitamin D, Zinc, etc. look promising for COVID-19 (Holick) - Jan 25, 2021
- Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
- Micronutrients for COVID-19: Vitamin D, Vitamin C, Melatonin, Zinc, Se, etc. - Dec 2020
- Zinc (which increases vitamin D in tissues) may both prevent and treat COVID-19
- COVID-19 possible therapies: Vitamin D, Selenium, Zinc, Vitamin C, Potassium, Resveratrol , etc.– Aug 5, 2020
- 7 reasons to think that Zinc should fight COVID-19 – July 2020
- Observations that Vitamin D, Zinc, and Selenium separately reduce COVID-19 – Aug 7, 2020
- Mild COVID-19 quickly treated by Zinc lozenges in 4 people – June 6, 2020
- Zinc, respiratory tract infections and COVID-19 – July 2020
- Fight COVID-19 with Vitamin D, Vitamin C, Zinc, Selenium, Resveratrol, etc. - Sardi May 12, 2020
- Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
- Loss of smell may be related to low Zinc or perhaps low vitamin D
- Dengue fever immune response and micronutrients (vitamins D, E, A, and Zinc, Iron, Chromium) – Nov 2015
- Overview Colds and flu and Vitamin D
Virus and Omega-3:
- How vitamins A, B, C, D, E, F (Omega), K fight COVID - Feb 2022
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- Omega-3 decreases heart disease and COVID: Harris and Patrick, video and transcript - Dec 2021
- COVID-19 decreased risk if add Vitamin D, A, C, NAC, Se, Zn, or Omega-3 – Dec 2021
- High-dose Omega-3 fought COVID in 2 hospital trials (6x reduction in ICU, reduced time) – Masterjohn Oct 2021
- COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
- Omega-3 reduces risk of COVID-19 - many studies
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 etc. – June 2021
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
- COVID-19 ICU survival rate increased 7X by daily Omega-3 – RCT March 2021
- 4X fewer COVID-19 deaths in those having high Omega-3 index – Jan 6, 2021
Virus and Resveratrol:
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- COVID-19 appears reduced by Resveratrol plus 100K IU of vitamin D – Small RCT Sept 2021
- COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
- COVID-19 what it is, prevention by Functional Nutrition doctor - Feb 2021
- Vitamin D Receptor activation should reduce ARDS associated with COVID-19 - June 2020
- COVID-19 possible therapies: Vitamin D, Selenium, Zinc, Vitamin C, Potassium, Resveratrol , etc.– Aug 5, 2020
- Fight COVID-19 with Vitamin D, Vitamin C, Zinc, Selenium, Resveratrol, etc. - Sardi May 12, 2020
Virus and Magnesium:
- Long-COVID 3.1 X more likely if insufficient amounts of Magnesium and Vitamin D – March 2024
- COVID appears to be treated by many antioxidants (Vitamins D, C, E, K, and Quercetin, Curcumin, etc) – Jan 2023
- Fatigue and other long-haul problems appear to be associated with low Magnesium - Chambers Oct 2022
- Low Magnesium associated with severe COVID – many studies
- COVID and Magnesium - hypothesis, clinical trials, Long-Haul - Oct 2021
- COVID treatment patent applied for - using Rutin, Vitamin D, Vitamin C, Magnesium, etc. – April 2022
- COVID death 6.9X less likely if high Magnesium to Calcium ratio – April 2022
- Hypothesis: 2 long-haul COVIDs: had mild symptoms and had needed ICU - April 2022
- Excess Magnesium is bad for health (COVID hospital days in this case) – April 2022
- Vitamin D, Zinc, Magnesium etc. are needed to fight COVID – April 2022
- Long Covid, Short Magnesium - Chambers April 2022
- Lower Magnesium, 6 percent more COVID - Feb 2022
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 etc. – June 2021
- Elderly nutrition and COVID-19 – systematic review July 2021
- Magnesium in Infectious Diseases in Older People - Jan 2021
- COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
- 6X less risk of COVID-19 ICU if Vitamin D and Vit B12 and Mg – Jan 2021
- Cytokine storms (COVID-19, etc.) eliminated by Vitamin D (Magnesium helps)
- Magnesium and Vitamin D deficiencies associated with worse COVID-19 – Jan, 2021
- Excessive insulin decreases vitamin D in 4 ways – problems for diabetic COVID-19 – Dec 2020
- Magnesium (which increases vitamin D) may fight COVID-19 - Oct 2020
- COVID-19 1.8 X more likely if proton pump inhibitor (decreases Mg and Vitamin D) – Aug 2020
- COVID-19 might be treated with Mg IV and Potassium – July 2020
- COVID-19 prompts awareness of deficiencies of Vitamin D, C and Magnesium - April 6 2020
- Obesity pandemic since 1975 - is it due to Vitamin D, Magnesium, Iodine, adenovirus, or what
Virus and Probiotics:
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- COVID Long-Haul fought by probiotics - Jan 2022
- Tested positive for COVID, taking probiotics stopped symptoms 5 days sooner - RCT Jan 2022
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
See also COVID-19 risks reduced by Vitamin D, Magnesium, Zinc, Resveratrol, Omega-3, etc. (auto-updated)
COVID-19 treated by Vitamin D - studies, reports, videos
- As of March 31, 2024, the VitaminDWiki COVID page had: trial results, meta-analyses and reviews, Mortality studies see related: Governments, HealthProblems, Hospitals, Dark Skins, All 26 COVID risk factors are associated with low Vit D, Fight COVID-19 with 50K Vit D weekly Vaccines Take lots of Vitamin D at first signs of COVID 166 COVID Clinical Trials using Vitamin D (Aug 2023) Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
5 most-recently changed Virus entries
 Download the PDF from VitaminDWiki
Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic's devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, Vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products may help alleviate deficiencies. For example, evidence indicates that Vitamin D deficiency may be associated with a greater incidence of infection and severity of COVID-19, suggesting that Vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending Vitamin D supplementation to those at high risk of COVID-19. Because research in Vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis.I
MPORTANCE Sales of dietary supplements and nutraceuticals have increased during the pandemic due to their perceived "immune-boosting" effects. However, little is known about the efficacy of these dietary supplements and nutraceuticals against the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) or the disease that it causes, CoV disease 2019 (COVID-19). This review provides a critical overview of the potential prophylactic and therapeutic value of various dietary supplements and nutraceuticals from the evidence available to date. These include vitamin C, Vitamin D, and zinc, which are often perceived by the public as treating respiratory infections or supporting immune health. Consumers need to be aware of misinformation and false promises surrounding some supplements, which may be subject to limited regulation by authorities. However, considerably more research is required to determine whether dietary supplements and nutraceuticals exhibit prophylactic and therapeutic value against SARS-CoV-2 infection and COVID-19. This review provides perspective on which nutraceuticals and supplements are involved in biological processes that are relevant to recovery from or prevention of COVID-19.
References (vitamin D occurs 52 times)
- Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: the inflammation link and the role of nutrition in potential mitigation. Nutrients. 2020;12:1466. - DOI
- James PT, Zakari A, Armitage AE, Bonell A, Cerami C, Drakesmith H, Jobe M, Jones KS, Liew Z, Moore SE, Morales-Berstein F, Nabwera HM, Nadjim B, Pasricha S-R, Scheelbeek P, Silver MJ, Teh MR, Prentice AM. Could nutrition modulate COVID-19 susceptibility and severity of disease? A systematic review. medRxiv. 2020.
- Silverio R, Gonçalves DC, Andrade MF, Marilia S. Coronavirus disease 2019 (COVID-19) and nutritional status: the missing link?. Adv Nutr. 2020. - DOI
- Jae HI, Young SJ, Jihyeon B, Moon-Hyun C, Hea YK, Jin-Soo L. Nutritional status of patients with COVID-19. Int J Infect Dis. 2020;100:390–393. - DOI
- Calder P, Carr A, Gombart A, Eggersdorfer M. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 2020;12:1181. - DOI
- Grebow J. Peak dietary supplement sales leveling off during COVID-19 pandemic, but growth still remains strong over last year, market researchers report during webcast. 2020.
- Zhao A, Li Z, Ke Y, Huo S, Ma Y, Zhang Y, Zhang J, Ren Z. Dietary diversity among Chinese residents during the COVID-19 outbreak and its associated factors. Nutrients. 2020;12:1699. - DOI
- Koe T. Lockdown impact: grocery stores bolstered NZ supplements sales as pharmacies slumped. 2020.
- COVID-19 temporarily bolsters European interest in supplements. 2020.
- Koe T. India’s immune health surge: nation leads APAC in number of new product launches—new data. 2020.
- Ayseli YI, Aytekin N, Buyukkayhan D, Aslan I, Ayseli MT. Food policy, nutrition and nutraceuticals in the prevention and management of COVID-19: advice for healthcare professionals. Trends Food Sci Technol. 2020;105:186–199. - DOI
- Furlong C. 5 food and beverage trends in Europe during COVID-19. 2020.
- McClements DJ, Decker EA, Park Y, Weiss J. Structural design principles for delivery of bioactive components in nutraceuticals and functional foods. Crit Rev Food Sci Nutr. 2009;49:577–606. - DOI
- Moss JWE, Ramji DP. Nutraceutical therapies for atherosclerosis. Nat Rev Cardiol. 2016;13:513–532. - DOI
- Kalra EK. Nutraceutical—definition and introduction. AAPS PharmSci. 2015;5:E25. - DOI
- Dietary Supplement Health and Education Act of 1994. 1994.
- Food and Drug Administration Modernization Act (FDAMA) of 1997. 2018.
- Santini A, Novellino E. Nutraceuticals—shedding light on the grey area between pharmaceuticals and food. Expert Rev Clin Pharmacol. 2018;11:545–547. - DOI
- Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. 2002.
- Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. 2004.
- Regulation (EC) no 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. 2006.
- Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. 2006.
- Santini A, Cammarata SM, Capone G, Ianaro A, Tenore GC, Pani L, Novellino E. Nutraceuticals: opening the debate for a regulatory framework. Br J Clin Pharmacol. 2018;84:659–672. - DOI
- Stefanie B, Sukhada K, Stefano C. Reviewing the Nutrition and Health Claims Regulation (EC) no. 1924/2006: what do we know about its challenges and potential impact on innovation?. Int J Food Sci Nutr. 2016;68:1–9. - DOI
- Dwyer J, Coates P, Smith M. Dietary supplements: regulatory challenges and research resources. Nutrients. 2018;10:41. - DOI
- Warning letter. Noetic Nutraceuticals. 2020.
- 2020.
- Warning letter. Spartan Enterprises Inc. dba Watershed Wellness Center. 2020.
- FTC sues California marketer of $23,000 COVID-19 “treatment” plan. 2020.
- Halford B. What is oleandrin, the compound touted as a possible COVID-19 treatment?. Chem Eng News. 2020.
- Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020;395:e35–e36. - DOI
- Infusino F, Marazzato M, Mancone M, Fedele F, Mastroianni CM, Severino P, Ceccarelli G, Santinelli L, Cavarretta E, Marullo AGM, Miraldi F, Carnevale R, Nocella C, Biondi-Zoccai G, Pagnini C, Schiavon S, Pugliese F, Frati G, d’Ettorre G. Diet supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection: a scoping review. Nutrients. 2020;12:1718. - DOI
- Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J Med Virol. 2020;92:479–490. - DOI
- McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Cardiovasc Dis. 2020;63:383–385. - DOI
- Lordan R, Redfern S, Tsoupras A, Zabetakis I. Inflammation and cardiovascular disease: are marine phospholipids the answer?. Food Funct. 2020;11:2861–2885. - DOI
- Szabó Z, Marosvölgyi T, Szabó É, Bai P, Figler M, Verzár Z. The potential beneficial effect of EPA and DHA supplementation managing cytokine storm in coronavirus disease. Front Physiol. 2020;11:752. - DOI
- Saha SK, Murray P. Exploitation of microalgae species for nutraceutical purposes: cultivation aspects. Fermentation. 2018;4:46. - DOI
- Ratha SK, Renuka N, Rawat I, Bux F. Prospective options of algae-derived nutraceuticals as supplements to combat COVID-19 and human coronavirus diseases. Nutrition. 2021;83:111089. - DOI
- Schmidt EB, Møller JM, Svaneborg N, Dyerberg J. Safety aspects of fish oils. Drug Invest. 2012;7:215–220. - DOI
- Update on seafood consumption during pregnancy. 2017.
- Greenberg JA, Bell SJ, Van Ausdal W. Omega-3 fatty acid supplementation during pregnancy. Rev Obstet Gynecol. 2008;1:162–169.
- Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?. Br J Clin Pharmacol. 2013;75:645–662. - DOI
- Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015;1851:469–484. - DOI
- Whelan J, Gowdy KM, Shaikh SR. N-3 polyunsaturated fatty acids modulate B cell activity in pre-clinical models: implications for the immune response to infections. Eur J Pharmacol. 2016;785:10–17. - DOI
- Asher A, Tintle NL, Myers M, Lockshon L, Bacareza H, Harris WS. Blood omega-3 fatty acids and death from COVID-19: a pilot study. Prostaglandins Leukot Essent Fatty Acids. 2021;166:102250. - DOI
- Tian T, Zhao Y, Huang Q, Li J. n-3 Polyunsaturated fatty acids improve inflammation via inhibiting sphingosine kinase 1 in a rat model of parenteral nutrition and CLP-induced sepsis. Lipids. 2016;51:271–278. - DOI
- Das UN. Polyunsaturated fatty acids and sepsis. Nutrition. 2019;65:39–43. - DOI
- Zhang B, Zhou X, Qiu Y, Song Y, Feng F, Feng J, Song Q, Jia Q, Wang J. Clinical characteristics of 82 cases of death from COVID-19. PLoS One. 2020;15:e0235458. - DOI
- Sabater J, Masclans J, Sacanell J, Chacon P, Sabin P, Planas M. Effects of an omega-3 fatty acid-enriched lipid emulsion on eicosanoid synthesis in acute respiratory distress syndrome (ARDS): a prospective, randomized, double-blind, parallel group study. Nutr Metab (Lond). 2011;8:22. - DOI
- Dushianthan A, Cusack R, Burgess VA, Grocott MP, Calder P. Immunonutrition for adults with ARDS: results from a Cochrane systematic review and meta-analysis. Respir Care. 2020;65:99–110. - DOI
- Chen HS, Wang S, Zhao Y, Luo YT, Tong H, Su L. Correlation analysis of omega-3 fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from previous randomized controlled trials. Nutr J. 2018;17:57. - DOI
- Buckley CD, Gilroy DW, Serhan CN. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity. 2014;40:315–327. - DOI
- Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol. 2015;16:51–67. - DOI
- Sandhaus S, Swick AG. Specialized proresolving mediators in infection and lung injury. Biofactors. 2020;47:6–18. - DOI
- Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510:92–101. - DOI
- Ramon S, Baker SF, Sahler JM, Kim N, Feldsott EA, Serhan CN, Martínez-Sobrido L, Topham DJ, Phipps RP. The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?. J Immunol. 2014;193:6031–6040. - DOI
- Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, Watanebe T, Sakabe S, Daidoji T, Nakamura S, Kadowaki A, Ohto T, Nakanishi H, Taguchi R, Nakaya T, Murakami M, Yoneda Y, Arai H, Kawaoka Y, Penninger JM, Arita M, Imai Y. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112–125. - DOI
- Panigrahy D, Gilligan MM, Huang S, Gartung A, Cortés-Puch I, Sime PJ, Phipps RP, Serhan CN, Hammock BD. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?. Cancer Metastasis Rev. 2020;39:337–340. - DOI
- Regidor P-A, Santos FG, Rizo JM, Egea FM. Pro resolving inflammatory effects of the lipid mediators of omega 3 fatty acids and its implication in SARS COVID-19. Med Hypotheses. 2020;145:110340. - DOI
- Pal A, Gowdy KM, Oestreich KJ, Beck M, Shaikh SR. Obesity-driven deficiencies of specialized pro-resolving mediators may drive adverse outcomes during SARS-CoV-2 infection. Front Immunol. 2020;11:1997. - DOI
- Schwerbrock NMJ, Karlsson EA, Shi Q, Sheridan PA, Beck MA. Fish oil-fed mice have impaired resistance to influenza infection. J Nutr. 2009;139:1588–1594. - DOI
- Husson M-O, Ley D, Portal C, Gottrand M, Hueso T, Desseyn J-L, Gottrand F. Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect. 2016;73:523–535. - DOI
- Skarke C, Alamuddin N, Lawson JA, Li X, Ferguson JF, Reilly MP, FitzGerald GA. Bioactive products formed in humans from fish oils. J Lipid Res. 2015;56:1808–1820. - DOI
- Bäck M. Resolving inflammatory storm in COVID-19 patients by omega-3 polyunsaturated fatty acids—a single-blind, randomized, placebo-controlled feasibility study. 2020.
- Arnardottir H, Pawelzik S-C, Wistbacka UÖ, Artiach G, Hofmann R, Reinholdsson I, Braunschweig F, Tornvall P, Religa D, Bäck M. Stimulating the resolution of inflammation through omega-3 polyunsaturated fatty acids in COVID-19: rationale for the COVID-Omega-F Trial. Front Physiol. 2021;11:624657. - DOI
- Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135:2033–2040. - DOI
- Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020;50:54–67. - DOI
- Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian CD, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quéré I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020;75:2950–2973. - DOI
- Tsoupras A, Lordan R, Zabetakis I. Thrombosis and COVID-19: the potential role of nutrition. Front Nutr. 2020;7:583080. - DOI
- Adili R, Hawley M, Holinstat M. Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids. Prostaglandins Other Lipid Mediat. 2018;139:10–18. - DOI
- Lordan R, Tsoupras A, Zabetakis I. Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: potential role of antiplatelet agents. Blood Rev. 2021;45:100694. - DOI
- An investigation on the effects of icosapent ethyl (VascepaTM) on inflammatory biomarkers in individuals with COVID-19. 2020.
- Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif J-C, Ballantyne CM. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22. - DOI
- A randomised, double-blind, placebo controlled study of eicosapentaenoic acid (EPA-FFA) gastro-resistant capsules to treat hospitalised subjects with confirmed SARS-CoV-2. 2020.
- Abulmeaty M. Anti-inflammatory/antioxidant oral nutrition supplementation on the cytokine storm and progression of COVID-19 (ONSCOVID19). 2020.
- Messina G, Polito R, Monda V, Cipolloni L, Di Nunno N, Di Mizio G, Murabito P, Carotenuto M, Messina A, Pisanelli D, Valenzano A, Cibelli G, Scarinci A, Monda M, Sessa F. Functional role of dietary intervention to improve the outcome of COVID-19: a hypothesis of work. Int J Mol Sci. 2020;21:3104. - DOI
- Maares M, Haase H. Zinc and immunity: an essential interrelation. Arch Biochem Biophys. 2016;611:58–65. - DOI
- von Bülow V, Dubben S, Engelhardt G, Hebel S, Plümäkers B, Heine H, Rink L, Haase H. Zinc-dependent suppression of TNF-α production is mediated by protein kinase A-induced inhibition of Raf-1, IκB kinase β, and NF-κB. J Immunol. 2007;179:4180–4186. - DOI
- Prasad AS, Bao B, Beck FWJ, Sarkar FH. Zinc activates NF-κB in HUT-78 cells. J Lab Clin Med. 2001;138:250–256. - DOI
- Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44–49. - DOI
- Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, Cardozo LJ. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85:837–844. - DOI
- Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Adv Nutr. 2019;10:696–710. - DOI
- Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc. 2004;44:594–603. - DOI
- Hemilä H. Zinc lozenges may shorten the duration of colds: a systematic review. Open Respir Med J. 2011;5:51–58. - DOI
- Jothimani D, Kailasam E, Danielraj S, Nallathambi B, Ramachandran H, Sekar P, Manoharan S, Ramani V, Narasimhan G, Kaliamoorthy I, Rela M. COVID-19: poor outcomes in patients with zinc deficiency. Int J Infect Dis. 2020;100:343–349. - DOI
- Te Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6:e1001176. - DOI
- Báez-Santos YM, St John SE, Mesecar AD. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res. 2015;115:21–38. - DOI
- Avni T. A randomized study evaluating the safety and efficacy of hydroxychloroquine and zinc in combination with either azithromycin or doxycycline for the treatment of COVID-19 in the outpatient setting. 2020.
- A study of hydroxychloroquine and zinc in the prevention of COVID-19 infection in military healthcare workers (COVID-Milit). 2020.
- International ALLIANCE Study of therapies to prevent progression of COVID-19. 2020.
- Early intervention in COVID-19: favipiravir verses standard care (PIONEER).
- Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Lisboa T, Junqueira DLM, de Barros e Silva PGM, Tramujas L, Abreu-Silva EO, Laranjeira LN, Soares AT, Echenique LS, Pereira AJ, Freitas FGR, Gebara OCE, Dantas VCS, Furtado RHM, Milan EP, Golin NA, Cardoso FF, Maia IS, Hoffmann Filho CR, Kormann APM, Amazonas RB, Bocchi de Oliveira MF, Serpa-Neto A, Falavigna M, Lopes RD, Machado FR, Berwanger O. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383:2041–2052. - DOI
- Lewis K, Chaudhuri D, Alshamsi F, Carayannopoulos L, Dearness K, Chagla Z, Alhazzani Wfor the GUIDE Group. The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis: a systematic review and meta-analysis of randomized trials. PLoS One. 2021;16:e0244778. - DOI
- Fiolet T, Guihur A, Rebeaud ME, Mulot M, Peiffer-Smadja N, Mahamat-Saleh Y. Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Clin Microbiol Infect. 2021;27:19–27. - DOI
- Carlucci PM, Ahuja T, Petrilli C, Rajagopalan H, Jones S, Rahimian J. Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients. J Med Microbiol. 2020;69:1228–1234. - DOI
- Yao JS, Paguio JA, Dee EC, Tan HC, Achintya M, Carmelo M, Jerry J, Penna ND, Celi LA. The minimal effect of zinc on the survival of hospitalized patients with COVID-19. Chest. 2021;159:108–111. - DOI
- Desai M. Coronavirus disease 2019—using ascorbic acid and zinc supplementation (COVIDAtoZ). 2021.
- Naveen N, Nair DT. Vitamin B12 may inhibit RNA-dependent-RNA polymerase activity of nsp12 from the COVID-19 virus. 2020.
- Giuseppe C, Massimo N, Mauro P, Michela P, Simone P, Giorgio L, Mariangela R, Hellas C, D’Antona G. The long history of vitamin C: from prevention of the common cold to potential aid in the treatment of COVID-19. Front Immunol. 2020;11:574029. - DOI
- Carr AC, Rowe S. The emerging role of vitamin C in the prevention and treatment of COVID-19. Nutrients. 2020;12:3286. - DOI
- Chen Y, Luo G, Yuan J, Wang Y, Yang X, Wang X, Li G, Liu Z, Zhong N. Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages. Mediators Inflamm. 2014;2014:426740. - DOI
- Hagel AF, Layritz CM, Hagel WH, Hagel H-J, Hagel E, Dauth W, Kressel J, Regnet T, Rosenberg A, Neurath MF, Molderings GJ, Raithel M. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:789–793. - DOI
- Carr A, Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. - DOI
- Hume R, Weyers E. Changes in leucocyte ascorbic acid during the common cold. Scott Med J. 2016;18:3–7. - DOI
- Wilson CWM. Ascorbic acid function and metabolism during colds. Ann N Y Acad Sci. 1975;258:529–539. - DOI
- Davies JEW, Hughes RE, Jones E, Reed SE, Craig JW, Tyrrell DAJ. Metabolism of ascorbic acid (vitamin C) in subjects infected with common cold viruses. Biochem Med. 1979;21:78–85. - DOI
- Hemilä H. Vitamin C and infections. Nutrients. 2017;9:339. - DOI
- Hemilä H. Vitamin C and the common cold. Brit J Nutr. 2007;67:3–16. - DOI
- Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients. 2019;11:708. - DOI
- Arvinte C, Singh M, Marik PE. Serum levels of vitamin C and Vitamin D in a cohort of critically ill COVID-19 patients of a North American community hospital intensive care unit in May 2020: a pilot study. Med Drug Discov. 2020;8:100064. - DOI
- Chiscano-Camón L, Ruiz-Rodriguez JC, Ruiz-Sanmartin A, Roca O, Ferrer R. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care. 2020;24:522. - DOI
- Song W-C, FitzGerald GA. COVID-19, microangiopathy, hemostatic activation, and complement. J Clin Invest. 2020;130:3950–3953. - DOI
- José RJ, Williams A, Manuel A, Brown JS, Chambers RC. Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis. Eur Respir Rev. 2020;29:200240. - DOI
- Tyml K. Vitamin C and microvascular dysfunction in systemic inflammation. Antioxidants. 2017;6:49. - DOI
- Hiedra R, Lo KB, Elbashabsheh M, Gul F, Wright RM, Albano J, Azmaiparashvili Z, Aponte GP. The use of IV vitamin C for patients with COVID-19: a case series. Expert Rev Anti Infect Ther. 2020;18:1259–1261. - DOI
- Guglielmetti G, Quaglia M, Sainaghi PP, Castello LM, Vaschetto R, Pirisi M, Corte FD, Avanzi GC, Stratta P, Cantaluppi V. War to the knife” against thromboinflammation to protect endothelial function of COVID-19 patients. Crit Care. 2020;24:365. - DOI
- McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2020;2:e437–e445. - DOI
- Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013;2013:CD000980. - DOI
- Hemilä H. Vitamin C intake and susceptibility to pneumonia. Pediatr Infect Dis J. 1997;16:836–837. - DOI
- Fowler AA III, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure. JAMA. 2019;322:1261. - DOI
- Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open. 2020;10:e039519. - DOI
- Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo G, Luo G, Meng Z, Backer DD, Xiang H, Peng Z-Y. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care. 2021;11:5. - DOI
- .
- DRI dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids.. 2000. - DOI
- Gois P, Ferreira D, Olenski S, Seguro A. Vitamin D and infectious diseases: simple bystander or contributing factor?. Nutrients. 2017;9:651. - DOI
- Gruber-Bzura BM. Vitamin D and influenza—prevention or therapy?. Int J Mol Sci. 2018;19:2419. - DOI
- Charoenngam N, Holick MF. Immunologic effects of Vitamin D on human health and disease. Nutrients. 2020;12:2097. - DOI
- Hughes DA, Norton R. Vitamin D and respiratory health. Clin Exp Immunol. 2009;158:20–25. - DOI
- Vanherwegen A-S, Gysemans C, Mathieu C. Regulation of immune function by Vitamin D and its use in diseases of immunity. Endocrinol Metab Clin North Am. 2017;46:1061–1094. - DOI
- Aranow C. Vitamin D and the immune system. J Investig Med. 2015;59:881–886. - DOI
- Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol. 2013;136:321–329. - DOI
- Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010;10:482–496. - DOI
- Grant WB, Henry L, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12:988. - DOI
- Rhodes JM, Subramanian S, Laird E, Griffin G, Kenny RA. Perspective: Vitamin D deficiency and COVID‐19 severity—plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. J Intern Med. 2020;289:97–115. - DOI
- Whittemore PB. COVID-19 fatalities, latitude, sunlight, and Vitamin D. Am J Infect Control. 2020;48:1042–1044. - DOI
- Rhodes JM, Subramanian S, Laird E, Kenny RA. Low population mortality from COVID-19 in countries south of latitude 35 degrees north supports Vitamin D as a factor determining severity. Aliment Pharmacol Ther. 2020;51:1434–1437. - DOI
- D’Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, Keller F, Cantù M. 25-HydroxyVitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients. 2020;12:1359. - DOI
- De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics. 2020. - DOI
- Maghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, Tabriz HM, Hadadi A, Montazeri M, Nasiri M, Shirvani A, Holick MF. Vitamin D sufficiency, a serum 25-hydroxyVitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS One. 2020;15:e0239799. - DOI
- Ali N. Role of Vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13:1373–1380. - DOI
- Merzon E, Tworowski D, Gorohovski A, Vinker S, Golan Cohen A, Green I, Frenkel‐Morgenstern M. Low plasma 25(OH) Vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study. FEBS J. 2020;287:3693–3702. - DOI
- Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open. 2020;3:e2019722. - DOI
- Hernández JL, Nan D, Fernandez-Ayala M, García-Unzueta M, Hernández-Hernández MA, López-Hoyos M, Muñoz-Cacho P, Olmos JM, Gutiérrez-Cuadra M, Ruiz-Cubillán JJ, Crespo J, Martínez-Taboada VM. Vitamin D status in hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol Metab. 2020;106:e1343–e1353. - DOI
- Jain A, Chaurasia R, Sengar NS, Singh M, Mahor S, Narain S. Analysis of Vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep. 2020;10:20191. - DOI
- Vassiliou AG, Jahaj E, Pratikaki M, Orfanos SE, Dimopoulou I, Kotanidou A. Low 25-hydroxyVitamin D levels on admission to the intensive care unit may predispose COVID-19 pneumonia patients to a higher 28-day mortality risk: a pilot study on a Greek ICU cohort. Nutrients. 2020;12:3773. - DOI
- Carpagnano GE, Di Lecce V, Quaranta VN, Zito A, Buonamico E, Capozza E, Palumbo A, Gioia GD, Valerio VN, Resta O. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest. 2020;44:765–771. - DOI
- Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D deficiency and outcome of COVID-19 patients. Nutrients. 2020;12:2757. - DOI
- Pizzini A, Aichner M, Sahanic S, Böhm A, Egger A, Hoermann G, Kurz K, Widmann G, Bellmann-Weiler R, Weiss G, Tancevski I, Sonnweber T, Löffler-Ragg J. Impact of Vitamin D deficiency on COVID-19—a prospective analysis from the CovILD Registry. Nutrients. 2020;12:2775. - DOI
- Ye K, Tang F, Liao X, Shaw BA, Deng M, Huang G, Qin Z, Peng X, Xiao H, Chen C, Liu X, Ning L, Wang B, Tang N, Li M, Xu F, Lin S, Yang J. Does serum Vitamin D level affect COVID-19 infection and its severity?—A case-control study. J Am Coll Nutr. 2020. - DOI
- Padhi S, Suvankar S, Panda VK, Pati A, Panda AK. Lower levels of Vitamin D are associated with SARS-CoV-2 infection and mortality in the Indian population: an observational study. Int Immunopharmacol. 2020;88:107001. - DOI
- Luo X, Liao Q, Shen Y, Li H, Cheng L. Vitamin D deficiency is associated with COVID-19 incidence and disease severity in Chinese people. J Nutr. 2021;151:98–103. - DOI
- Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O'Donnell CA, Gill JM, Sattar N, Pell JP. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020;14:561–565. - DOI
- Hastie CE, Pell JP, Sattar N. Vitamin D and COVID-19 infection and mortality in UK Biobank. Eur J Nutr. 2020;60:545–548. - DOI
- Panagiotou G, Tee SA, Ihsan Y, Athar W, Marchitelli G, Kelly D, Boot CS, Stock N, Macfarlane J, Martineau AR, Burns G, Quinton R. Low serum 25‐hydroxyVitamin D (25OHD) levels in patients hospitalized with COVID‐19 are associated with greater disease severity. Clin Endocrinol. 2020;93:508–511. - DOI
- Grant WB, McDonnell SL. Letter in response to the article: Vitamin D concentrations and COVID-19 infection in UK biobank (Hastie et al.). Diabetes Metab Syndr. 2020;14:893–894. - DOI
- Giménez VMM, Inserra F, Ferder L, García J, Manucha W. Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2. J Hum Hypertens. 2020. - DOI
- Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. Evidence for possible association of Vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients. Aging Clin Exp Res. 2020;32:2141–2158. - DOI
- Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, Puri GD, Malhotra P. Short term, high-dose Vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgrad Med J. 2020. - DOI
- Entrenas Castillo M, Entrenas Costa LM, Barrios JMV, Alcalá Díaz JF, Miranda JL, Bouillon R, Gomez JMQ. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: a pilot randomized clinical study. J Steroid Biochem Mol Biol. 2020;203:105751. - DOI
- Jungreis I, Kellis M. Mathematical analysis of Córdoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients. 2020.
- Ling SF, Broad E, Murphy R, Pappachan JM, Pardesi-Newton S, Kong M-F, Jude EB. High-dose cholecalciferol booster therapy is associated with a reduced risk of mortality in patients with COVID-19: a cross-sectional multi-centre observational study. Nutrients. 2020;12:3799. - DOI
- Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Reis BZ, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of Vitamin D3 supplementation vs placebo on hospital length of stay in patients with severe COVID-19: a multicenter, double-blind, randomized controlled trial. 2020.
- Castillo Garzón M. Vitamin D on prevention and treatment of COVID-19 (COVITD-19). 2020.
- Montano-Loza A. Vitamin D and COVID-19 management. 2020.
- Cholecalciferol to improve the outcomes of COVID-19 patients. 2020.
- COvid-19 and Vitamin D supplementation: a multicenter randomized controlled trial of high dose versus standard dose Vitamin D3 in high-risk COVID-19 patients (CoVitTrial). 2020.
- The LEAD COVID-19 Trial: low-risk, early aspirin and Vitamin D to reduce COVID-19 hospitalizations (LEAD COVID-19). 2020.
- McCreary M. Randomized proof-of-concept trial to evaluate the safety and explore the effectiveness of resveratrol, a plant polyphenol, for COVID-19. 2020.
- Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, Stepan J, El-Hajj Fuleihan G, Bouillon R. Current Vitamin D status in European and Middle East countries and strategies to prevent Vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol. 2019;180:P23–P54. - DOI
- Communiqué de l’Académie nationale de Médecine: vitamine D et Covid-19.
- Iacobucci G. Covid-19: NHS bosses told to assess risk to ethnic minority staff who may be at greater risk. BMJ. 2020;369:m1820. - DOI
- Ingrid T. Covid-19: public health agencies review whether Vitamin D supplements could reduce risk. BMJ. 2020;369:m2475. - DOI
- Kohlmeier M. Avoidance of Vitamin D deficiency to slow the COVID-19 pandemic. BMJ Nutr Prev Health. 2020;3:67–73. - DOI
- COVID-19 rapid guideline: Vitamin D. 2020.
- Parva NR, Tadepalli S, Singh P, Qian A, Joshi R, Kandala H, Nookala VK, Cheriyath P. Prevalence of Vitamin D deficiency and associated risk factors in the US population (2011–2012). Cureus. 2018;10:e2741. - DOI
- COVID-19 treatment guidelines. Vitamin D. 2020.
- Hamulka J, Jeruszka-Bielak M, Górnicka M, Drywień ME, Zielinska-Pukos MA. Dietary supplements during COVID-19 outbreak. Results of Google Trends analysis supported by PLifeCOVID-19 Online Studies. Nutrients. 2020;13:54. - DOI
- Court orders Georgia defendants to stop selling Vitamin D products as treatments for Covid-19 and other diseases. 2021.
- Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–514. - DOI
- Kang E-J, Kim SY, Hwang I-H, Ji Y-J. The effect of probiotics on prevention of common cold: a meta-analysis of randomized controlled trial studies. Korean J Fam Med. 2013;34:2. - DOI
- Osamu K, Akira A, Sazaly A, Naoki Y. Probiotics and paraprobiotics in viral infection: clinical application and effects on the innate and acquired immune systems. Curr Pharm Des. 2018;24:710–717. - DOI
- Baud D, Agri VD, Gibson GR, Reid G, Giannoni E. Using probiotics to flatten the curve of coronavirus disease COVID-2019 pandemic. Front Public Health. 2020;8:00186. - DOI
- O’Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat Microbiol. 2017;2:17057. - DOI
- Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of action of probiotics. Adv Nutr. 2019;10:S49–S66. - DOI
- Halloran K, Underwood MA. Probiotic mechanisms of action. Early Hum Dev. 2019;135:58–65. - DOI
- Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012;61:160–174. - DOI
- Botic T, Klingberg T, Weingartl H, Cencic A. A novel eukaryotic cell culture model to study antiviral activity of potential probiotic bacteria. Int J Food Microbiol. 2007;115:227–234. - DOI
- Waki N, Yajima N, Suganuma H, Buddle BM, Luo D, Heiser A, Zheng T. Oral administration of Lactobacillus brevis KB290 to mice alleviates clinical symptoms following influenza virus infection. Lett Appl Microbiol. 2014;58:87–93. - DOI
- Mastromarino P, Cacciotti F, Masci A, Mosca L. Antiviral activity of Lactobacillus brevis towards herpes simplex virus type 2: role of cell wall associated components. Anaerobe. 2011;17:334–336. - DOI
- Percopo CM, Michelle M, Brenner TA, Krumholz JO, Break TJ, Karen L, Rosenberg HF. Critical adverse impact of IL-6 in acute pneumovirus infection. J Immunol. 2019;202:871–882. - DOI
- Biliavska L, Pankivska Y, Povnitsa O, Zagorodnya S. Antiviral activity of exopolysaccharides produced by lactic acid bacteria of the genera Pediococcus, Leuconostoc and Lactobacillus against human adenovirus type 5. Medicina. 2019;55:519. - DOI
- Eguchi K, Fujitani N, Nakagawa H, Miyazaki T. Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055. Sci Rep. 2019;9:4812. - DOI
- Turner RB, Woodfolk JA, Borish L, Steinke JW, Patrie JT, Muehling LM, Lahtinen S, Lehtinen MJ. Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection—a randomised controlled trial. Benef Microbes. 2017;8:207–215. - DOI
- Zelaya H, Tsukida K, Chiba E, Marranzino G, Alvarez S, Kitazawa H, Agüero G, Villena J. Immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation–coagulation interactions. Int Immunopharmacol. 2014;19:161–173. - DOI
- Tonetti FR, Islam MA, Vizoso-Pinto MG, Takahashi H, Kitazawa H, Villena J. Nasal priming with immunobiotic lactobacilli improves the adaptive immune response against influenza virus. Int Immunopharmacol. 2020;78:106115. - DOI
- Olaimat AN, Aolymat I, Al-Holy M, Ayyash M, Abu Ghoush M, Al-Nabulsi AA, Osaili T, Apostolopoulos V, Liu S-Q, Shah NP. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. NPJ Sci Food. 2020;4:17. - DOI
- Keely S, Talley NJ, Hansbro PM. Pulmonary-intestinal cross-talk in mucosal inflammatory disease. Mucosal Immunol. 2011;5:7–18. - DOI
- Dumas A, Bernard L, Poquet Y, Lugo-Villarino G, Neyrolles O. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol. 2018;20:e12966. - DOI
- Dhar D, Mohanty A. Gut microbiota and Covid-19—possible link and implications. Virus Res. 2020;285:198018. - DOI
- Bao L, Zhang C, Dong J, Zhao L, Li Y, Sun J. Oral microbiome and SARS-CoV-2: beware of lung co-infection. Front Microbiol. 2020;11:1840. - DOI
- Khatiwada S, Subedi A. Lung microbiome and coronavirus disease 2019 (COVID-19): possible link and implications. Hum Microb J. 2020;17:100073. - DOI
- Lehtoranta L, Pitkäranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014;33:1289–1302. - DOI
- Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;2:1465–1858. - DOI
- Vouloumanou EK, Makris GC, Karageorgopoulos DE, Falagas ME. Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrobial Agents. 2009;34:197.e1–197.e10. - DOI
- King S, Glanville J, Sanders ME, Fitzgerald A, Varley D. Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis. Br J Nutr. 2014;112:41–54. - DOI
- Zeng J, Wang C-T, Zhang F-S, Qi F, Wang S-F, Ma S, Wu T-J, Tian H, Tian Z-T, Zhang S-L, Qu Y, Liu L-Y, Li Y-Z, Cui S, Zhao H-L, Du Q-S, Ma Z, Li C-H, Li Y, Si M, Chu Y-F, Meng M, Ren H-S, Zhang J-C, Jiang J-J, Ding M, Wang Y-P. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med. 2016;42:1018–1028. - DOI
- Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2010;182:1058–1064. - DOI
- Shimizu K, Yamada T, Ogura H, Mohri T, Kiguchi T, Fujimi S, Asahara T, Yamada T, Ojima M, Ikeda M, Shimazu T. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial. Crit Care. 2018;22:239. - DOI
- Su M, Jia Y, Li Y, Zhou D, Jia J. Probiotics for the prevention of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Respir Care. 2020;65:673–685. - DOI
- Póvoa HCC, Chianca GC, Iorio NLPP. COVID-19: an alert to ventilator-associated bacterial pneumonia. Infect Dis Ther. 2020;9:417–420. - DOI
- François B, Laterre P-F, Luyt C-E, Chastre J. The challenge of ventilator-associated pneumonia diagnosis in COVID-19 patients. Crit Care. 2020;24:289. - DOI
- Perceval C, Szajewska H, Indrio F, Weizman Z, Vandenplas Y. Prophylactic use of probiotics for gastrointestinal disorders in children. Lancet Child Adolesc Health. 2019;3:655–662. - DOI
- Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Effect of gastrointestinal symptoms in patients with COVID-19. Gastroenterology. 2020;158:2294–2297. - DOI
- Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, Cui X, Xiao J, Meng T, Zhou W, Liu J, Xu H. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. 2020.
- Miao G, Wenfei S, Haixia Z, Jingwei X, Silian C, Ye X, Xinquan W. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 2016;27:119–129. - DOI
- Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, Yin H, Xiao Q, Tang Y, Qu X, Kuang L, Fang X, Mishra N, Lu J, Shan H, Jiang G, Huang X. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. 2020;5:434–435. - DOI
- Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831–1833.e3. - DOI
- Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible?. Lancet Gastroenterol Hepatol. 2020;5:335–337. - DOI
- Xu Y, Li X, Zhu B, Liang H, Fang C, Gong Y, Guo Q, Sun X, Zhao D, Shen J, Zhang H, Liu H, Xia H, Tang J, Zhang K, Gong S. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26:502–505. - DOI
- Gonzalez-Ochoa G, Flores-Mendoza LK, Icedo-Garcia R, Gomez-Flores R, Tamez-Guerra P. Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics. Arch Microbiol. 2017;199:953–961. - DOI
- Freedman SB, Williamson-Urquhart S, Farion KJ, Gouin S, Willan AR, Poonai N, Hurley K, Sherman PM, Finkelstein Y, Lee BE, Pang X-L, Chui L, Schnadower D, Xie J, Gorelick M, Schuh S. Multicenter trial of a combination probiotic for children with gastroenteritis. N Engl J Med. 2018;379:2015–2026. - DOI
- Synbiotic therapy of gastrointestinal symptoms during Covid-19 infection (SynCov). 2021.
- Evaluation of the probiotic Lactobacillus coryniformis K8 on COVID-19 prevention in healthcare workers. 2020.
- Bioithas SL. The intestinal microbiota as a therapeutic target in hospitalized patients with COVID-19 infection. 2021.
- Gregor R. Probiotics: definition, scope and mechanisms of action. Best Pract Res Clin Gastroenterol. 2016;30:17–25. - DOI
- Rijkers GT, de Vos WM, Brummer R-J, Morelli L, Corthier G, Marteau P. Health benefits and health claims of probiotics: bridging science and marketing. Br J Nutr. 2011;106:1291–1296. - DOI
- Mak JW, Chan FK, Ng SC. Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol. 2020;5:644–645. - DOI
- Gao QY, Chen YX, Fang JY. 2019 Novel coronavirus infection and gastrointestinal tract. J Dig Dis. 2020;21:125–126. - DOI
- Probiotics market worth $76.7 billion by 2027—exclusive report covering pre and post COVID-19 market analysis by Meticulous. 2020.
- Marcos P, Alialdo DD, Azevedo LMG, de Almeida Oliveira T, da Mota Santana J. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020. - DOI
- Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383:2255–2273. - DOI
- Galland L. Diet and Inflammation. Nutr Clin Pract. 2010;25:634–640. - DOI
- Kain V, Van Der Pol W, Mariappan N, Ahmad A, Eipers P, Gibson DL, Gladine C, Vigor C, Durand T, Morrow C, Halade GV. Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophi:lymphocyte ratio, leading to inflamed milieu in acute heart failure. FASEB J. 2019;33:6456–6469. - DOI
- Colloidal silver. 2017.
- Yadi Z, Hou Y, Jiayu S, Yin H, William M, Feixiong C. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:14. - DOI
- Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ. Role of melatonin on virus-induced neuropathogenesis—a concomitant therapeutic strategy to understand SARS-CoV-2 infection. Antioxidants. 2021;10:47. - DOI
- McCarty MF, Iloki Assanga SB, Lewis Luján L, O’Keefe JH, DiNicolantonio JJ. Nutraceutical strategies for suppressing NLRP3 inflammasome activation: pertinence to the management of COVID-19 and beyond. Nutrients. 2020;13:47. - DOI
- Cohen J. Update: here’s what is known about Trump’s COVID-19 treatment. Science. 2020;372:abf0974. - DOI
- Panayiotis L, Benjamin M, Kerstin K, Graham MS, Mazidi M, Leeming ER, Thompson E, Bowyer R, Drew DA, Nguyen LH, Merino J, Gomez M, Mompeo O, Costeira R, Sudre CH, Gibson R, Steves CJ, Wolf J, Franks PW, Ourselin S, Chan AT, Berry SE, Valdes AM, Calder PC, Spector TD, Menni C. Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID Symptom Study app—a longitudinal app-based community survey. 2020.
- Barazzoni R, Bischoff SC, Breda J, Wickramasinghe K, Krznaric Z, Nitzan D, Pirlich M, Singer P. ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection. Clin Nutr. 2020;39:1631–1638. - DOI
- Haraj NE, El Aziz S, Chadli A, Dafir A, Mjabber A, Aissaoui O, Barrou L, El Kettani El Hamidi C, Nsiri A, Al Harrar R, Ezzouine H, Charra B, Abdallaoui MS, El Kebbaj N, Kamal N, Bennouna GM, El Filali KM, Ramdani B, El Mdaghri N, Gharbi MB, Afif MH. Nutritional status assessment in patients with Covid-19 after discharge from the intensive care unit. Clin Nutr ESPEN. 2021;41:423–428. - DOI
- Berger MM. Nutrition status affects COVID‐19 patient outcomes. JPEN J Parenter Enteral Nutr. 2020;44:1166–1167. - DOI
- Zhao X, Li Y, Ge Y, Shi Y, Lv P, Zhang J, Fu G, Zhou Y, Jiang K, Lin N, Bai T, Jin R, Wu Y, Yang X, Li X. Evaluation of nutrition risk and its association with mortality risk in severely and critically ill COVID‐19 patients. JPEN J Parenter Enteral Nutr. 2020;45:32–42. - DOI
- Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, Acosta S, Naqvi R, Burmeister-Morton F, Burmeister F, Tarriela A, Petershack M, Evans M, Hoang A, Rajasekaran K, Ahuja S, Moreira A. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine. 2020;26:100527. - DOI
- Brugliera L, Spina A, Castellazzi P, Cimino P, Arcuri P, Negro A, Houdayer E, Alemanno F, Giordani A, Mortini P, Iannaccone S. Nutritional management of COVID-19 patients in a rehabilitation unit. Eur J Clin Nutr. 2020;74:860–863. - DOI
- Laura DD, Virginia F-R, Montaña C. The frontier between nutrition and pharma: the international regulatory framework of functional foods, food supplements and nutraceuticals. Crit Rev Food Sci Nutr. 2019;60:1738–1746. - DOI
- Coronavirus update: FDA and FTC warn seven companies selling fraudulent products that claim to treat or prevent COVID-19. 2020.
- Park SW, Sun K, Viboud C, Grenfell BT, Dushoff J. Potential roles of social distancing in mitigating the spread of coronavirus disease 2019 (COVID-19) in South Korea. 2020.
- Matrajt L, Leung T. Evaluating the effectiveness of social distancing interventions to delay or flatten the epidemic curve of coronavirus disease. Emerg Infect Dis. 2020;26:1740–1748. - DOI