Does Prophylactic Oral Zinc Reduce the Risk of Contracting COVID-19?
Sean D Adrean, Kenneth Schmitt, Caleb Ng, Ash Pirouz, Hema L Ramkumar, Scott Grant
Cureus, doi:10.7759/cureus.30881
In this study, we aimed to investigate whether zinc provided in Age-Related Eye Disease Study 2 (AREDS2) vitamins is associated with a decreased risk of contracting coronavirus disease 2019 . 
 Materials and methods We conducted a retrospective observational cohort study involving patients at a retina-only practice who were provided a questionnaire at each visit to assess whether they were symptomatic of or had contracted COVID-19. Those who answered yes to testing positive for COVID-19 were retrospectively analyzed and categorized based on their AREDS2 vitamin use, and a Pearson's chi-squared test was performed. Demographic data and past ocular history were also analyzed. 
 Results A total of 8,426 unique patients, including 2,111 with a diagnosis of age-related macular degeneration (AMD), were seen from April 1, 2020, to April 9, 2021. A total of 110 patients (1.3%) reported contracting COVID-19 and had positive COVID-19 tests. The average age of those who had contracted COVID-19 in this study was 68.3 years; 51.8% were male, 30.1% had AMD, 28.2% had diabetic retinopathy, 24.5% had surgical retinal disease, 11.8% had retinal vascular disease, and 4.5% had other disease states. Of the COVID-19positive patients, 27.3% (30/110) took AREDS2 vitamins, while 72.7% (80/110) patients did not. A chisquared analysis was performed, which was not statistically significant (p=0.667). 
 Conclusions Oral zinc supplementation, in the form of AREDS2 vitamins, is not associated with a protective effect against contracting COVID-19.
Conclusions Oral zinc supplementation has been widely purported to reduce symptomatic viral days. It has also been recommended to be used as a prophylaxis for viral infections. It has been speculated that it may help reduce the chance of contracting COVID-19. Zinc is readily available over the counter and is used in the AREDS supplements for macular degeneration. Elderly patients are at increased risk of complications from COVID-19, and hence if zinc supplementation could reduce the chance of contracting COVID-19, that would be highly beneficial. However, based on our findings, oral zinc supplementation in the form of AREDS2 vitamins is not associated with a protective effect against contracting COVID-19.   
 Appendices
References
Voysey, Clemens, Madhi, Safety and efficacy of the ChAdOx1 nCoV-19 vaccine
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    {
      "DOI": "10.1038/s41579-020-00468-6",
      "article-title": "Coronavirus biology and replication: implications for SARS-CoV-2",
      "author": "V'kovski P",
      "doi-asserted-by": "publisher",
      "journal-title": "Nat Rev Microbiol",
      "key": "ref1",
      "unstructured": "V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021, 19:155-70. 10.1038/s41579-020-00468-6",
      "volume": "19",
      "year": "2021"
    },
    {
      "DOI": "10.14218/JCTH.2020.00018",
      "article-title": "COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies",
      "author": "Feng G",
      "doi-asserted-by": "publisher",
      "journal-title": "J Clin Transl Hepatol",
      "key": "ref2",
      "unstructured": "Feng G, Zheng KI, Yan QQ, et al.. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J Clin Transl Hepatol. 2020, 8:18-24. 10.14218/JCTH.2020.00018",
      "volume": "8",
      "year": "2020"
    },
    {
      "DOI": "10.1056/NEJMoa200776",
      "article-title": "Remdesivir for the treatment of COVID-19 - preliminary report",
      "author": "McMahon JH",
      "doi-asserted-by": "publisher",
      "journal-title": "N Engl J Med",
      "key": "ref3",
      "unstructured": "McMahon JH, Udy A, Peleg AY. Remdesivir for the treatment of COVID-19 - preliminary report. N Engl J Med. 2020, 383:992-3. 10.1056/NEJMoa200776",
      "volume": "383",
      "year": "2020"
    },
    {
      "DOI": "10.1056/NEJMoa2021436",
      "article-title": "Dexamethasone in hospitalized patients with Covid-19",
      "author": "Horby P",
      "doi-asserted-by": "publisher",
      "journal-title": "N Engl J Med",
      "key": "ref4",
      "unstructured": "Horby P, Lim WS, Emberson JR, et al.. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021, 384:693-704. 10.1056/NEJMoa2021436",
      "volume": "384",
      "year": "2021"
    },
    {
      "DOI": "10.1056/NEJMp2032369",
      "article-title": "FDA approval of remdesivir - a step in the right direction",
      "author": "Rubin D",
      "doi-asserted-by": "publisher",
      "journal-title": "N Engl J Med",
      "key": "ref5",
      "unstructured": "Rubin D, Chan-Tack K, Farley J, Sherwat A. FDA approval of remdesivir - a step in the right direction. N Engl J Med. 2020, 383:2598-600. 10.1056/NEJMp2032369",
      "volume": "383",
      "year": "2020"
    },
    {
      "DOI": "10.1056/NEJMoa2101544",
      "article-title": "Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19",
      "author": "Sadoff J",
      "doi-asserted-by": "publisher",
      "journal-title": "N Engl J Med",
      "key": "ref6",
      "unstructured": "Sadoff J, Gray G, Vandebosch A, et al.. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021, 384:2187-201. 10.1056/NEJMoa2101544",
      "volume": "384",
      "year": "2021"
    },
    {
      "DOI": "10.1016/S0140-6736(20)32661-1",
      "article-title": "Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK",
      "author": "Voysey M",
      "doi-asserted-by": "publisher",
      "journal-title": "Lancet",
      "key": "ref7",
      "unstructured": "Voysey M, Clemens SA, Madhi SA, et al.. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021, 397:99-111. 10.1016/S0140-6736(20)32661-1",
      "volume": "397",
      "year": "2021"
    },
    {
      "DOI": "10.1056/NEJMoa2108891",
      "article-title": "Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant",
      "author": "Lopez Bernal J",
      "doi-asserted-by": "publisher",
      "journal-title": "N Engl J Med",
      "key": "ref8",
      "unstructured": "Lopez Bernal J, Andrews N, Gower C, et al.. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N Engl J Med. 2021, 385:585-94. 10.1056/NEJMoa2108891",
      "volume": "385",
      "year": "2021"
    },
    {
      "DOI": "10.1007/s12011-020-02437-9",
      "article-title": "Zinc and COVID-19: basis of current clinical trials",
      "author": "Pal A",
      "doi-asserted-by": "publisher",
      "journal-title": "Biol Trace Elem Res",
      "key": "ref9",
      "unstructured": "Pal A, Squitti R, Picozza M, et al.. Zinc and COVID-19: basis of current clinical trials. Biol Trace Elem Res. 2021, 199:2882-92. 10.1007/s12011-020-02437-9",
      "volume": "199",
      "year": "2021"
    },
    {
      "DOI": "10.1016/j.abb.2016.03.022",
      "article-title": "Zinc and immunity: an essential interrelation",
      "author": "Maares M",
      "doi-asserted-by": "publisher",
      "journal-title": "Arch Biochem Biophys",
      "key": "ref10",
      "unstructured": "Maares M, Haase H. Zinc and immunity: an essential interrelation. Arch Biochem Biophys. 2016, 611:58-65. 10.1016/j.abb.2016.03.022",
      "volume": "611",
      "year": "2016"
    },
    {
      "DOI": "10.3945/an.112.003038",
      "article-title": "Zinc biochemistry: from a single zinc enzyme to a key element of life",
      "author": "Maret W",
      "doi-asserted-by": "publisher",
      "journal-title": "Adv Nutr",
      "key": "ref11",
      "unstructured": "Maret W. Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr. 2013, 4:82-91. 10.3945/an.112.003038",
      "volume": "4",
      "year": "2013"
    },
    {
      "DOI": "10.1007/s00775-011-0797-4",
      "article-title": "Zinc homeostasis and signaling in health and diseases: zinc signaling",
      "author": "Fukada T",
      "doi-asserted-by": "publisher",
      "journal-title": "J Biol Inorg Chem",
      "key": "ref12",
      "unstructured": "Fukada T, Yamasaki S, Nishida K, Murakami M, Hirano T. Zinc homeostasis and signaling in health and diseases: zinc signaling. J Biol Inorg Chem. 2011, 16:1123-34. 10.1007/s00775-011-0797-4",
      "volume": "16",
      "year": "2011"
    },
    {
      "DOI": "10.1177/0148607115572193",
      "article-title": "Safety and dose escalation study of intravenous zinc supplementation in pediatric critical illness",
      "author": "Cvijanovich NZ",
      "doi-asserted-by": "publisher",
      "journal-title": "JPEN J Parenter Enteral Nutr",
      "key": "ref13",
      "unstructured": "Cvijanovich NZ, King JC, Flori HR, Gildengorin G, Vinks AA, Wong HR. Safety and dose escalation study of intravenous zinc supplementation in pediatric critical illness. JPEN J Parenter Enteral Nutr. 2016, 40:860-8. 10.1177/0148607115572193",
      "volume": "40",
      "year": "2016"
    },
    {
      "DOI": "10.1331/1544-3191.44.5.594.hulisz",
      "article-title": "Efficacy of zinc against common cold viruses: an overview",
      "author": "Hulisz D",
      "doi-asserted-by": "publisher",
      "journal-title": "J Am Pharm Assoc (2003)",
      "key": "ref14",
      "unstructured": "Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003). 2004, 44:594-603. 10.1331/1544-3191.44.5.594.hulisz",
      "volume": "44",
      "year": "2004"
    },
    {
      "DOI": "10.1128/AAC.48.3.783-790.2004",
      "article-title": "Effect of zinc salts on respiratory syncytial virus replication",
      "author": "Suara RO",
      "doi-asserted-by": "publisher",
      "journal-title": "Antimicrob Agents Chemother",
      "key": "ref15",
      "unstructured": "Suara RO, Crowe JE Jr. Effect of zinc salts on respiratory syncytial virus replication. Antimicrob Agents Chemother. 2004, 48:783-90. 10.1128/AAC.48.3.783-790.2004",
      "volume": "48",
      "year": "2004"
    },
    {
      "DOI": "10.1371/journal.ppat.1001176",
      "article-title": "Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture",
      "author": "te Velthuis AJ",
      "doi-asserted-by": "publisher",
      "journal-title": "PLoS Pathog",
      "key": "ref16",
      "unstructured": "te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) 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. 10.1371/journal.ppat.1001176",
      "volume": "6",
      "year": "2010"
    },
    {
      "DOI": "10.1093/advances/nmz013",
      "article-title": "The role of zinc in antiviral immunity",
      "author": "Read SA",
      "doi-asserted-by": "publisher",
      "journal-title": "Adv Nutr",
      "key": "ref17",
      "unstructured": "Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Adv Nutr. 2019, 10:696-710. 10.1093/advances/nmz013",
      "volume": "10",
      "year": "2019"
    },
    {
      "DOI": "10.3945/an.116.013177",
      "article-title": "The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration",
      "author": "Gorusupudi A",
      "doi-asserted-by": "publisher",
      "journal-title": "Adv Nutr",
      "key": "ref18",
      "unstructured": "Gorusupudi A, Nelson K, Bernstein PS. The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration. Adv Nutr. 2017, 8:40-53. 10.3945/an.116.013177",
      "volume": "8",
      "year": "2017"
    },
    {
      "DOI": "10.1016/j.ajo.2020.04.028",
      "article-title": "Investigate oral zinc as a prophylactic treatment for those at risk for COVID-19",
      "author": "McPherson SW",
      "doi-asserted-by": "publisher",
      "journal-title": "Am J Ophthalmol",
      "key": "ref19",
      "unstructured": "McPherson SW, Keunen JE, Bird AC, Chew EY, van Kuijk FJ. Investigate oral zinc as a prophylactic treatment for those at risk for COVID-19. Am J Ophthalmol. 2020, 216:A5-6. 10.1016/j.ajo.2020.04.028",
      "volume": "216",
      "year": "2020"
    },
    {
      "DOI": "10.1001/archopht.119.10.1417",
      "article-title": "A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8",
      "author": "Age-Related Eye Disease Study Research Group",
      "doi-asserted-by": "publisher",
      "journal-title": "Arch Ophthalmol",
      "key": "ref20",
      "unstructured": "Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001, 119:1417-36. 10.1001/archopht.119.10.1417",
      "volume": "119",
      "year": "2001"
    },
    {
      "DOI": "10.1038/nature02145",
      "article-title": "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus",
      "author": "Li W",
      "doi-asserted-by": "publisher",
      "journal-title": "Nature",
      "key": "ref21",
      "unstructured": "Li W, Moore MJ, Vasilieva N, et al.. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003, 426:450-4. 10.1038/nature02145",
      "volume": "426",
      "year": "2003"
    },
    {
      "DOI": "10.1136/bmjopen-2020-047474",
      "article-title": "Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials",
      "author": "Hunter J",
      "doi-asserted-by": "publisher",
      "journal-title": "BMJ Open",
      "key": "ref22",
      "unstructured": "Hunter J, Arentz S, Goldenberg J, et al.. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021, 11:e047474. 10.1136/bmjopen-2020-047474",
      "volume": "11",
      "year": "2021"
    },
    {
      "DOI": "10.1016/j.chest.2020.06.082",
      "article-title": "The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study",
      "author": "Yao JS",
      "doi-asserted-by": "publisher",
      "journal-title": "Chest",
      "key": "ref23",
      "unstructured": "Yao JS, Paguio JA, Dee EC, et al.. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest. 2021, 159:108-11. 10.1016/j.chest.2020.06.082",
      "volume": "159",
      "year": "2021"
    },
    {
      "DOI": "10.1001/jamanetworkopen.2021.0369",
      "article-title": "Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients with SARS-CoV-2 infection: the COVID A to Z randomized clinical trial",
      "author": "Thomas S",
      "doi-asserted-by": "publisher",
      "journal-title": "JAMA Netw Open",
      "key": "ref24",
      "unstructured": "Thomas S, Patel D, Bittel B, et al.. Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients with SARS-CoV-2 infection: the COVID A to Z randomized clinical trial. JAMA Netw Open. 2021, 4:e210369. 10.1001/jamanetworkopen.2021.0369",
      "volume": "4",
      "year": "2021"
    },
    {
      "DOI": "10.1111/bcp.14826",
      "article-title": "Zinc supplementation as an adjunct therapy for COVID-19: challenges and opportunities",
      "author": "Chinni V",
      "doi-asserted-by": "publisher",
      "journal-title": "Br J Clin Pharmacol",
      "key": "ref25",
      "unstructured": "Chinni V, El-Khoury J, Perera M, et al.. Zinc supplementation as an adjunct therapy for COVID-19: challenges and opportunities. Br J Clin Pharmacol. 2021, 87:3737-46. 10.1111/bcp.14826",
      "volume": "87",
      "year": "2021"
    },
    {
      "DOI": "10.3945/ajcn.2010.28674I",
      "article-title": "Zinc bioavailability and homeostasis",
      "author": "Hambidge KM",
      "doi-asserted-by": "publisher",
      "journal-title": "Am J Clin Nutr",
      "key": "ref26",
      "unstructured": "Hambidge KM, Miller LV, Westcott JE, Sheng X, Krebs NF. Zinc bioavailability and homeostasis. Am J Clin Nutr. 2010, 91:1478S-83S. 10.3945/ajcn.2010.28674I",
      "volume": "91",
      "year": "2010"
    },
    {
      "DOI": "10.3390/nu12030762",
      "article-title": "A guide to human zinc absorption: general overview and recent advances of in vitro intestinal models",
      "author": "Maares M",
      "doi-asserted-by": "publisher",
      "journal-title": "Nutrients",
      "key": "ref27",
      "unstructured": "Maares M, Haase H. A guide to human zinc absorption: general overview and recent advances of in vitro intestinal models. Nutrients. 2020, 12:762. 10.3390/nu12030762",
      "volume": "12",
      "year": "2020"
    },
    {
      "DOI": "10.1080/00325481.2020.1786964",
      "article-title": "COVID-19 and comorbidities: a systematic review and meta-analysis",
      "author": "Gold MS",
      "doi-asserted-by": "publisher",
      "journal-title": "Postgrad Med",
      "key": "ref28",
      "unstructured": "Gold MS, Sehayek D, Gabrielli S, Zhang X, McCusker C, Ben-Shoshan M. COVID-19 and comorbidities: a systematic review and meta-analysis. Postgrad Med. 2020, 132:749-55. 10.1080/00325481.2020.1786964",
      "volume": "132",
      "year": "2020"
    },
    {
      "DOI": "10.1007/s15010-020-01509-1",
      "article-title": "Risk factors for Covid-19 severity and fatality: a structured literature review",
      "author": "Wolff D",
      "doi-asserted-by": "publisher",
      "journal-title": "Infection",
      "key": "ref29",
      "unstructured": "Wolff D, Nee S, Hickey NS, Marschollek M. Risk factors for Covid-19 severity and fatality: a structured literature review. Infection. 2021, 49:15-28. 10.1007/s15010-020-01509-1",
      "volume": "49",
      "year": "2021"
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