Horm Metab Res 2020; 52(07): 471-484
DOI: 10.1055/a-1172-1352
Review

Endocrine Conditions and COVID-19

1   Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA
2   Clinical Research Branch, National Institute of Environmental Health Sciences, NIH, North Carolina, USA
,
1   Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA
,
Crystal D. C. Kamilaris
1   Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA
,
Graeme Eisenhofer
3   Institute of Clinical Chemistry and Laboratory Medicine, and Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
4   Endocrinology Division, Internal Medicine Department, University Hospital “Dr. Jose E. Gonzalez”, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
5   Plataforma INVEST-KER Unit Mayo Clinic, School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
,
Michelle Hajdenberg
6   College of Arts and Sciences at Washington University in St. Louis, Saint Louis, Missouri, USA
,
Joselyne Tonleu
2   Clinical Research Branch, National Institute of Environmental Health Sciences, NIH, North Carolina, USA
,
Janet E. Hall
2   Clinical Research Branch, National Institute of Environmental Health Sciences, NIH, North Carolina, USA
,
7   Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada
,
Forbes Porter
8   Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA
,
Constantine A. Stratakis
1   Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA
,
1   Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA
› Author Affiliations
Funding Information This work was funded by the intramural research program of the National Institutes of Health.

Abstract

COVID-19 was declared a global pandemic by the WHO and has affected millions of patients around the world. COVID-19 disproportionately affects persons with endocrine conditions, thus putting them at an increased risk for severe disease. We discuss the mechanisms that place persons with endocrine conditions at an additional risk for severe COVID-19 and review the evidence. We also suggest precautions and management of endocrine conditions in the setting of global curfews being imposed and offer practical tips for uninterrupted endocrine care.



Publication History

Received: 22 April 2020

Accepted: 30 April 2020

Article published online:
08 June 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 WHO Director-General’s opening remarks at the media briefing on COVID-19; 11 March 2020 (press release); 2020
  • 2 Coronavirus disease (COVID-2019) situation reports (press release). Online, March 16, 2020
  • 3 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020; 395: 1054-1062
  • 4 Health LDo. Louisiana Department of Health Updates for 3/27/2020 Online: ldh.la.gov; 2020 cited Louisiana Department of Health. Available from http://ldh.la.gov/index.cfm/newsroom/detail/5517
  • 5 Center ICNAaR. Report on 775 patients critically ill with COVID-19 2020; updated March 27, 2020. Available from https://www.icnarc.org/About/Latest-News/2020/03/27/Report-On-775-Patients-Critically-Ill-With-Covid-19
  • 6 Garg S, Kim L, Whitaker M. et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 – COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 458-464
  • 7 WHO. Q & A on coronaviruses (COVID-19) (Guidance). 2020; updated March 9, 2020. Available from https://www.who.int/news-room/q-a-detail/q-a-coronaviruses
  • 8 Prevention CfDCa. People who are at higher risk for severe illness. Online; 2020 March 26, 2020
  • 9 Wan Y, Shang J, Graham R. et al. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020; 94: e00127-20 DOI: 10.1128/JVI.00127-20.
  • 10 Hoffmann M, Kleine-Weber H, Schroeder S. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: e8
  • 11 Muniyappa R, Gubbi S. COVID-19 pandemic, corona viruses, and diabetes mellitus. Am J Physiol Endocrinol Metab 2020; 318: E736-E741
  • 12 Roca-Ho H, Riera M, Palau V. et al. Characterization of ACE and ACE2 expression within different organs of the NOD mouse. Int J Mol Sci 2017; 18: 563
  • 13 Salem ESB, Grobe N, Elased KM. Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice. Am J Physiol Renal Physiol 2014; 306: F629-F639
  • 14 Yang JK, Lin SS, Ji XJ. et al. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol 2010; 47: 193-199
  • 15 Zhang W, Xu Y-Z, Liu B. et al. Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis. Sci World J. 2014: 603409
  • 16 Calvet HM, Yoshikawa TT. Infections in Diabetes. Infect Dis Clin North Am 2001; 15: 407-421
  • 17 Geerlings SE, Hoepelman AIM. Immune dysfunction in patients with diabetes mellitus [DM]. FEMS Immunol Med Microbiol 1999; 26: 259-265
  • 18 Daryabor G, Kabelitz D, Kalantar K. An update on immune dysregulation in obesity-related insulin resistance. Scand J Immunol 2019; 89: e12747
  • 19 Varin EM, Mulvihill EE, Beaudry JL. et al. Circulating levels of soluble dipeptidyl peptidase-4 are dissociated from inflammation and induced by enzymatic DPP4 inhibition. Cell Metab. 2019; 29: e5
  • 20 Anoop S, Misra A, Bhatt SP. et al. High circulating plasma dipeptidyl peptidase- 4 levels in non-obese Asian Indians with type 2 diabetes correlate with fasting insulin and LDL-C levels, triceps skinfolds, total intra-abdominal adipose tissue volume and presence of diabetes: A case–control study. BMJ Open Diabetes Res Care 2017; 5: e000393 DOI: 10.1136/ bmjdrc-2017-000393.
  • 21 Stengel A, Goebel-Stengel M, Teuffel P. et al. Obese patients have higher circulating protein levels of dipeptidyl peptidase IV. Peptides 2014; 61: 75-82
  • 22 Ryskjaer J, Deacon CF, Carr RD. et al. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake. Eur J Endocrinol 2006; 155: 485-493
  • 23 Kleine-Weber H, Schroeder S, Krüger N. et al. Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus. Emerg Microbes Infect 2020; 9: 155-168
  • 24 Raj VS, Mou H, Smits SL. et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013; 495: 251-254
  • 25 Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role?. Diabetes Res Clin Pract 2020; 162: 108125
  • 26 Makdissi A, Ghanim H, Vora M. et al. Sitagliptin exerts an antinflammatory action. J Clin Endocrinol Metab 2012; 97: 3333-3341
  • 27 Zhuge F, Ni Y, Nagashimada M. et al. DPP-4 inhibition by linagliptin attenuates obesity-related inflammation and insulin resistance by regulating M1/M2 macrophage polarization. Diabetes 2016; 65: 2966-2979
  • 28 Mehta P, McAuley DF, Brown M. et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033-1034
  • 29 Yang X, Yu Y, Xu J. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet. Respir Med 2020; DOI: 10.1016/ S2213-600(20)30079-5.
  • 30 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506
  • 31 Zhang JJ, Dong X, Cao YY. et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China Allergy. 2020 DOI: 10.1111/all.14238
  • 32 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323: 1061-1069
  • 33 Xu XW, Wu XX, Jiang XG. et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus [SARS-Cov-2] outside of Wuhan, China: Retrospective case series. BMJ 2020; 368: m606
  • 34 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395: 507-513
  • 35 Lu R, Zhao X, Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020; 395: 565-574
  • 36 Cao B, Wang Y, Wen D. et al. A Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; DOI: 10.1056/NEJMoa2001282.
  • 37 Chen C, Chen C, Yan JT. et al. Analysis of myocardial injury and cardiovascular disease in critically ill patients with new type of coronavirus pneumonia (J/OL). Chin J Cardiovasc Dis 2020; 48 DOI: 10.3760/cma.j.cn112148-20200225-00123.
  • 38 Arentz M, Yim E, Klaff L. et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020; 323: 1612-1614
  • 39 Shi Y, Yu X, Zhao H. et al. Host susceptibility to severe COVID-19 and establishment of a host risk score: Findings of 487 cases outside Wuhan. Critical Care 2020; 24: 108
  • 40 Qian GQ, Yang NB, Ding F et al. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. QJM 2020; pii: heaqa089, doi: 10.1093/qjmed/hcaa089
  • 41 Chan JF-W, Yuan S, Kok K-H. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395: 514-523
  • 42 Goyal P, Choi JJ, Pinheiro LC. et al. Clinical characteristics of Covid-19 in New York City. N Eng J Med 2020; DOI: 10.1056/NEJMc2010419.
  • 43 Richardson S, Hirsch JS, Narasimhan M. et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020; DOI: 10.1001/jama.2020.6775.
  • 44 Novel Coronavirus Pneumonia Emergeny rResponse Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Chin J Epidemiol 2020; 41: 145-151
  • 45 Guo W, Li M, Dong Y. et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020; e3319
  • 46 Bode B, Garrett V, Messler J et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States glyctecsystems.com; 2020 [updated April 12, 2020; cited 2020 April 30]. Available from https://glytecsystems.com/wp-content/uploads/Sage.Glycemic-Characteristics-and-Clinical-Outcomes-of-Covid-19-Patients.FINAL_.pdf
  • 47 Wu Q, Zhou L, Sun X. et al. Altered lipid metabolism in recovered SARS patients twelve years after infection. Sci Rep 2017; 7: 9110
  • 48 Prevention CfDCa. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) (ONLINE). Online 2020 (March 15, 2020). Guidelines for COVID-19 management. Available from https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
  • 49 WHO Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected 2020 (cited 2020 March 15). Guidelines. Available at https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf
  • 50 Bornstein SR, Dalan R, Hopkins D. et al. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol 2020; DOI: 10.1038/s41574-020-0353-9.
  • 51 Marshall AC, Shaltout HA, Nautiyal M. et al. Fetal betamethasone exposure attenuates angiotensin-[1-7]-Mas receptor expression in the dorsal medulla of adult sheep. Peptides 2013; 44: 25-31
  • 52 Zhou YH, Qin YY, Lu YQ. et al. Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: Protocol of a randomized controlled trial. Chin Med J (Engl) 2020; 133: 1080-1086
  • 53 Association AD COVID-19 from the American Diabetes Association (Online). ADA; 2020 March 2020:Webpage9. Available from https://www.diabetes.org/diabetes/treatment-care/planning-sick-days/coronavirus
  • 54 AACE Position Statement: Coronavirus [COVID-19] and People with Diabetes (Updated March 18, 2020) (press release). Online: aace.com, March 18, 2020
  • 55 American College of Endocrinology L, Novo Nordisk, Medtronic. My Diabetes Emergency Plan. Online: mydiabetesememergencyplan.com; 2016
  • 56 Katulanda P, Dissanayake H, Ranathunga I. et al Prevention and management of COVID-19 among patients with diabetes: An appraisal of the literature. Diabetologia 2020; DOI: 10.1007/s00125-20-05164-x.
  • 57 Prevention CfDCa. Vaccine information for adults: Diabetes type 1 and 22016 March 18, 2020 (cited 2020 March 18). Available from https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/diabetes.html
  • 58 Smith SA, Poland GA. Influenza and pneumococcal immunization in diabetes. Diabetes Care 2004; 27 (Suppl 1): S111-S113
  • 59 Shah N. Higher co-infection rates in COVID19. Coronavirus (Internet). 2020 (cited 2020 March 18). Available from https://medium.com/@nigam/higher-co-infection-rates-in-covid19-b24965088333
  • 60 Mueller L. Buying Insulin in Canada Without a Prescription (BTC) (Electronic). Online2017 (updated September 1, 2017; cited 2020 March 18). Drug Commentary. Available from https://www.pharmacycheckerblog.com/buying-insulin-canada-without-prescription
  • 61 Tribble SJ You Can Buy Insulin Without A Prescription, But Should You? (Electronic). Online2015 (updated December 14, 2015; cited 2020 March 18). Health Guide. Available from https://www.npr.org/sections/health-shots/2015/12/14/459047328/you-can-buy-insulin-without-a-prescription-but-should-you
  • 62 PG Buying Insulin (India) (Internet). P G, editor. Online2007 October 11, 2007. (cited 2020 March 18, 2020). Available from https://www.indiamike.com/india/health-and-well-being-in-india-f2/buying-insulin-t44927/#post392426
  • 63 Fletcher F. Has anyone traveled to Mexico to buy their supplies? March 18. 2020 Ed OnlineForum.tudiabetes.org; 2017
  • 64 Association AD 13 Diabetes Care in the Hospital. Diabetes Care 2016; 39 (Suppl 1): S99
  • 65 Cansu DÜ, Korkmaz C. Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA. Rheumatology 2008; 47: 378-379
  • 66 Goyal V, Bordia A. The hypoglycemic effect of chloroquine. J Assoc Physicians India 1995; 43: 17-18
  • 67 Lee GA, Seneviratne T, Noor MA. et al. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS (London, England) 2004; 18: 641-649
  • 68 Hansen TK, Thiel S, Wouters PJ. et al. Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. J Clin Endocrinol Metab 2003; 88: 1082-1088
  • 69 Viby NE, Isidor MS, Buggeskov KB. et al. Glucagon-like peptide-1 [GLP-1] reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice. Endocrinology 2013; 154: 4503-4511
  • 70 Drucker DJ. Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications. Endocr Rev 2020; 41 pii: bnaa011 DOI: 10.1210/endrev/bnaa011.
  • 71 Zhou F, Zhang Y, Chen J. et al. Liraglutide attenuates lipopolysaccharide-induced acute lung injury in mice. Eur J Pharmacol 2016; 791: 735-740
  • 72 World B Retailers call for rationing of rubbing alcohol, hand sanitizer2020 March 18, 2020 (cited 2020 March 18). Available from https://www.msn.com/en-ph/money/topstories/retailers-call-for-rationing-of-rubbing-alcohol-hand-sanitizer/ar-BB112KyJ?li=BBr8Mkm
  • 73 Baker J. Extra insulin supplies, medications advised for people with diabetes in wake of COVID-19. Endocrine Today (Internet). 2020; (cited 2020 March 21). Available from https://www.healio.com/endocrinology/diabetes/news/online/%7B19b3e970-b54c-499b-8cfa-01591e7bcd6b%7D/extra-insulin-supplies-medications-advised-for-people-with-diabetes-in-wake-of-covid-19
  • 74 Administration UFaD Current and Resolved Drug Shortages and Discontinuations Reported to FDA 2020 (cited 2020 April 21). Available from https://www.accessdata.fda.gov/scripts/drugshortages/
  • 75 Society E COVID-10 Member Resources and Communications (Electronic). www.endocrine.org2020 (updated March 25, 2020; cited 2020 March 25). Available from https://www.endocrine.org/membership/covid-19-member-resources-and-communications
  • 76 Services CfMM President Trump Expands Telehealth Benefits for Medicare Beneficiaries During COVID-19 Outbreak. Online: CMS. 2020; March 17: 2020
  • 77 Ministry of Solidarity and Health F COVID-19 and telehealth: who can practice remotely and how? Online 2020 (updated March 31, 2020). Available from https://solidarites-sante.gouv.fr/soins-et-maladies/maladies/maladies-infectieuses/coronavirus/professionnels-de-sante/article/covid-19-et-telesante-qui-peut-pratiquer-a-distance-et-comment
  • 78 Singh MV, Chapleau MW, Harwani SC. et al. The immune system and hypertension. Immunol Res 2014; 59: 243-253
  • 79 Amador CA, Barrientos V, Pena J. et al. Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes. Hypertension 2014; 63: 797-803
  • 80 Kvakan H, Luft FC, Muller DN. Role of the immune system in hypertensive target organ damage. Trends Cardiovasc Med 2009; 19: 242-246
  • 81 Abboud FM, Harwani SC, Chapleau MW. Autonomic neural regulation of the immune system: implications for hypertension and cardiovascular disease. Hypertension 2012; 59: 755-762
  • 82 Guan W-j, Ni Z-y, Hu Y. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Eng J Med 2020; 382: 1708-1720
  • 83 Chen C, Chen C, Jiangtao Y. et al. Analysis of myocardial injury and cardiovascular diseases in critical patients with new Coronavirus pneumonia. Chin J Cardiovasc Dis. 2020 48.
  • 84 Guan W-j, Liang W-h, Zhao Y. et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A nationwide analysis. Eur Respir J 2020; 2000547
  • 85 Kabakov E, Norymberg C, Osher E. et al. Prevalence of hypertension in type 2 diabetes mellitus: impact of the tightening definition of high blood pressure and association with confounding risk factors. J Cardiometab Syndr 2006; 1: 95-101
  • 86 Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 2004; 25: 291-294
  • 87 Yan R, Zhang Y, Li Y. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020; 367: 1444
  • 88 Ramchand J, Patel SK, Kearney LG. et al. Plasma ACE2 activity predicts mortality in aortic stenosis and is associated with severe myocardial fibrosis. JACC Cardiovasc Imaging 2020; 13: 655-664
  • 89 Ferrario CM, Jessup J, Chappell MC. et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005; 111: 2605-2610
  • 90 Soler MJ, Ye M, Wysocki J. et al. Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan. Am J Physiol Renal Physiol 2009; 296: F398-F405
  • 91 Vuille-dit-Bille RN, Camargo SM, Emmenegger L. et al. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids 2015; 47: 693-705
  • 92 Burns KD, Lytvyn Y, Mahmud FH. et al. The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes. Am J Physiol Renal Physiol 2017; 312: F335-F342
  • 93 Gutta S, Grobe N, Kumbaji M. et al. Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes. Am J Physiol Renal Physiol 2018; 315: F263-F274
  • 94 Zheng YY, Ma YT, Zhang JY. et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020; 17: 259-260
  • 95 Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. Lancet Respir Med 2020; 8: e21. doi: 10.1016/S2213-2600(20)30116-8
  • 96 Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med 2020; pii: taaa041 doi. 10.1093/jtm/taaa041
  • 97 Imai Y, Kuba K, Rao S. et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436: 112-116
  • 98 South AM, Tomlinson L, Edmonston D. et al. Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic. Nat Rev Nephrol 2020; DOI: 10.1038/s41581-020-0279-4.
  • 99 Peiró C, Moncada S. Substituting Angiotensin-[1-7] to Prevent Lung Damage in SARSCoV2 Infection? Circulation 2020; doi: 10.1161/ CIRCULATIONAHA.120047297
  • 100 Kickbusch I, Leung G. Response to the emerging novel coronavirus outbreak. BMJ 2020; 368: m406
  • 101 Dalan R, Bornstein SR, El-Armouche A. et al. The ACE-2 in COVID-19: Foe or Friend?. Horm Metab Res 2020; DOI: 10.1055/a-1155-0501.
  • 102 Schiffrin EL, Flack JM, Ito S. et al. Hypertension and COVID-19. Am J Hypertens 2020; 33: 373-374
  • 103 Danser AHJ, Epstein M, Batlle D. Renin-Angiotensin System Blockers and the COVID-19 Pandemic. Hypertension. 2020 DOI: 10.1161/ HYPERTENSIONAHA.120.15082
  • 104 Sparks MA, South A, Welling P. et al. Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19. Clin J Am Soc Nephrol 2020; DOI: 10.2215/CJN.03530320.
  • 105 Vaduganathan M, Vardeny O, Michel T. et al. Renin–Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Eng J Med 2020; 382: 1653-1659
  • 106 Meng J, Xiao G, Zhang J. et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microb Infect 2020; 9: 757-760
  • 107 Zhang P, Zhu L, Cai J. et al. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020; DOI: 10.1161/CIRCRESAHA.120.317134.
  • 108 Cardiology ESf. Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers (Online). 2020 (updated March 13, 2020; cited 2020 March 15). Available from https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang
  • 109 Canada H Hypertension Canada’s Statement on: Hypertension, ACE-Inhibitors and Angiotensin Receptor Blockers and COVID-19 (Online). Online 2020 (cited 2020 March 17). Position statement]. Available from https://hypertension.ca/wp-content/uploads/2020/03/2020-30-15-Hypertension-Canada-Statement-on-COVID-19-ACEi-ARB.pdf
  • 110 Hypertension ISo A statement from the International Society of Hypertension on COVID-19 (Online). Online 2020 (updated March 16, 2020; cited 2020 March 17). Position Statement]. Available from: A statement from the International Society of Hypertension on COVID-19
  • 111 Hypertension ESo. Statement of the European Society of Hypertension (ESH) on hypertension, Renin Angiotensin System blockers and COVID-19 Online2020 (updated March 12, 2020; cited 2020 March 17). Position Statement. Available from https://www.eshonline.org/spotlights/esh-statement-on-covid-19/
  • 112 Cardiology AHAHFSoAACo. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician (Web). Online; 2020 (updated March 17, 2020; cited 2020 March 17). 1: (Position Statement). Available from https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician
  • 113 Li YP. Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a Treatment for patients with COVID-19 (Online). Online: clinicaltrials.gov. 2020;(updated February 27, 2020; cited 2020 March 15). Clinical trial registration. Available from https://clinicaltrials.gov/ct2/show/NCT04287686
  • 114 Aronson JK, Ferner RE. Drugs and the renin-angiotensin system in covid-19. BMJ 2020; 369: m1313
  • 115 Ellulu MS, Patimah I, Khaza’ai H. et al. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017; 13: 851-863
  • 116 Rodriguez-Hernandez H, Simental-Mendí LE, Rodgriguez-Ramirez G. et al. Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation. Int J Endocrinol 2013; 678159
  • 117 Ryan PM, Caplice NM. Is Adipose tissue a reservoir for viral spread, immune activation and cytokine amplification in COVID-19. Obesity 2020; DOI: 10.1002/oby.22843.
  • 118 Maier HE, Lopez R, Sanchez N. et al. Obesity increases the duration of influenza a virus shedding in adults. J Infect Dis 2018; 218: 1378-1382
  • 119 Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 2014; 222: R113-R127
  • 120 Choi J, Joseph L, Pilote L. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev 2013; 14: 232-244
  • 121 Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect. 2020; pii: S0399-077X(20)30086-X; doi: 10.1016/j. medmal.2020.03.007
  • 122 Luo X, Zhou W, Yan X et al. Prognostic value of C-reactive protein in patients with COVID-19. MedRxiv 2020; doi.org/10.1101/2020.03.21.20040360
  • 123 Trim W, Turner JE, Thompson D. Parallels in immunometabolic adipose tissue dysfunction with ageing and obesity. Front Immunol 2018; 9: 169
  • 124 Patel VB, Mori J, McLean BA. et al. ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes 2016; 65: 85-95
  • 125 Bloodworth MH, Rusznak M, Pfister CC. et al. Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus-induced type 2 responses and immunopathology. J Allergy Clin Immunol 2018; 142: e12
  • 126 Abdollahi M, Cushman M, Rosendaal FR. Obesity: Risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003; 89: 493-498
  • 127 Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118: 978-980
  • 128 Tang N, Bai H, Chen X. et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18: 1094-1099
  • 129 Stefan N, Birkenfeld AL, Schulze MB. et al. Obesity and impaired metabolic health in patients with COVID-19. Nat Rev Endocrinol 2020; DOI: 10.1038/s41574-020-0364-6.
  • 130 Sattar N, McInnes IB, McMurray JJV. Obesity a risk factor for severe COVID-19 infection: Multiple potential mechanisms. Circulation 2020; DOI: 10.1161/CIRCULATIONAHA.120.047659.
  • 131 Lighter J, Phillips M, Hochman S. et al. Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission. Clin Infect Dis 2020; DOI: 10.1093/cid/ciaa415.
  • 132 Moore BJB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368: 473-474
  • 133 Kang S, Tanaka T, Narazaki M. et al. Targeting interleukin-6 signaling in clinic. Immunity 2019; 50: 1007-1023
  • 134 Rockx B, Kuiken T, Herfst S. et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 2020; DOI: 10.1126/science.abb7314.
  • 135 Pradhan AD, Manson JE, Rifai N. et al. C-Reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327-334
  • 136 Pickup JC, Mattock MB, Chusney GD. et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40: 1286
  • 137 Hundhausen C, Roth A, Whalen E. et al. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med 2016; 8: 356ra119
  • 138 Chamarthi B, Williams GH, Ricchiuti V. et al. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans. Am J Hypertens 2011; 24: 1143-1148
  • 139 Luther JM, Gainer JV, Murphey LJ. et al. Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension 2006; 48: 1050-1057
  • 140 Smith GD, Lawlor DA, Harbord R. et al. Association of C-reactive protein with blood pressure and hypertension. Arterioscler Thromb Vasc Biol 2005; 25: 1051-1056
  • 141 Isidori AM, Pofi R, Hasenmajer V. et al. Use of glucocorticoids in patients with adrenal insufficiency and COVID-19 infection. Lancet Diabetes Endocrinol 2020; DOI: 10.1016/S2213-8587(20)30149-2.
  • 142 Endocrinology Sf. (webpage). Online2020 (updated March 11, 2020; cited 2020 March 15). Advice Statement. Available from https://www.endocrinology.org/news/item/14050/Coronavirus-advice-statement-for-patients-with-adrenal%2fpituitary-insufficiency
  • 143 Kaiser UB, Mirmira RG, Stewart PM. Our Response to COVID-19 as Endocrinologists and Diabetologists. J Clin Endocrinol Metab 2020; 105 pii: dgaa148 DOI: 10.1210/clinem/dgaa148.
  • 144 Irina B, Jon H, Vasileios C. et al. Primary adrenal insufficiency is associated with impaired natural killer cell function: A potential link to increased mortality. Eur J Endocrinol 2017; 176: 471-480
  • 145 Wiebke A, Stephanie EB, Simon HSP. et al. Endocrinology in the time of COVID-19: Management of adrenal insufficiency. Eur J Endocrinol 2020; DOI: 10.1530/EJE-20-0361.
  • 146 John N-P, Lynnette N, Martin R. et al. Endocrinology in the time of COVID-19: Management of Cushing’s syndrome. Eur J Endocrinol 2020; DOI: 10.1530/EJE-20-0352.
  • 147 Narayan SS, Lorenz K, Ukkat J. et al. Angiotensin converting enzymes ACE and ACE2 in thyroid cancer progression. Neoplasma 2019; 67: 402-409
  • 148 Diniz GP, Senger N, Carneiro-Ramos MS. et al. Cardiac ACE2/angiotensin 1-7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy. Ther Adv Cardiovasc Dis 2016; 10: 192-202
  • 149 Yao XH, Li TY, He ZC. et al. A pathological report of three COVID-19 cases by minimally invasive autopsies. Zhonghua Bing Li Xue Za Zhi 2020; 49: E009
  • 150 Zhang J-j, Dong X, Cao Y-y. et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China Allergy. 2020; DOI: 10.1111/all.14238.
  • 151 Channappanavar R, Fett C, Mack M. et al. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J Immunol 2017; 198: 4046-4053
  • 152 Christ-Crain M, Hoorn EJ, Sherlock M et al. Endocrinology in the time of COVID-19: Management of diabetes insipidus and hyponatraemia. Eur J Endocrinol 2020; EJE-20-0338: Accepted for publication: 24 Apr 2020
  • 153 Liamis G, Milionis HJ, Elisaf M. Hyponatremia in patients with infectious diseases. J Infect 2011; 63: 327-335
  • 154 Foundation NO Patients and Providers Fact Sheet: Injections or Infusions of Osteoporosis Medications During the COVID-19 Pandemic cdn.nof.org2020 (updated April 23, 2020; cited 2020 April 30). Available from https://cdn.nof.org/wp-content/uploads/NOF-COVID-Factsheet_.pdf
  • 155 Dyer O. Covid-19: Black people and other minorities are hardest hit in US. BMJ 2020; 369: m1483
  • 156 Yancy CW. COVID-19 and Afric an Americans. JAMA. 2020; doi: 10.1001ama.2020.6548
  • 157 Health LDoP Coronavirus [COVID-19]. Online: ldh.la.gov. 2020;
  • 158 Health Ndo Age adhusted rate of fatal lab confirmed COVID-19 cases per 100,000 by race/ethnicity group.online www.nyc.gov 2020
  • 159 Zhao Y, Zhao Z, Wang Y. et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv. 2020 DOI: 10.1101/2020.01.26.919985
  • 160 Cao Y, Li L, Feng Z. et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov 2020; 6: 11
  • 161 Asselta R, Paraboschi EM, Mantovani A et al. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. MedRxiv 2020; doi.org/101101/ 2020.03.30.20047878
  • 162 USTS. Report of the US Transgender Survey 2016 2015 [cited 2020 April 21]. Available from https://transequality.org/sites/default/files/docs/usts/USTS-Executive-Summary-Dec17.pdf
  • 163 Network NLC Transgender/Gender-Nonconforming People and Cance 2020 [cited 2020 April 21]. Available from https://cancer-network.org/cancer-information/transgendergender-nonconforming-people-and-cancer/
  • 164 Equality NCfT. The Coronavirus [COVID-19] Guide 2020 [cited 2020 April 21]. Available from https://transequality.org/covid19
  • 165 Shekhar S, Hannah-Shmouni F. Hookah smoking and COVID-19: Call for Action. CMAJ 2020; 192: E462
  • 166 Bauchner H, Golub RM, Zylke J. Editorial concern – Possible reporting of the same patients with COVID-19 in different reports. JAMA 2020; DOI: 10.1001/jama.2020.3980.