Sukhminder Jit Singh Bajwa
Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Banur, Patiala,Punjab, India
Ridhima Sharma
Superspeciality Paediatric hospital and Postgraduate teaching institute, Noida, Uttar Pradesh, India
Madhuri S Kurdi
Karnataka Institute Of Medical Sciences(KIMS), Hubli, Karnataka, India
Severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) has affected millions of people across the world engendering an unprecedented pandemic. Coronavirus disease (COVID)-19 can present asymptomatic or in the form of the acute respiratory syndrome, viral pneumonia,or sepsis. Due to the novelty of the disease, the endocrine manifestations are not fully understood. It becomes indispensable to address the underlying endocrine disruptions contributing to the severe form of illness and thereby increasing the mortality.We discuss here the SARS-CoV-2 virus and endocrine reverberations based on the research with structurally similar SARS-COV-1. SARS-CoV-2 enters the body via its attachment to the angiotensin-converting enzyme 2 (ACE2) receptors. Apart from lungs,ACE2 expression on various organs can lead to endocrine perturbations.In COVID-19 infection, pre-existing endocrine disorders warrant cautious management and may require replacement therapy. COVID-19 and its repercussions on hormones are discussed extensively in this review.
[1] Téblick A, Peeters B, Langouche L, Van den,Berghe G. Adrenal function and dysfunction in critically ill patients. Nat Rev Endocrinol, 2019, 15: 417-427.
[2] Khoo B, Boshier PR, Freethy A,Tharakan G, Saeed S,Hill N. et al. Redefining the stress cortisol response to surgery. Clin Endocrinol (Oxf), 2017, 87: 451-58.
[3] Alves C, Casqueiro J, Casqueiro J. Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J Endocrinol Metab, 2012, 16: 27.
[4] Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes MetabSyndr, 2020,14: 211-2.
[5] Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV. Viruses, 2020, 12: 135.DOI:10.3390/v12020135
[6] Phan T. Novel coronavirus from discovery to clinical diagnostics. Infect Genet Evol., 2020, 79:104211.
[7] de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol., 2016, 14: 523-534.
[8] Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol., 2020, 79: 104212.
[9] Chen L, Liu W, Zhang Q, Xu K, Ye G, Wu W, et al. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. EmergMicrob Infect,2020, 9: 313-319.
[10] Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020.DOI:10.1038/s41586-020-2012-7
[11] Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis.J Med Virol 2020, 92: 418-423.
[12] Du Y, Tu L, Zhu P, Wang R, Yang P, Wang X, et al.Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med., 2020,201(11):1372-1379.
[13] Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol., 2020, 92(7): 791-796.
[14] Channappanavar R., Zhao J., Perlman S. T cell-mediated immune response to respiratory coronaviruses. Journal, 2014, 59: 118-128.
[15] Rabi F.A., Al Zoubi M.S., Kasasbeh G.A., Salameh D.M., Al-Nasser A.D. SARS-CoV-2 and Coronavirus disease 2019: what we know so far. Journal, 2020,9(3): 231.
[16] Chang L, Yan Y, Wang L. Coronavirus disease 2019:coronaviruses and blood safety. Transfus Med Rev.,2020, 34:,75-80
[17] Liu F, Long X, Zou W, Fang M, Wu W, Li W, et al.Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection.MedRxiv, 2020.DOI:10.1101/2020.02.28.20029181
[18] Leow MK-S, Kwek DS-K, Ng AW-K, Ong K-C,Kaw GJ-L, Lee LS-U. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clin Endocrinol., 2005, 63:197-202.
[19] Pal R, Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. J Endocrinol Invest, 2020, 43(7): 1027-1031.DOI: 10.1007/s40618-020-01276-8
[20] Kaiser UB, Mirmira RG, Stewart PM. Our Response to COVID-19 as Endocrinologists and Diabetologists. J Clin Endocrinol Metab, 2020, 105(5):dgaa148.DOI:10.1210/clinem/dgaa148. PMID: 32232480;PMCID:PMC7108679
[21] Nataf S. An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19. J Med Virol., 2020, 92: 1743-1744.
[22] Wei L, Sun S, Zhang J, Zhu H, Xu Y, Ma Q et al. Endocrine cells of the adenohypophysis in severe acute respiratory syndrome (SARS). Biochem Cell Biol.,2010, 88: 723-30.
[23] Agarwal S, Agarwal SK. Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV.Postgraduate Medical Journal, 2020, 96: 412-416.
[24] Leow MK, Kwek DS, Ng AW, Ong KC, Kaw GJ,Lee LS. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clin Endocrinol (Oxf),2005, 63: 197-202.
[25] Vladutiu GD, Natelson BH. Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Muscle Nerve,2004, 30: 38-43.
[26] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen 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: 271-280.
[27] Sriramula S, Xia H, Xu P, Lazartigues E. Brain-targeted angiotensin-converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-mediated inflammation. Hypertension, 2015, 65(3): 577-586.
[28] Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of ncephalitis in mice transgenic for human ACE2. J Virol., 2008, 82(15): 7264-7275.
[29] Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome?Rhinology, 2020, 58: 299-301.
[30] Vilar L, Abucham J, Albuquerque JL, Aroujo LA,Aevedo MF, Boguszewski CL, et al. Controversial issues in the management of hyperprolactinemia and prolactinomas - an overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab,2018, 62: 236-263.
[31] Vardas K, Apostolou K, Briassouli E,Goukos D,Psarra K, Botoula E. et al. Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS. Biomed Res Int., 2014, 2014: 803561.
[32] Tasker RC, Roe MF, Bloxham DM, White DK,Ross-Russell RI, O’Donnell DR. The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.Intensive Care Med., 2004, 30: 2257-2262.
[33] Wang W, Ye Y, Yao H. Evaluation and observation of serum thyroid hormone and parathyroid hormone in patients with severe acute respiratory syndrome. J Chin Antituberculous Assoc., 2003, 25:232-234.
[34] Chen T, Wu D, Chen H, Yan W, Yang D, Chen G,Ma Ke, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ2020; 368: m1295
[35] Jonklaas J, Bianco AC, Bauer AJ,Burman KD, Cappola AR, Celi FS.et al. American Thyroid Association Task Force on Thyroid Hormone Replacement.Guidelines for the treatment of hypothyroidism:prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid,2014, 24: 1670-1751.
[36] Pal R, Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. Journal of Endocrinological Investigation, 2020, 43: 1027-1031.
[37] Wei L, Sun S, Xu C, Zhang J, Xu Y, Zhu H, et al.Pathology of the thyroid in severe acute respiratory syndrome. Hum Pathol, 2007, 38: 95-102.
[38] Wheatland R. Molecular mimicry of ACTH in SARS-implications for corticosteroid treatment and prophylaxis. Med Hypotheses, 2004, 63: 855-862.
[39] Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J.et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol.,2003, 200: 282-9.
[40] Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses, 2020, 12:244.
[41] Pal R, Bhansali A. COVID-19, diabetes mellitus and ACE2: the conundrum. Diabetes Res Clin Pract,2020, 162: 108132.
[42] Yang J-K, Lin S-S, Ji X-J,Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol, 2010, 47: 193-9.
[43] Yang J-K, Lin S-S, Ji X-J, Guo L-M. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol., 2010, 47: 193-199.
[44] Richard C, Wadowski M, Goruk S, Cameron L, Sharma AM, Field CJ. Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res Care, 2017, 5(1):e000379.DOI:10.1136/bmjdrc-2016-000379
[45] Yang JK, Feng Y, Yuan MY,Yuan SY, Fu HJ, Wu BY. et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med., 2006, 23:623-8.
[46] Pal R, Bhansali A. COVID-19, diabetes mellitus and ACE2: the conundrum. Diabetes Res Clin Pract,2020, 162: 108132.
[47] Lang Z, Zhang L, Zhang S,, Meng X, Li J, Song C.et al. Pathological study on severe acute respiratory syndrome. Chin Med J (Engl), 2003, 116: 976-980.
[48] Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. BiochemBiophys Res Commun, 2020.DOI: 10.1016/j.bbrc.2020.02.071
[49] Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett, 2002, 532: 107-110.
[50] Wang Z, Xu X. scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells, 2020, 9(4): 90.DOI:10.3390/cells9040920
[51] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen 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: 271-280.e8 DOI: 10.1016/j.cell.2020.02.052
[52] Ma L, Xie W, Li D, Shi L, Mao Y, Xiong Y, et al.Effect of SARS-CoV-2 infection upon male gonadal function: a single center-based study. MedRxiv, 2020 DOI:https://doi.org/10.1101/2020.03.21.20037267(Last accessed on 14 Nov 2020)
[53] Xu J, Qi L, Chi X, Yang J, Wei X, Gong E. et al.Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod, 2006, 74: 410-416.
[54] Kyrou I, Karteris E., Robbins T, Chatha K, Drenos F, Randeva HS. Polycystic ovary syndrome (PCOS) and COVID-19: an overlooked female patient population at potentially higher risk during the COVID-19 pandemic. BMC Med., 2020, 18: 220.DOI:https://doi.org/10.1186/s12916-020-01697-5
[55] Santos R, Sampaio W, Alzamora A, Motta-Santos D, Alenina N, Bader M, et al. The ACE2/angiotensin-(1-7)/MAS axis of the renin-angiotensin system:focus on angiotensin-(1-7). Physiol Rev., 2018, 98:505-53.
[56] Keidar S, Kaplan M, Gamliel-Lazarovich A. ACE2 of the heart: from angiotensin I to angiotensin (1-7).Cardiovasc Res., 2007, 73: 463-9.
[57] Barbaro NR, Fontana V, Modolo R, De Faria AP,Sabbatini AR, Fonseca F, et al. Increased arterial stiffness in resistant hypertension is associated with inflammatory biomarkers. Blood Press, 2015, 24:7-13.
[58] Marshall RP, Webb S, Bellingan GJ, Montgomery HE, Chaudhari B, McAnulty RJ, et al.Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am J Respir Crit Care Med., 2002, 166: 646-50.
[59] Cruces P, Díaz F, Puga A, Erranz B, Donoso A, Carvajal C, et al. Angiotensin-converting enzyme insertion/deletion polymorphism is associated with severe hypoxemia in pediatric ARDS. Intensive Care Med.,2012, 38: 113-9.
[60] Jia H. Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock,2016,46: 239-48.
[61] Feng Y, Wan H, Liu J, Zhang R, Ma Q, Han B, et al. The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in nonsmall cell lung cancer. Oncol Rep., 2010, 23:941-8.
[62] Santos R, Sampaio W, Alzamora A, Motta-Santos D, Alenina N, Bader M, et al. The ACE2/angiotensin-(1-7)/MAS axis of the renin-angiotensin system:focus on angiotensin-(1-7). Physiol Rev., 2018, 98:505-53.
[63] Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H. Tissue distribution of ACE2 protein,the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol.,2004, 203: 631-7.
[64] Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, 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, 8: 475-81.
[65] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet, 2020, 395:507-13.
[66] Zhou Y, Frey TK, Yang JJ. Viral calciomics: interplays between Ca2+ and virus. Cell Calcium,2009,46(1): 1-17.
[67] Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA, 2003,289: 2801-9.
[68] Bossoni S, Chiesa L, Giustina A. Severe hypocalcemia in a thyroidectomized woman with Covid-19 infection. Endocrine [Internet]. 2020 [cited 2020 May 21]; Available from:http://link. springer.com/10.1007/s12020-020-02326-088
[69] Sassi F, Tamone C, D’amelio P. Vitamin D: nutrient,hormone, and immunomodulator. Nutrients,2018,10(11): 1656.
[70] Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients, 2013, 5(7):2502-2521.
Aims and Scope