Review Article

A Comprehensive Review of COVID-19–Associated Endocrine Manifestations

Authors: Saif Khan, MD, Maryam Karim, MBBS, Vasu Gupta, MBBS, Heenam Goel, MBBS, Rohit Jain, MD

Abstract

Coronavirus disease 2019 (COVID-19) has played a significant part in systematic damage, affecting lives and leading to significant mortality. The endocrine system is one of the systems affected by this pandemic outbreak. The relationship between them has been identified in previous and ongoing research. The mechanism through which severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can achieve this is similar to that for organs that express angiotensin-converting enzyme 2 receptors, which is the primary binding site of the virus. Endocrine cells widely express angiotensin-converting enzyme 2 receptors and transmembrane serine protease 2, the primary mediators initiating the acute phase of the disease. This review aimed to identify and discuss the endocrine complications of COVID-19. This primary focus is on presenting thyroid disorders or newly diagnosed diabetes mellitus (DM). Thyroid dysfunction with subacute thyroiditis, Graves’ disease, and hypothyroidism caused by primary autoimmune thyroiditis has been reported. Pancreatic damage leads to type 1 DM because of the autoimmune nature of the disease and type 2 DM because of postinflammatory insulin resistance. Because follow-up data on COVID-19 on the endocrine glands are limited, long-term investigations are needed to assess specific effects.

 
Posted in: Endocrinology, Diabetes, and Metabolism40 Infectious Disease143

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References

1. World Health Organization. WHO coronavirus (COVID-19) dashboard. https://covid19.who.int/. Accessed January 17, 2023.
 
2. V’kovski P, Kratzel A, Steiner S, et al. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 2020;19:155–170.
 
3. Ranga U. SARS-CoV-2 aerosol and droplets: an overview. VirusDisease 2021;32:190–197.
 
4. Viner RM, Ward JL, Hudson LD, et al. Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents. Arch Dis Child 2021;106:802–807.
 
5. Carfì A, Bernabei R, Landi F, et al. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603–605.
 
6. Abdel-Moneim A, Hosni A. Insights into the possible impact of COVID-19 on the endocrine system. Arch Physiol Biochem 2021 March 3:1–9 [online ahead of print] .
 
7. Soldevila B, Puig-Domingo M, Marazuela M, et al. Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated? Rev Endocr Metab Disord 2021;23:137–150.
 
8. Huang BZ, Sidell MA, Wu BU, et al. Pre-existing pancreatitis and elevated risks of COVID-19 severity and mortality. Gastroenterology 2022;162: 1758-1760.e3.
 
9. Patel HK, Makker J, Alemam A, et al. Diarrhea due to SARS-CoV-2-related exocrine pancreatic insufficiency. Case Rep Gastrointest Med 2021;2021:1–5.
 
10. Unsworth R, Wallace S, Oliver NS, et al. New-onset type 1 diabetes in children during COVID-19: multicenter regional findings in the U.K. Diabetes Care 2020;43:e170–e171.
 
11. Wang MY, Zhao R, Gao LJ, et al. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol 2020; 10:587269.
 
12. Yang J, Petitjean SJL, Koehler M, et al. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat Commun 2021;12:2996.
 
13. Sriram K, Insel PA. A hypothesis for pathobiology and treatment of COVID-19: the centrality of ACE1/ACE2 imbalance. Br J Pharmacol 2020;177:4825–4844.
 
14. Lim S, Bae JH, Kwon HS, et al. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol 2020;17:11–30.
 
15. Santos A, Magro DO, Evangelista-Poderoso R, et al. Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications. Diabetol Metab Syndr 2021;13:23.
 
16. Nader D, Fletcher N, Curley GF, et al. SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19. PLOS One 2021;16:e0253347.
 
17. Davis PJ, Lin HY, Hercbergs A, et al. Coronaviruses and integrin αvβ3: does thyroid hormone modify the relationship? Endocr Res 2020;45:210–215.
 
18. Lisco G, de Tullio A, Jirillo E, et al. Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects. J Endocrinol Invest 2021;44:1801–1814.
 
19. Shekhar S, Wurth R, Kamilaris CDC, et al. Endocrine conditions and COVID-19. Horm Metab Res 2020;52:471–484.
 
20. Landstra CP, de Koning EJP. COVID-19 and diabetes: understanding the interrelationship and risks for a severe course. Front Endocrinol 2021;12:599.
 
21. Müller JA, Groß R, Conzelmann C, et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab 2021;3: 149–165.
 
22. Sun B, Huang S, Zhou J, et al. Perspectives of antidiabetic drugs in diabetes with coronavirus infections. Front Pharmacol 2021;11:592439.
 
23. Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol 2022;10:311–321.
 
24. d’Annunzio G, Bassi M, de Rose EL, et al. Increased frequency of diabetic ketoacidosis: the link with COVID-19 pandemic. Front Clin Diabetes Healthc 2022;3:846827.
 
25. Sherwani SI, Khan HA, Ekhzaimy A, et al. Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark Insights 2016;11: 95–104.
 
26. Breton MD, Patek SD, Lv D, et al. Continuous glucose monitoring and insulin informed advisory system with automated titration and dosing of insulin reduces glucose variability in type 1 diabetes mellitus. Diabetes Technol Ther 2018;20:531–540.
 
27. Cromer SJ, Colling C, Schatoff D, et al. Newly diagnosed diabetes vs. pre-existing diabetes upon admission for COVID-19: associated factors, short-term outcomes, and long-term glycemic phenotypes. J Diabetes Complications 2022;36:108145.
 
28. Giovanella L, Ruggeri RM, Ovčariček PP, et al. Prevalence of thyroid dysfunction in patients with COVID-19: a systematic review. Clin Transl Imaging 2021;9:233–240.
 
29. Lania A, Sandri MT, Cellini M, et al. Thyrotoxicosis in patients with COVID-19: the THYRCOV study. Eur J Endocrinol 2020;183: 381–387.
 
30. Chen M, Zhou W, Xu W, et al. Thyroid function analysis in 50 patients with COVID-19: a retrospective study. Thyroid 2021;31:8–11.
 
31. Naguib R. Potential relationships between COVID-19 and the thyroid gland: an update J Int Med Res 2022;50:3000605221082898.
 
32. Khoo B, Tan T, Clarke SA, et al. Thyroid function before, during, and after COVID-19. J Clin Endocrinol Metab 2021;106:E803–E811.
 
33. Scappaticcio L, Pitoia F, Esposito K, et al. Impact of COVID-19 on the thyroid gland: an update. Rev Endocr Metab Disord 2021;22:803–815.
 
34. Muller I, Cannavaro D, Dazzi D, et al. SARS-CoV-2-related atypical thyroiditis. Lancet Diabetes Endocrinol 2020;8:739–741.
 
35. Martins JRM, Villagelin DGP, Carvalho GA, et al. Management of thyroid disorders during the COVID-19 outbreak: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM). Arch Endocrinol Metab 2021;65:368–375.
 
36. Burekovic A, Halilovic D, Sahbaz A, et al. Hypothyroidism and subclinical hypothyroidism as a consequence of COVID-19 infection. Med Arch 2022; 76:12–16.
 
37. Gaitonde DY, Rowley KD, Sweeney LB, et al. Hypothyroidism: an update. Am Family Physician 2012;86:244–251.
 
38. Pramono LA. COVID-19 and thyroid diseases: how the pandemic situation affects thyroid disease patients. J ASEAN Fed Endocr Soc 2020;35:155–157.
 
39. Chopra IJ. Euthyroid sick syndrome: is it a misnomer? J Clin Endocrinol Metab 1997;82:329–334.
 
40. Campi I, Bulgarelli I, Dubini A, et al. The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection. Eur J Endocrinol 2021; 184(5):699–709.
 
41. Zou R, Wu C, Zhang S, et al. Euthyroid sick syndrome in patients with COVID-19. Front Endocrinol 2020;11:566439.
 
42. Inaba H, Aizawa T. Coronavirus disease 2019 and the thyroid—progress and perspectives. Front Endocrinol 2021;12:708333.
 
43. Li H, Tian S, Chen T, et al. Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19. Diabetes Obes Metab 2020;22:1897–1906.
 
44. Lampasona V, Secchi M, Scavini M, et al. Antibody response to multiple antigens of SARS-CoV-2 in patients with diabetes: an observational cohort study. Diabetologia 2020;63:2548–2558.