COVID-19: Poor outcomes in patients with zinc deficiency
Dinesh Jothimani, Ezhilarasan Kailasam, Silas Danielraj, Balaji Nallathambi, Hemalatha Ramachandran, Padmini Sekar, Shruthi Manoharan, Vidyalakshmi Ramani, Gomathy Narasimhan, Ilankumaran Kaliamoorthy, Mohamed Rela
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.09.014
Background: Zinc is a trace element with potent immunoregulatory and antiviral properties, and is utilized in the treatment of coronavirus disease 2019 . However, we do not know the clinical significance of serum Zinc levels in COVID-19 patients. The aim of this study was to determine the clinical significance of serum zinc in COVID-19 patients and to establish a correlation with disease severity. Methods: This was a prospective study of fasting zinc levels in COVID-19 patients at the time of hospitalization. An initial comparative analysis was conducted between COVID-19 patients and healthy controls. COVID-19 patients with zinc deficiency were compared to those with normal zinc levels. Results: COVID-19 patients (n = 47) showed significantly lower zinc levels when compared to healthy controls (n = 45): median 74.5 (interquartile range 53.4-94.6) mg/dl vs 105.8 (interquartile range 95.65-120.90) mg/dl (p < 0.001). Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications (p = 0.009), acute respiratory distress syndrome (18.5% vs 0%, p = 0.06), corticosteroid therapy (p = 0.02), prolonged hospital stay (p = 0.05), and increased mortality (18.5% vs 0%, p = 0.06). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients. Conclusions: The study data clearly show that a significant number of COVID-19 patients were zinc deficient. These zinc deficient patients developed more complications, and the deficiency was associated with a prolonged hospital stay and increased mortality.
Conflict of interest
References
Adhikari, Meng, Wu, Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review, Infect Dis Poverty,
doi:10.1186/s40249-020-00646-xAlexander, Tinkov, Strand, Alehagen, Skalny et al., Early nutritional interventions with zinc, selenium and vitamin D for raising anti-viral resistance against progressive COVID-19, Nutrients,
doi:10.3390/nu12082358Barocas, So-Armah, Cheng, Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia, PLoS One,
doi:10.1371/journal.pone.0218852Devaux, Rolain, Raoult, ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome, J Microbiol Immunol Infect,
doi:10.1016/j.jmii.2020.04.015Ferrari, Wright-Minogue, Fang, Baroudy, Lau et al., Characterization of soluble hepatitis C virus RNA-dependent RNA polymerase expressed in Escherichia coli, J Virol,
doi:10.1128/JVI.73.2.1649-1654.1999Ghaffari, Tavakoli, Moradi, Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine, J Biomed Sci,
doi:10.1186/s12929-019-0563-4Henry, Aggarwal, Wong, Lactate dehydrogenase levels predict coronavirus disease
Iddir, Brito, Dingeo, International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control, Food Nutr Bull,
doi:10.3390/nu12061562Kato, Mcgowan, Machado, Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease, Blood,
doi:10.1182/blood-2005-06-2373Kumar, Kubota, Chernov, Kasuya, Potential role of zinc supplementation in prophylaxis and treatment of COVID-19
Li, Li, Zhang, Wang, Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues, Infect Dis Poverty,
doi:10.1186/s40249-020-00662-xRahman, Idid, Can Zn Be a critical element in COVID-19 treatment?
Read, Obeid, Ahlenstiel, Ahlenstiel, The role of zinc in antiviral immunity, Adv Nutr,
doi:10.1093/advances/Reeves, Dell, An experimental study of the effect of zinc on the activity of angiotensin converting enzyme in serum, Clin Chem,
doi:10.1093/advances/nmz013Shankar, Prasad, Zinc and immune function: the biological basis of altered resistance to infection, Am J Clin Nutr,
doi:10.1093/ajcn/68.2.447SShi, Li, Zhou, Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study, BMC Med,
doi:10.1186/s12916-020-01633-7Skalny, Rink, Ajsuvakova, Zinc and respiratory tract infections: perspectives for COVID-19 (Review), Int J Mol Med,
doi:10.3892/ijmm.2020.4575Towler, Staker, Prasad, ACE2 X-ray structures reveal a large hingebending motion important for inhibitor binding and catalysis, J Biol Chem,
doi:10.1074/jbc.M311191200Velthuis, Van Den Worm, Sims, Baric, Snijder et al., 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,
doi:10.1371/journal.ppat.1001176Pub-lished2010Wintergerst, Maggini, Hornig, Immune-enhancing role of vitamin C and zinc and effect on clinical conditions, Ann Nutr Metab,
doi:10.1159/000090495Yang, Zheng, Gou, Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis, Int J Infect Dis,
doi:10.1016/j.ijid.2020.03.017Yazdanpanah, Hamblin, Rezaei, The immune system and COVID-19: Friend or foe?
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'(COVID-19) severity and mortality: a pooled analysis [published online '
'ahead of print, 2020 May 27]',
'volume': '38',
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'author': 'Ko',
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'author': 'Read',
'year': '2019',
'journal-title': 'Adv Nutr'},
{ 'issue': '4',
'key': '10.1016/j.ijid.2020.09.014_bib0105',
'doi-asserted-by': 'crossref',
'first-page': '581',
'DOI': '10.1093/clinchem/31.4.581',
'article-title': 'An experimental study of the effect of zinc on the activity of '
'angiotensin converting enzyme in serum',
'volume': '31',
'author': 'Reeves',
'year': '1985',
'journal-title': 'Clin Chem'},
{ 'issue': '2 Suppl',
'key': '10.1016/j.ijid.2020.09.014_bib0110',
'doi-asserted-by': 'crossref',
'first-page': '447S',
'DOI': '10.1093/ajcn/68.2.447S',
'article-title': 'Zinc and immune function: the biological basis of altered resistance to '
'infection',
'volume': '68',
'author': 'Shankar',
'year': '1998',
'journal-title': 'Am J Clin Nutr'},
{ 'issue': '1',
'key': '10.1016/j.ijid.2020.09.014_bib0115',
'doi-asserted-by': 'crossref',
'first-page': '168',
'DOI': '10.1186/s12916-020-01633-7',
'article-title': 'Lactate dehydrogenase and susceptibility to deterioration of mild '
'COVID-19 patients: a multicenter nested case-control study',
'volume': '18',
'author': 'Shi',
'year': '2020',
'journal-title': 'BMC Med'},
{ 'issue': '1',
'key': '10.1016/j.ijid.2020.09.014_bib0120',
'first-page': '17',
'article-title': 'Zinc and respiratory tract infections: perspectives for COVID-19 '
'(Review)',
'volume': '46',
'author': 'Skalny',
'year': '2020',
'journal-title': 'Int J Mol Med'},
{ 'issue': '11',
'key': '10.1016/j.ijid.2020.09.014_bib0125',
'doi-asserted-by': 'crossref',
'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',
'year': '2010',
'journal-title': 'PLoS Pathog'},
{ 'issue': '17',
'key': '10.1016/j.ijid.2020.09.014_bib0130',
'doi-asserted-by': 'crossref',
'first-page': '17996',
'DOI': '10.1074/jbc.M311191200',
'article-title': 'ACE2 X-ray structures reveal a large hinge-bending motion important for '
'inhibitor binding and catalysis',
'volume': '279',
'author': 'Towler',
'year': '2004',
'journal-title': 'J Biol Chem'},
{ 'key': '10.1016/j.ijid.2020.09.014_bib0135',
'doi-asserted-by': 'crossref',
'first-page': '1712',
'DOI': '10.3389/fimmu.2020.01712',
'article-title': 'The potential impact of zinc supplementation on COVID-19 pathogenesis',
'volume': '11',
'author': 'Wessels',
'year': '2020',
'journal-title': 'Front Immunol'},
{ 'issue': '2',
'key': '10.1016/j.ijid.2020.09.014_bib0140',
'doi-asserted-by': 'crossref',
'first-page': '85',
'DOI': '10.1159/000090495',
'article-title': 'Immune-enhancing role of vitamin C and zinc and effect on clinical '
'conditions',
'volume': '50',
'author': 'Wintergerst',
'year': '2006',
'journal-title': 'Ann Nutr Metab'},
{ 'issue': '10',
'key': '10.1016/j.ijid.2020.09.014_bib0145',
'doi-asserted-by': 'crossref',
'DOI': '10.1371/journal.pone.0109180',
'article-title': 'Chloroquine is a zinc ionophore',
'volume': '9',
'author': 'Xue',
'year': '2014',
'journal-title': 'PLoS One'},
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'first-page': '91',
'DOI': '10.1016/j.ijid.2020.03.017',
'article-title': 'Prevalence of comorbidities and its effects in patients infected with '
'SARS-CoV-2: a systematic review and meta-analysis',
'volume': '94',
'author': 'Yang',
'year': '2020',
'journal-title': 'Int J Infect Dis'},
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'first-page': '117900',
'DOI': '10.1016/j.lfs.2020.117900',
'article-title': 'The immune system and COVID-19: Friend or foe? [published online ahead '
'of print, 2020 June 2]',
'volume': '256',
'author': 'Yazdanpanah',
'year': '2020',
'journal-title': 'Life Sci'}],
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