Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial

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Does zinc supplementation enhance the clinical ' "efficacy of chloroquine/hydroxychloroquine to win today's battle against " 'COVID-19?. Med Hypotheses. 2020, 142:109815. 10.1016/j.mehy.2020.109815', 'journal-title': 'Med Hypotheses'}, { 'key': 'ref2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.106214', 'article-title': 'COVID-19 outpatients: early risk-stratified treatment with zinc plus ' 'low-dose hydroxychloroquine and azithromycin: a retrospective case ' 'series study', 'volume': '56', 'author': 'Derwand R', 'year': '2020', 'unstructured': 'Derwand R, Scholz M, Zelenko V. COVID-19 outpatients: early ' 'risk-stratified treatment with zinc plus low-dose hydroxychloroquine and ' 'azithromycin: a retrospective case series study. Int J Antimicrob ' 'Agents. 2020, 56:106214. 10.1016/j.ijantimicag.2020.106214', 'journal-title': 'Int J Antimicrob Agents'}, { 'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.7150/ijbs.45498', 'article-title': 'Targeting the endocytic pathway and autophagy process as a novel ' 'therapeutic strategy in COVID-19', 'volume': '16', 'author': 'Yang N', 'year': '2020', 'unstructured': 'Yang N, Shen HM. Targeting the endocytic pathway and autophagy process ' 'as a novel therapeutic strategy in COVID-19. Int J Biol Sci. 2020, ' '16:1724-31. 10.7150/ijbs.45498', 'journal-title': 'Int J Biol Sci'}, { 'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41565-020-0674-9', 'article-title': 'Insights from nanomedicine into chloroquine efficacy against COVID-19', 'volume': '15', 'author': 'Hu TY', 'year': '2020', 'unstructured': 'Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine ' 'efficacy against COVID-19. Nat Nanotechnol. 2020, 15:247-9. ' '10.1038/s41565-020-0674-9', 'journal-title': 'Nat Nanotechnol'}, { 'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.105949', 'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results ' 'of an open-label non-randomized clinical trial', 'volume': '56', 'author': 'Gautret P', 'year': '2020', 'unstructured': 'Gautret P, Lagier JC, Parola P, et al.. Hydroxychloroquine and ' 'azithromycin as a treatment of COVID-19: results of an open-label ' 'non-randomized clinical trial. Int J Antimicrob Agents. 2020, 56:105949. ' '10.1016/j.ijantimicag.2020.105949', 'journal-title': 'Int J Antimicrob Agents'}, { 'key': 'ref6', 'unstructured': 'HCQ for COVID- 19. real-time meta analysis of 294 studies. (2021). ' 'https://hcqmeta.com/.'}, { 'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.4172/1948-5964.1000173', 'article-title': 'Azithromycin inhibits the replication of Zika virus', 'volume': '10', 'author': 'Bosseboeuf E', 'year': '2018', 'unstructured': 'Bosseboeuf E, Aubry M, Nhan T, de Pina JJ, Rolain JM, Raoult D, Musso D. ' 'Azithromycin inhibits the replication of Zika virus. J Antivir ' 'Antiretrovir. 2018, 10:6-11. 10.4172/1948-5964.1000173', 'journal-title': 'J Antivir Antiretrovir'}, { 'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.1073/pnas.1618029113/-/DCSupplemental', 'article-title': 'Zika virus cell tropism in the developing human brain and inhibition by ' 'azithromycin', 'volume': '113', 'author': 'Retallack H', 'year': '2016', 'unstructured': 'Retallack H, Di Lullo E, Arias C, et al.. Zika virus cell tropism in the ' 'developing human brain and inhibition by azithromycin. PNAS. 2016, ' '113:14408-13. 10.1073/pnas.1618029113/-/DCSupplemental', 'journal-title': 'PNAS'}, { 'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.micpath.2020.104228', 'article-title': 'In vitro testing of combined hydroxychloroquine and azithromycin on ' 'SARS-CoV-2 shows synergistic effect', 'volume': '145', 'author': 'Andreani J', 'year': '2020', 'unstructured': 'Andreani J, Le Bideau M, Duflot I, et al.. In vitro testing of combined ' 'hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic ' 'effect. Microb Pathog. 2020, 145:104228. 10.1016/j.micpath.2020.104228', 'journal-title': 'Microb Pathog'}, { 'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.3906/sag-2005-82', 'article-title': 'Hydroxychloroquine plus azithromycin and early hospital admission are ' 'beneficial in COVID-19 patients: Turkish experience with real-life data', 'volume': '51', 'author': 'Tanriverdİ E', 'year': '2021', 'unstructured': 'Tanriverdİ E, Çörtük M, Yildirim BZ, et al.. Hydroxychloroquine plus ' 'azithromycin and early hospital admission are beneficial in COVID-19 ' 'patients: Turkish experience with real-life data. Turk J Med Sci. 2021, ' '51:10-5. 10.3906/sag-2005-82', 'journal-title': 'Turk J Med Sci'}, { 'key': 'ref11', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0109180', 'article-title': 'Chloroquine is a zinc ionophore', 'volume': '9', 'author': 'Xue J', 'year': '2014', 'unstructured': 'Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a ' 'zinc ionophore. PLoS One. 2014, 9:e109180. 10.1371/journal.pone.0109180', 'journal-title': 'PLoS One'}, { 'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/advances/nmz013', 'article-title': 'The role of zinc in antiviral immunity', 'volume': '10', 'author': 'Read SA', 'year': '2019', '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', 'journal-title': 'Adv Nutr'}, { 'key': 'ref13', 'doi-asserted-by': 'publisher', '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', 'volume': '6', 'author': 'te Velthuis AJ', 'year': '2010', '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', 'journal-title': 'PLoS Pathog'}, { 'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2020.574029', 'article-title': 'The long history of vitamin C: from prevention of the common cold to ' 'potential aid in the treatment of COVID-19', 'volume': '11', 'author': 'Cerullo G', 'year': '2020', 'unstructured': 'Cerullo G, Negro M, Parimbelli M, et al.. 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. 10.3389/fimmu.2020.574029', 'journal-title': 'Front Immunol'}, { 'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12879-021-06288-0', 'article-title': 'Effect of vitamin C on mortality of critically ill patients with severe ' 'pneumonia in intensive care unit: a preliminary study', 'volume': '21', 'author': 'Mahmoodpoor A', 'year': '2021', 'unstructured': 'Mahmoodpoor A, Shadvar K, Sanaie S, Hadipoor MR, Pourmoghaddam MA, ' 'Saghaleini SH. Effect of vitamin C on mortality of critically ill ' 'patients with severe pneumonia in intensive care unit: a preliminary ' 'study. BMC Infect Dis. 2021, 21:616. 10.1186/s12879-021-06288-0', 'journal-title': 'BMC Infect Dis'}, { 'key': 'ref16', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/MD.0000000000025876', 'article-title': 'High-dose vitamin C intravenous infusion in the treatment of patients ' 'with COVID-19: a protocol for systematic review and meta-analysis', 'volume': '100', 'author': 'Huang L', 'year': '2021', 'unstructured': 'Huang L, Wang L, Tan J, Liu H, Ni Y. High-dose vitamin C intravenous ' 'infusion in the treatment of patients with COVID-19: a protocol for ' 'systematic review and meta-analysis. Medicine (Baltimore). 2021, ' '100:e25876. 10.1097/MD.0000000000025876', 'journal-title': 'Medicine (Baltimore)'}, { 'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2021.638556', 'article-title': 'High dose intravenous vitamin C for preventing the disease aggravation ' 'of moderate COVID-19 pneumonia. a retrospective propensity matched ' 'before-after study', 'volume': '12', 'author': 'Zhao B', 'year': '2021', 'unstructured': 'Zhao B, Liu M, Liu P, et al.. High dose intravenous vitamin C for ' 'preventing the disease aggravation of moderate COVID-19 pneumonia. a ' 'retrospective propensity matched before-after study. Front Pharmacol. ' '2021, 12:638556. 10.3389/fphar.2021.638556', 'journal-title': 'Front Pharmacol'}, { 'key': 'ref18', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583', 'article-title': 'Vitamin D supplementation to prevent acute respiratory tract ' 'infections: systematic review and meta-analysis of individual ' 'participant data', 'volume': '356', 'author': 'Martineau AR', 'year': '2017', 'unstructured': 'Martineau AR, Jolliffe DA, Hooper RL, et al.. Vitamin D supplementation ' 'to prevent acute respiratory tract infections: systematic review and ' 'meta-analysis of individual participant data. BMJ. 2017, 356:i6583. ' '10.1136/bmj.i6583', 'journal-title': 'BMJ'}, { 'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fpubh.2020.00513', 'article-title': 'A basic review of the preliminary evidence that COVID-19 risk and ' 'severity is increased in vitamin D deficiency', 'volume': '8', 'author': 'Benskin LL', 'year': '2020', 'unstructured': 'Benskin LL. A basic review of the preliminary evidence that COVID-19 ' 'risk and severity is increased in vitamin D deficiency. Front Public ' 'Health. 2020, 8:513. 10.3389/fpubh.2020.00513', 'journal-title': 'Front Public Health'}, { 'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.aimed.2021.01.003', 'article-title': 'Vitamin-D and COVID-19: time for the profession to take a stand', 'volume': '8', 'author': 'Brighthope I', 'year': '2021', 'unstructured': 'Brighthope I, Sali Am A, Ried K. Vitamin-D and COVID-19: time for the ' 'profession to take a stand. Adv Integr Med. 2021, 8:77-8. ' '10.1016/j.aimed.2021.01.003', 'journal-title': 'Adv Integr Med'}, { 'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12967-020-02488-5', 'article-title': 'The importance of vitamin d metabolism as a potential prophylactic, ' 'immunoregulatory and neuroprotective treatment for COVID-19', 'volume': '18', 'author': 'Xu Y', 'year': '2020', 'unstructured': 'Xu Y, Baylink DJ, Chen CS, et al.. The importance of vitamin d ' 'metabolism as a potential prophylactic, immunoregulatory and ' 'neuroprotective treatment for COVID-19. J Transl Med. 2020, 18:322. ' '10.1186/s12967-020-02488-5', 'journal-title': 'J Transl Med'}, { 'key': 'ref22', 'unstructured': 'Meta-analysis of vitamin C Covid-19 treatment studies. (2021). ' 'https.//c19vitaminc.com/.'}, { 'key': 'ref23', 'doi-asserted-by': 'publisher', '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', 'volume': '4', 'author': 'Thomas S', 'year': '2021', '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', 'journal-title': 'JAMA Netw Open'}, { 'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.4149/BLL_2021_119', 'article-title': 'The prognostic significance of vitamin D deficiency in patients with ' 'COVID-19 pneumonia', 'volume': '122', 'author': 'Yildiz M', 'year': '2021', 'unstructured': 'Yildiz M, Senel MU, Kavurgaci S, Ozturk FE, Ozturk A. The prognostic ' 'significance of vitamin D deficiency in patients with COVID-19 ' 'pneumonia. Bratisl Lek Listy. 2021, 122:744-7. 10.4149/BLL_2021_119', 'journal-title': 'Bratisl Lek Listy'}, { 'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00203-021-02482-5', 'article-title': 'The sufficient vitamin D and albumin level have a protective effect on ' 'COVID-19 infection', 'volume': '203', 'author': 'Matin S', 'year': '2021', 'unstructured': 'Matin S, Fouladi N, Pahlevan Y, et al.. The sufficient vitamin D and ' 'albumin level have a protective effect on COVID-19 infection. Arch ' 'Microbiol. 2021, 203:5153-62. 10.1007/s00203-021-02482-5', 'journal-title': 'Arch Microbiol'}, { 'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/febs.15495', 'article-title': 'Low plasma 25(OH) vitamin D level is associated with increased risk of ' 'COVID-19 infection: an Israeli population-based study', 'volume': '287', 'author': 'Merzon E', 'year': '2020', 'unstructured': '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, 287:3693-702. 10.1111/febs.15495', 'journal-title': 'FEBS J'}, { 'key': 'ref27', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/clinem/dgaa733', 'article-title': 'Vitamin D status in hospitalized patients with SARS-CoV-2 infection', 'volume': '106', 'author': 'Hernández JL', 'year': '2021', 'unstructured': 'Hernández JL, Nan D, Fernandez-Ayala M, et al.. Vitamin D status in ' 'hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol ' 'Metab. 2021, 106:e1343-53. 10.1210/clinem/dgaa733', 'journal-title': 'J Clin Endocrinol Metab'}, { 'key': 'ref28', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2021.09.22.21263977', 'article-title': 'COVID-19 mortality risk correlates inversely with vitamin D3 status, ' 'and a mortality rate close to zero could theoretically be achieved at ' '50 ng/ml 25 (OH) D3: results of a systematic review and meta-analysis', 'volume': '13', 'author': 'Borsche L', 'year': '2021', 'unstructured': 'Borsche L, Glauner B, Mendel Jv. COVID-19 mortality risk correlates ' 'inversely with vitamin D3 status, and a mortality rate close to zero ' 'could theoretically be achieved at 50 ng/ml 25 (OH) D3: results of a ' 'systematic review and meta-analysis. Nutrients. 2021, 13:3596. ' '10.1101/2021.09.22.21263977', 'journal-title': 'Nutrients'}, { 'key': 'ref29', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.aimed.2015.11.002', 'article-title': 'Integrative health check reveals suboptimal levels in a number of vital ' 'biomarkers', 'volume': '2', 'author': 'Travica N', 'year': '2015', 'unstructured': 'Travica N, Ried K, Bujnowski R, Sali A. Integrative health check reveals ' 'suboptimal levels in a number of vital biomarkers. Adv Integr Med. 2015, ' '2:135-40. 10.1016/j.aimed.2015.11.002', 'journal-title': 'Adv Integr Med'}, { 'key': 'ref30', 'doi-asserted-by': 'publisher', 'DOI': '10.22038/abjs.2020.47754.2346', 'article-title': 'Prevalence of comorbidities in COVID-19 patients: a systematic review ' 'and meta-analysis', 'volume': '8', 'author': 'Baradaran A', 'year': '2020', 'unstructured': 'Baradaran A, Ebrahimzadeh MH, Baradaran A, Kachooei AR. Prevalence of ' 'comorbidities in COVID-19 patients: a systematic review and ' 'meta-analysis. Arch Bone Jt Surg. 2020, 8:247-55. 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