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Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction

Sethuram et al., Reproductive Sciences, doi:10.1007/s43032-020-00400-6
Jan 2021  
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Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020
 
*, now with p = 0.00000064 from 45 studies, recognized in 17 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,500+ studies for 81 treatments. c19early.org
Review of zinc deficiency and supplementation for COVID-19, including potential impacts on reproductive health.
Reviews covering zinc for COVID-19 include1-13.
Sethuram et al., 7 Jan 2021, peer-reviewed, 3 authors.
This PaperZincAll
Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction
Ramya Sethuram, David Bai, Husam M Abu-Soud
Reproductive Sciences, doi:10.1007/s43032-020-00400-6
COVID-19 (coronavirus disease 2019) is the current world health crisis, producing extensive morbidity and mortality across all age groups. Given the established roles of zinc in combating oxidative damage and viral infections, zinc is being trialed as a treatment modality against COVID-19. Zinc also has confirmed roles in both male and female reproduction. The possible depletion of zinc with the oxidative events of COVID-19 is especially relevant to the fertility of affected couples. This review aims to present the pathophysiology of COVID-19, especially in relation to reproductive function; the role of zinc in the COVID-19 disease process; and how zinc depletion in concert with cytokine storm and reactive oxygen species production could affect reproduction. It also highlights research areas to better the understanding of COVID-19 and its impact on fertility and potential ways to mitigate the impact.
Compliance with Ethical Standards Research Involving Human Participants/Animals This manuscript did not make use of human or animal participants or samples. Conflict of Interest The authors declare that they have no conflict of interest. Informed Consent N/A
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Sci.'}, { 'issue': '6', 'key': '400_CR31', 'first-page': 'e01337', 'volume': '94', 'author': 'M Ficarelli', 'year': '2020', 'unstructured': 'Ficarelli M, Antzin-Anduetza I, Hugh-White R, Firth AE, Sertkaya H, ' 'Wilson H, et al. CpG dinucleotides inhibit HIV-1 replication through ' 'zinc finger antiviral protein (ZAP)-dependent and -independent ' 'mechanisms. J Virol 2020. 2020;94(6):e01337–19.', 'journal-title': 'J Virol 2020'}, { 'key': '400_CR32', 'doi-asserted-by': 'publisher', 'first-page': '1286', 'DOI': '10.3390/nu9121286', 'volume': '9', 'author': 'I Wessels', 'year': '2017', 'unstructured': 'Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. ' 'Nutrients. 2017;9:1286.', 'journal-title': 'Nutrients'}, { 'issue': '4', 'key': '400_CR33', 'first-page': '696', 'volume': '10', 'author': 'SA Read', 'year': '2019', 'unstructured': 'Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The Role of Zinc in ' 'Antiviral. Immunity. 2019 Jul 1;10(4):696–710.', 'journal-title': 'Immunity.'}, { 'issue': '20', 'key': '400_CR34', 'first-page': '31961', 'volume': 'S0012–3692', 'author': 'JS Yao', 'year': '2020', 'unstructured': 'Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, et al. The ' 'minimal effect of zinc on the survival of hospitalized patients with ' 'Covid-19: an observational study. Chest. 2020 Jul ' '22;S0012–3692(20):31961–9.', 'journal-title': 'Chest.'}, { 'issue': '2', 'key': '400_CR35', 'first-page': '69', 'volume': '19', 'author': 'A Fallah', 'year': '2018', 'unstructured': 'Fallah A, Mohammad-Hasani A, Colagar AH. Zinc is an essential element ' 'for male fertility: a review of Zn roles in men’s health, germination, ' 'sperm quality, and fertilization. J Reprod Infertil. Apr-Jun ' '2018;19(2):69–81.', 'journal-title': 'J Reprod Infertil.'}, { 'issue': '7', 'key': '400_CR36', 'doi-asserted-by': 'publisher', 'first-page': '679', 'DOI': '10.1177/0960327114559611', 'volume': '34', 'author': 'P Sengupta', 'year': '2015', 'unstructured': 'Sengupta P, Banerjee R, Nath S, Das S. Banerjee S Metals and female ' 'reproductive toxicity. Hum Exp Toxicol. 2015 Jul;34(7):679–97.', 'journal-title': 'Hum Exp Toxicol.'}, { 'key': '400_CR37', 'doi-asserted-by': 'publisher', 'first-page': '152466', 'DOI': '10.1016/j.tox.2020.152466', 'volume': '439', 'author': 'ZA Yahfoufi', 'year': '2020', 'unstructured': 'Yahfoufi ZA, Bai D, Khan SN, Chatzicharalampous C, Kohan-Ghadr H, Morris ' 'RT, et al. Glyphosate induces metaphase II oocyte deterioration and ' 'embryo damage by zinc depletion and overproduction of reactive oxygen ' 'species. Toxicology. 2020 Jun;439:152466.', 'journal-title': 'Toxicology.'}, { 'issue': '2', 'key': '400_CR38', 'doi-asserted-by': 'publisher', 'first-page': '135', 'DOI': '10.1039/C6IB00212A', 'volume': '9', 'author': 'EL Que', 'year': '2017', 'unstructured': 'Que EL, Duncan FE, Bayer AR, Philips SJ, Roth EW, Bleher R, et al. Zinc ' 'sparks induce physiochemical changes in the egg zona pellucida that ' 'prevent polyspermy. Integr Biol (Camb). 2017 Feb 20;9(2):135–44.', 'journal-title': 'Integr Biol (Camb).'}, { 'key': '400_CR39', 'doi-asserted-by': 'publisher', 'first-page': '22772', 'DOI': '10.1038/srep22772', 'volume': '6', 'author': 'N Zhang', 'year': '2016', 'unstructured': 'Zhang N, Duncan FE, Que EL, O’Halloran TV, Woodruff TK. The ' 'fertilization-induced zinc spark is a novel biomarker of mouse embryo ' 'quality and early development. Sci Rep. 2016 Mar 18;6:22772.', 'journal-title': 'Sci Rep.'}, { 'issue': '6', 'key': '400_CR40', 'doi-asserted-by': 'publisher', 'first-page': '414', 'DOI': '10.1002/bdra.10046', 'volume': '67', 'author': 'LA Hanna', 'year': '2003', 'unstructured': 'Hanna LA, Clegg MS, Momma TY, Daston GP, Rogers JM, Keen CL. Zinc ' 'influences the in vitro development of peri-implantation mouse embryos. ' 'Birth Defects Res A Clin Mol Teratol. 2003 Jun;67(6):414–20.', 'journal-title': 'Birth Defects Res A Clin Mol Teratol'}, { 'key': '400_CR41', 'doi-asserted-by': 'publisher', 'first-page': '427', 'DOI': '10.1038/254427a0', 'volume': '25', 'author': 'L Hurley', 'year': '1975', 'unstructured': 'Hurley L, Shrader R. Abnormal development of preimplantation rat eggs ' 'after three days of maternal zinc deficiency. Nature. 1975;25:427–9.', 'journal-title': 'Nature'}, { 'key': '400_CR42', 'doi-asserted-by': 'publisher', 'first-page': '133', 'DOI': '10.1146/annurev-nutr-080508-141119', 'volume': '29', 'author': 'H Haase', 'year': '2009', 'unstructured': 'Haase H, Rink L. Functional significance of zinc-related signaling ' 'pathways in immune cells. Annu Rev Nutr. 2009;29:133–52.', 'journal-title': 'Annu Rev Nutr'}, { 'key': '400_CR43', 'doi-asserted-by': 'publisher', 'first-page': '2263S', 'DOI': '10.1093/jn/125.suppl_8.2263S', 'volume': '125', 'author': 'MS Golub', 'year': '1995', 'unstructured': 'Golub MS, Keen CL, Gershwin ME, Hendrickx AG. Developmental zinc ' 'deficiency and behavior. J Nutr. 1995;125:2263S–71S.', 'journal-title': 'J Nutr'}, { 'key': '400_CR44', 'doi-asserted-by': 'publisher', 'first-page': '692', 'DOI': '10.3181/00379727-123-31578', 'volume': '123', 'author': 'LS Hurley', 'year': '1966', 'unstructured': 'Hurley LS, Swenerton H. Congenital malformations resulting from zinc ' 'deficiency in rats. Proc Soc Exp Biol Med. 1966;123:692–6.', 'journal-title': 'Proc Soc Exp Biol Med'}, { 'key': '400_CR45', 'first-page': '99', 'volume': '129', 'author': 'AO Cavdar', 'year': '1983', 'unstructured': 'Cavdar AO, Babacan E, Asik S, Arcasoy A, Ertem U, Himmetoglu O, et al. ' 'Zinc levels of serum, plasma, erythrocytes and hair in Turkish women ' 'with anencephalic babies. Prog Clin Biol Res. 1983;129:99–106.', 'journal-title': 'Prog Clin Biol Res'}, { 'key': '400_CR46', 'doi-asserted-by': 'publisher', 'first-page': '421', 'DOI': '10.1006/dbio.2001.0346', 'volume': '236', 'author': 'C Chiang', 'year': '2001', 'unstructured': 'Chiang C, Litingtung Y, Harris MP, Simandl BK, Li Y, Beachy PA, et al. ' 'Manifestation of the limb prepattern: limb development in the absence of ' 'sonic hedgehog function. 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J Androl. 2000;21(1):53–7.', 'journal-title': 'J Androl.'}, { 'issue': '2', 'key': '400_CR49', 'doi-asserted-by': 'publisher', 'first-page': '260', 'DOI': '10.1016/S0015-0282(01)02974-0', 'volume': '77', 'author': 'W Eggert-Kruse', 'year': '2002', 'unstructured': 'Eggert-Kruse W, Zwick EM, Batschulat K, Rohr G, Armbruster FP, Petzoldt ' 'D, et al. Are zinc levels in seminal plasma associated with seminal ' 'leukocytes and other determinants of semen quality? Fertil Steril. ' '2002;77(2):260–9.', 'journal-title': 'Fertil Steril.'}, { 'issue': '4', 'key': '400_CR50', 'first-page': '339', 'volume': '30', 'author': 'B Roy', 'year': '2013', 'unstructured': 'Roy B, Baghel RPS, Mohanty TK, Mondal G. Zinc and male reproduction in ' 'domestic animals: a review. Indian J Anim Nutr. 2013;30(4):339–50.', 'journal-title': 'Indian J Anim Nutr.'}, { 'issue': '1', 'key': '400_CR51', 'doi-asserted-by': 'publisher', 'first-page': '148', 'DOI': '10.1093/ajcn/56.1.148', 'volume': '56', 'author': 'CD Hunt', 'year': '1992', 'unstructured': 'Hunt CD, Johnson PE, Herbel J, Mullen LK. Effects of dietary zinc ' 'depletion on seminal volume and zinc loss, serum testosterone ' 'concentrations, and sperm morphology in young men. Am J Clin Nutr. ' '1992;56(1):148–57.', 'journal-title': 'Am J Clin Nutr.'}, { 'issue': '3', 'key': '400_CR52', 'doi-asserted-by': 'publisher', 'first-page': '359', 'DOI': '10.3945/jn.110.131318', 'volume': '141', 'author': 'TP Croxford', 'year': '2011', 'unstructured': 'Croxford TP, McCormick NH, Kelleher SL. Moderate zinc deficiency reduces ' 'testicular Zip6 and Zip10 abundance and impairs spermatogenesis in mice. 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Free Radic Biol Med. 2017 Nov;112:445–51.', 'journal-title': 'Free Radic Biol Med.'}, { 'issue': '2', 'key': '400_CR57', 'doi-asserted-by': 'crossref', 'first-page': '138', 'DOI': '10.25122/jml-2019-0107', 'volume': '13', 'author': 'T Hajjar', 'year': '2020', 'unstructured': 'Hajjar T, Soleymani F, Vatanchian M. Protective effect of vitamin C and ' 'zinc as an antioxidant against chemotherapy-induced male reproductive ' 'toxicity. J Med Life. 2020 Apr-Jun;13(2):138–43.', 'journal-title': 'J Med Life.'}, { 'issue': '4', 'key': '400_CR58', 'doi-asserted-by': 'publisher', 'first-page': '593', 'DOI': '10.1007/s10815-013-9961-9', 'volume': '30', 'author': 'G Azizollahi', 'year': '2013', 'unstructured': 'Azizollahi G, Azizollahi S, Babaei H, Kianinejad M, Baneshi MR, ' 'Nematollahi-mahani SN. Effects of supplement therapy on sperm ' 'parameters, protamine content and acrosomal integrity of ' 'varicocelectomized subjects. 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