Horm Metab Res 2020; 52(07): 540-546
DOI: 10.1055/a-1182-2016
Hypothesis

Is There a Role for Environmental and Metabolic Factors Predisposing to Severe COVID-19?

Stefan R. Bornstein
1   Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
3   Department of Diabetes, School of Life Course Science and Medicine, Kingʼs College London, London, UK
4   Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, University Hospital, Zürich, Switzerland
,
Karin Voit-Bak
5   Zentrum für Apherese- und Hämofiltration am INUS Tagesklinikum-Cham, Cham, Germany
,
Dieter Schmidt
5   Zentrum für Apherese- und Hämofiltration am INUS Tagesklinikum-Cham, Cham, Germany
,
Henning Morawietz
6   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Alexander Benjamin Bornstein
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Waldimir Balanzew
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Ulrich Julius
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Roman N. Rodionov
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Anne Maria Biener
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Jun Wang
2   Department of Medicine III, University Hospital Carl Gustav Carus at the Technische Universität, Dresden, Germany
,
Klaus-Martin Schulte
7   Department of Endocrine Surgery, King's College Hospital NHS Foundation Trust, London, UK
8   ACRF Department of Cancer, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
,
Peter Krebs
9   Institute of Urban and Industrial Water Management, Technische Universität Dresden, Dresden, Germany
,
Günter Vollmer
10   Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany
,
R. Straube
5   Zentrum für Apherese- und Hämofiltration am INUS Tagesklinikum-Cham, Cham, Germany
› Author Affiliations
Funding Information This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (grant numbers MO 1695/5-1 and -2) and the Excellence Initiative by the German Federal State Governments (Institutional Strategy, measure “support the best”, grant number 3-2, F03661- 553-41B-1250000). Klaus-Martin Schulte is supported by the Max Lindemann Memorial Fund.

Abstract

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic affects people around the world. However, there have been striking differences in the number of infected individuals and deaths in different countries. Particularly, within Central Europe in countries that are similar in ethnicity, age, and medical standards and have performed similar steps of containment, such differences in mortality rates remain inexplicable. We suggest to consider and explore environmental factors to explain these intriguing variations. Countries like Northern Italy, France, Spain, and UK have suffered from 5 times more deaths from the corona virus infection than neighboring countries like Germany, Switzerland, Austria, and Denmark related to the size of their respective populations. There is a striking correlation between the level of environmental pollutants including pesticides, dioxins, and air pollution such as NO2 known to affect immune function and healthy metabolism with the rate of mortality in COVID-19 pandemic in these European countries. There is also a correlation with the use of chlorination of drinking water in these regions. In addition to the improvement of environmental protective programs, there are possibilities to lower the blood levels of these pollutants by therapeutic apheresis. Furthermore, therapeutic apheresis might be an effective method to improve metabolic inflammation, altered vascular perfusion, and neurodegeneration observed as long-term complications of COVID-19 disease.



Publication History

Received: 08 May 2020

Accepted: 15 May 2020

Article published online:
29 June 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Ioannidis JPA. Coronavirus disease 2019: the harms of exaggerated information and non-evidence-based measures. Eur J Clin Invest 2020; DOI: 10.1111/eci.13223. : e13223
  • 2 Boccia S, Ricciardi W, Ioannidis JPA. What other countries can learn from italy during the COVID-19 pandemic. JAMA Intern Med 2020; DOI: 10.1001/jamainternmed.2020.1447.
  • 3 Bedford J, Enria D, Giesecke J. et al. COVID-19: towards controlling of a pandemic. Lancet 2020; 395: 1015-1018
  • 4 Koo JR, Cook AR, Park M. et al. Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study. Lancet Infect Dis 2020; DOI: 10.1016/S1473-3099(20)30162-6.
  • 5 Prem K, Liu Y, Russell TW. et al. The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study. Lancet Public Health 2020; 5: e261-e270
  • 6 Sorbello M, El-Boghdadly K, Di Giacinto I. et al. The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice. Anaesthesia 2020; 75: 724-732
  • 7 Kinross P, Suetens C, Gomes Dias J. et al. Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020. Euro Surveill 2020; 25 DOI: 10.2807/1560-7917.ES.2020.25.11.2000285.
  • 8 Bornstein SR, Dalan R, Hopkins D. et al. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol 2020; 16: 297-298
  • 9 Bornstein SR, Rubino F, Khunti K. et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol 2020; DOI: 10.1016/S2213-8587(20)30152-2.
  • 10 Dalan R, Bornstein SR, El-Armouche A. et al. The ACE-2 in COVID-19: Foe or Friend?. Horm Metab Res 2020; 52: 257-263
  • 11 Steenblock C, Todorov V, Kanczkowski W. et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the neuroendocrine stress axis. Mol Psychiatry 2020; DOI: 10.1038/s41380-020-0758-9.
  • 12 Russell D, Blain PG, Rice P. Clinical management of casualties exposed to lung damaging agents: a critical review. Emerg Med J 2006; 23: 421-424
  • 13 McGovern TK, Powell WS, Day BJ. et al. Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma. Respir Res 2010; 11: 138
  • 14 Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992; 262: L367-L385
  • 15 Zarogiannis SG, Jurkuvenaite A, Fernandez S. et al. Ascorbate and deferoxamine administration after chlorine exposure decrease mortality and lung injury in mice. Am J Respir Cell Mol Biol 2011; 45: 386-392
  • 16 Austin EW, Parrish JM, Kinder DH. et al. Lipid peroxidation and formation of 8-hydroxydeoxyguanosine from acute doses of halogenated acetic acids. Fundam Appl Toxicol 1996; 31: 77-82
  • 17 French AS, Copeland CB, Andrews D. et al. Evaluation of the potential immunotoxicity of bromodichloromethane in rats and mice. J Toxicol Environ Health A 1999; 56: 297-310
  • 18 French AS, Copeland CB, Andrews DL. et al. Evaluation of the potential immunotoxicity of chlorinated drinking water in mice. Toxicology 1998; 125: 53-58
  • 19 Exon JH, Koller LD, O’Reilly CA. et al. Immunotoxicologic evaluation of chlorine-based drinking water disinfectants, sodium hypochlorite and monochloramine. Toxicology 1987; 44: 257-269
  • 20 Shopp GM, Sanders VM, White KL. et al. Humoral and cell-mediated immune status of mice exposed to trans-1,2-dichloroethylene. Drug Chem Toxicol 1985; 8: 393-407
  • 21 Lu WQ, Chen XN, Yue F. et al. Studies on the in vivo and in vitro mutagenicity and the lipid peroxidation of chlorinated surface (drinking) water in rats and metabolically competent human cells. Mutat Res 2002; 513: 151-157
  • 22 Xu L, Liu J, Lu M. et al. Liver injury during highly pathogenic human coronavirus infections. Liver Int 2020; 40: 998-1004
  • 23 Parohan M, Yaghoubi S, Seraj A. Liver injury is associated with severe Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of retrospective studies. Hepatol Res 2020; DOI: 10.1111/hepr.13510.
  • 24 Reis A, Spickett CM. Chemistry of phospholipid oxidation. Biochim Biophys Acta 2012; 1818: 2374-2387
  • 25 Ali SN, Ahmad MK, Mahmood R. Sodium chlorate, a herbicide and major water disinfectant byproduct, generates reactive oxygen species and induces oxidative damage in human erythrocytes. Environ Sci Pollut Res Int 2017; 24: 1898-1909
  • 26 Ali SN, Mahmood R. Sodium chlorite increases production of reactive oxygen species that impair the antioxidant system and cause morphological changes in human erythrocytes. Environ Toxicol 2017; 32: 1343-1353
  • 27 Ebenezer DL, Fu P, Ramchandran R. et al. S1P and plasmalogen derived fatty aldehydes in cellular signaling and functions. Biochim Biophys Acta Mol Cell Biol Lipids 2020; 1865: 158681
  • 28 Sun X, Wang T, Cai D. et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020; DOI: 10.1016/j.cytogfr.2020.04.002.
  • 29 Geng YJ, Wei ZY, Qian HY. et al. Pathophysiological characteristics and therapeutic approaches for pulmonary injury and cardiovascular complications of coronavirus disease 2019. Cardiovasc Pathol 2020; 47: 107228
  • 30 Salome B, Magen A. Dysregulation of lung myeloid cells in COVID-19. Nat Rev Immunol 2020; 20: 277
  • 31 Desforges JP, Sonne C, Levin M. et al. Immunotoxic effects of environmental pollutants in marine mammals. Environ Int 2016; 86: 126-139
  • 32 Vlaanderen J, van Veldhoven K, Font-Ribera L. et al. Acute changes in serum immune markers due to swimming in a chlorinated pool. Environ Int 2017; 105: 1-11
  • 33 Lanin DV, Zaytseva NV, Zamlyanova MA. et al. Characteristics of regulatory system in children exposed to the environmental chemical factors. Gig Sanit 2014; 23-26
  • 34 Trikha P, Lee DA. The role of AhR in transcriptional regulation of immune cell development and function. Biochim Biophys Acta Rev Cancer 2020; 1873: 188335
  • 35 Rothhammer V, Quintana FJ. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol 2019; 19: 184-197
  • 36 Koch CA. How Can Environmental Factors Contribute to the Incidence of Thyroid Cancer?. Horm Metab Res 2017; 49: 229-231
  • 37 Pang C, Zhu C, Zhang Y. et al. 2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell. Toxicol Lett 2019; 311: 49-57
  • 38 Feng Y, Tian J, Krylova I. et al. Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model. J Environ Sci (China) 2016; 39: 218-227
  • 39 North CM, Crawford RB, Lu H. et al. 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated suppression of toll-like receptor stimulated B-lymphocyte activation and initiation of plasmacytic differentiation. Toxicol Sci 2010; 116: 99-112
  • 40 Li Y, Xie HQ, Zhang W. et al. Type 3 innate lymphoid cells are altered in colons of C57BL/6 mice with dioxin exposure. Sci Total Environ 2019; 662: 639-645
  • 41 Cervantes-Barragan L, Colonna M. Chemical sensing in development and function of intestinal lymphocytes. Curr Opin Immunol 2018; 50: 112-116
  • 42 Ross PS, de Swart RL, van der Vliet H. et al. Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD. Arch Toxicol 1997; 71: 563-574
  • 43 Holsapple MP, Snyder NK, Wood SC. et al. A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update. Toxicology 1991; 69: 219-255
  • 44 Yang YG, Lebrec H, Burleson GR. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pulmonary influenza virus titer and natural killer (NK) activity in rats. Fundam Appl Toxicol 1994; 23: 125-131
  • 45 Burleson GR, Lebrec H, Yang YG. et al. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on influenza virus host resistance in mice. Fundam Appl Toxicol 1996; 29: 40-47
  • 46 Kumar J, Lind PM, Salihovic S. et al. Influence of persistent organic pollutants on the complement system in a population-based human sample. Environ Int 2014; 71: 94-100
  • 47 Weis GCC, Assmann CE, Cadona FC. et al. Immunomodulatory effect of mancozeb, chlorothalonil, and thiophanate methyl pesticides on macrophage cells. Ecotoxicol Environ Saf 2019; 182: 109420
  • 48 Ryu DH, Yu HT, Kim SA. et al. Is chronic exposure to low-dose organochlorine pesticides a new risk factor of T-cell immunosenescence?. Cancer Epidemiol Biomarkers Prev 2018; 27: 1159-1167
  • 49 Qiu S, Fu H, Zhou R. et al. Toxic effects of glyphosate on intestinal morphology, antioxidant capacity and barrier function in weaned piglets. Ecotoxicol Environ Saf 2020; 187: 109846
  • 50 Knutsen HK, Alexander J, Barregård L. et al. Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food. EFSA Journal 2018; 16: 5333
  • 51 Grandjean P, Andersen EW, Budtz-Jorgensen E. et al. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA 2012; 307: 391-397
  • 52 Abraham K, Mielke H, Fromme H. et al. Internal exposure to perfluoroalkyl substances (PFASs) and biological markers in 101 healthy 1-year-old children: associations between levels of perfluorooctanoic acid (PFOA) and vaccine response. Arch Toxicol 2020; DOI: 10.1007/s00204-020-02715-4.
  • 53 Looker C, Luster MI, Calafat AM. et al. Influenza vaccine response in adults exposed to perfluorooctanoate and perfluorooctanesulfonate. Toxicol Sci 2014; 138: 76-88
  • 54 Peden-Adams MM, Keller JM, Eudaly JG, Berger J. et al. Suppression of humoral immunity in mice following exposure to perfluorooctane sulfonate. Toxicol Sci 2008; 104: 144-154
  • 55 Ogen Y. Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality. Sci Total Environ 2020; 726: 138605
  • 56 Estrella B, Naumova EN, Cepeda M. et al. Effects of air pollution on lung innate lymphoid cells: Review of in vitro and in vivo experimental studies. Int J Environ Res Public Health 2019; 16 pii: E2347. DOI: 10.3390/ijerph16132347.
  • 57 Ji X, Han M, Yun Y. et al. Acute nitrogen dioxide (NO2) exposure enhances airway inflammation via modulating Th1/Th2 differentiation and activating JAK-STAT pathway. Chemosphere 2015; 120: 722-728
  • 58 Cetkovic-Cvrlje M, Olson M, Schindler B. et al. Exposure to DDT metabolite p,p'-DDE increases autoimmune type 1 diabetes incidence in NOD mouse model. J Immunotoxicol 2016; 13: 108-118
  • 59 Hoyeck MP, Blair H, Ibrahim M. et al. Long-term metabolic consequences of acute dioxin exposure differ between male and female mice. Sci Rep 2020; 10: 1448
  • 60 Kim YA, Park JB, Woo MS. et al. Persistent organic pollutant-mediated insulin resistance. Int J Environ Res Public Health 2019; 16 pii: E448. DOI: 10.3390/ijerph16030448.
  • 61 Huang CY, Wu CL, Yang YC. et al. Association between dioxin and diabetes mellitus in an endemic area of exposure in Taiwan: A population-based study. Medicine (Baltimore) 2015; 94: e1730
  • 62 Arisawa K. Recent decreasing trends of exposure to PCDDs/PCDFs/dioxin-like PCBs in general populations, and associations with diabetes, metabolic syndrome, and gout/hyperuricemia. J Med Invest 2018; 65: 151-161
  • 63 Koch CA, Diamanti-Kandarakis E. Introduction to endocrine disrupting chemicals–is it time to act?. Rev Endocr Metab Disord 2015; 16: 269-270
  • 64 Mao S, Chen G, Liu F. et al. Long-term effects of ambient air pollutants to blood lipids and dyslipidemias in a Chinese rural population. Environ Pollut 2020; 256: 113403
  • 65 Jin C, Zeng Z, Wang C. et al. Insights into a possible mechanism underlying the connection of carbendazim-induced lipid metabolism disorder and gut microbiota dysbiosis in mice. Toxicol Sci 2018; 166: 382-393
  • 66 Liu Q, Wang Q, Xu C. et al. Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism. Sci Rep 2017; 7: 46339
  • 67 Crow KD. Lipid profiles in dioxin-exposed workers. Lancet 1979; 1: 982
  • 68 Pelclova D, Fenclova Z, Preiss J. et al. Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8- tetrachlordibenzo- p-dioxin. Int Arch Occup Environ Health 2002; 75 (Suppl. 01) S60-S66
  • 69 Wu Q, Zhou L, Sun X. et al. Altered lipid metabolism in recovered sars patients twelve years after infection. Sci Rep 2017; 7: 9110
  • 70 Guo T, Fan Y, Chen M. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.1017.
  • 71 Kaur N, Starling AP, Calafat AM. et al. Longitudinal association of biomarkers of pesticide exposure with cardiovascular disease risk factors in youth with diabetes. Environ Res 2020; 181: 108916
  • 72 Ashbolt NJ. Risk analysis of drinking water microbial contamination versus disinfection by-products (DBPs). Toxicology 2004; 198: 255-262
  • 73 Bornstein SR, Voit-Bak K, Rosenthal P. et al. Extracorporeal apheresis therapy for Alzheimer disease-targeting lipids, stress, and inflammation. Mol Psychiatry 2020; 25: 275-282
  • 74 Palm NW, Medzhitov R. Not so fast: adaptive suppression of innate immunity. Nat Med 2007; 13: 1142-1144
  • 75 Liu J, Li S, Liu J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763
  • 76 Lin JH, Chen YC, Lu CL. et al. Application of plasma exchange in association with higher dose CVVH in cytokine storm complicating COVID-19. J Formos Med Assoc 2020; DOI: 10.1016/j.jfma.2020.04.023.
  • 77 Straube R, Muller G, Voit-Bak K. et al. Metabolic and non-metabolic peripheral neuropathy: Is there a place for therapeutic apheresis?. Horm Metab Res 2019; 51: 779-784