Metabolic and Endocrine Complications of Long-COVID-19: A Review

Abstract

Over the past two years, the outbreak of coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has centralized the interest of the health care systems and the scientific world. The majority of COVID-19-infected individuals recover fully. However, about 12–50% of patients experience various mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or 'long-COVID'. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global healthcare challenge. This review article discusses the possible metabolic and endocrine complications of long-COVID and the relevant research findings.

Key words

long-COVID-19 - chronic COVID - post COVID-19 syndrome - metabolic - endocrine - effects of long-COVID

Publication History

Received: 12 December 2022
Received: 28 February 2023

Accepted: 27 March 2023

Accepted Manuscript online:
28 March 2023

Article published online:
17 May 2023

• References

• 1 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
• 2 Gupta A, Madhavan MV, Sehgal K. et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26: 1017-1032
• 3 Ackermann M, Verleden SE, Kuehnel M. et al. pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;
• 4 Centers for Disease Control and Prevention, Post-COVID Conditions www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html. (Last visited August 15, 2022)
• 5 The Centers for Disease Control and Prevention also recognizes other post-COVID conditions, a series of illnesses resulting in debilitating conditions, that can be similar to long-COVID. See Centers for Disease Control and Prevention, Post-COVID Conditions www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html (Last visited August 15, 2022)
• 6 World Health Organization (2022). WHO Coronavirus Dashboard https://covid19.who.int/. (Last visited August 25 2022)
• 7 Bornstein SR, Cozma D, Kamel M. et al. Long-COVID, metabolic and endocrine disease. Horm Metab Res 2022; 54: 562-566
• 8 World Health Organization 2022. Coronavirus disease (COVID-19): Post COVID-19 condition https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-post-covid-19-condition. (Last visited August 15, 2022)
• 9 Soriano JB, Murthy S, Marshall JC. et. al. WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022; 22: e102-e107
• 10 Chen C, Haupert SR, Zimmermann L et. al. Global prevalence of post COVID-19 condition or long COVID: A meta-analysis and systematic review. J Infect Dis 2022; JIAC: 136. doi: 10.1093/infdis/jiac136
• 11 Peluso MJ, Deveau TM, Munter SE et al. Impact of pre-existing chronic viral infection and reactivation on the development of long COVID. medRxiv [Preprint] 2022: 2022.06.21.22276660. doi: 10.1101/2022.06.21.22276660. Update in: J Clin Invest 2022; PMID: 35898346; PMCID: PMC9327632
• 12 Zubchenko S, Kril I, Nadizhko O. et al. Herpesvirus infections and post-COVID-19 manifestations: A pilot observational study. Rheumatol Int 2022; 42: 1523-1530
• 13 Su Y, Yuan D, Chen DG. et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022; 185: 881-895.e20
• 14 Castanares-Zapatero D, Kohn L, Dauvrin M et al. Long COVID: Pathophysiology – epidemiology and patient needs – Synthesis. Health Services Research (HSR) Brussels: Belgian Health Care Knowledge Centre (KCE). 2021. KCE Reports 344Cs. D/2021/10.273/30
• 15 Castanares-Zapatero D, Chalon P, Kohn L. et al. Pathophysiology and mechanism of long COVID: A comprehensive review. Ann Med 2022; 54: 1473-1487
• 16 Sudre CH, Murray B, Varsavsky T. et al. Attributes and predictors of long COVID. Nat Med 2021; 27: 626-631
• 17 Long QX, Tang XJ, Shi QL. et al. Clinical and immunological assessment of asymptomatic SARSCoV-2 infections. Nat Med 2020; 26: 1200-1204
• 18 Akbarialiabad H, Taghrir MH, Abdollahi A. et al. Long COVID, a comprehensive systematic scoping review. Infection 2021; 49: 1163-1186
• 19 Baig AM. Deleterious outcomes in long-hauler COVID-19: The effects of SARS-CoV-2 on the CNS in chronic COVID syndrome. ACS Chem Neurosci 2020; 11: 4017-4020
• 20 Giuseppe F, Francesca F, Tambelli R. et al. COVID-19 pandemic in the Italian population: Validation of a post-traumatic stress disorder questionnaire and prevalence of PTSD symptomatology. Int J Environ Res Public Health 2020; 17: 415
• 21 Jiang H-J, Nan J, Lv Z. et al. Psychological impacts of the COVID-19 epidemic on Chinese people: Exposure, post-traumatic stress symptom, and emotion regulation. Asian Pac J Trop Med 2020; 13: 252-259
• 22 Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun 2020; 87: 34-39
• 23 Wijeratne T, Crewther S. COVID-19 and long-term neurological problems: Challenges ahead with post-COVID-19 neurological syndrome. Aust J Gen Pract 2021; 50
• 24 Walker KA, Windham BG, Power MC. et al. The association of mid-to late-life systemic inflammation with white matter structure in older adults: The atherosclerosis risk in communities study. Neurobiol Aging 2018; 68: 26-33
• 25 Walker KA, Hoogeveen RC, Folsom AR. et al. Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology 2017; 89: 2262-2270
• 26 Higgins V, Sohaei D, Diamandis EP. et al. COVID-19: From an acute to chronic disease? Potential long-term health consequences. Crit Rev Clin Lab Sci 2020; 58: 297-310
• 27 Puchner B, Sahanic S, Kirchmair R. et al. Beneficial effects of multi-disciplinary rehabilitation in post-acute COVID-19-an observational cohort study. Eur J Phys Rehabil Med 2021; 57: 189-198
• 28 Tejera D, Mercan D, Sanchez-Caro JM. et al. Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome. EMBO J 2019; 38: e101064
• 29 He X-F, Xu J, Li G. et al. NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer's disease. Cell Death Dis 2020; 11: 849
• 30 Scherer PE, Kirwan JP, Rosen CJ. Post-acute sequelae of COVID-19: A metabolic perspective. eLife 2022; 11: e78200
• 31 Leong A, Cole J, Brenner LN. et al. Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis. Epidemiology (Cambridge, Mass.) 2020; 18: e1003553
• 32 Vimercati L, De Maria L, Quarato M. et al. Association between long COVID and overweight/obesity. J Clin Med 2021; 10: 4143
• 33 Peters SAE, MacMahon S, Woodward M. Obesity as a risk factor for COVID-19 mortality in women and men in the UK biobank: Comparisons with influenza/pneumonia and coronary heart disease. Diabetes Obes Metab 2021; 23: 258-262
• 34 Ritter A, Kreis NN, Louwen F. et al. Obesity and COVID-19: Molecular mechanisms linking both pandemics. Int J Mol Sci 2020; 21: 5793
• 35 Kazakou P, Paschou SA, Psaltopoulou T. et al. Early and late endocrine complications of COVID-19. Endocr Connect 2021; 10: R229-R239
• 36 Diabetes UK, Exploring research: Can coronavirus cause diabetes? 2022 https://www.diabetes.org.uk/about_us/news/new-worse-cases-coronavirus#:~:text=Studies%20from%20the%20UK%2C%20the,haven't%20had%20the%20virus
• 37 Steenblock C, Schwarz PEH, Ludwig B. et al. COVID-19 and metabolic disease: Mechanisms and clinical management. Lancet Diabetes Endocrinol 2021; 9: 786-798
• 38 Montefusco L, Ben Nasr M, D'Addio F. et al. Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab 2021; 3: 774-785
• 39 Rezaei A, Neshat S, Heshmat-Ghahdarijani K. Alterations of lipid profile in COVID-19: A narrative review. Curr Probl Cardiol 2022; 47: 100907
• 40 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
• 41 Ding Y, He L, Zhang Q. et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARSCoV) in SARS patients: Implications for pathogenesis and virus transmission pathways. J Pathol 2004; 203: 622-630
• 42 Laura MM, Federica B. et al. Possible long-term endocrine-metabolic complications in COVID-19: Lesson from the SARS model. Endocrine 2020; 68: 467-470
• 43 Eroglu I, Eroglu BC, Guven GS. Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19). Nutrition 2021; 90: 111308
• 44 Clarke SA, Abbara A, Dhillo WS. Impact of COVID-19 on the endocrine system: A mini-review. Endocrinology 2022; 163: bqab203
• 45 Bansal R, Gubbi S, Koch CA. COVID-19 and chronic fatigue syndrome: An endocrine perspective. J Clin Transl Endocrinol 2022; 27: 100284
• 46 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; 36: e3319
• 47 Hanley B, Naresh KN, Roufosse C. et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: A post-mortem study. Lancet Microbe 2020; 1: e245-e253
• 48 Lania A, Sandri M, Cellini M. et al. Thyrotoxicosis in patients with COVID-19: The THYRCOV study. Eur J Endocrinol 2020; 183: 381-387
• 49 Khoo B, Tan T, Clarke S. et al. Thyroid function before, during, and after COVID-19. J Clin Endocrinol Metab 2020; 106: e803-e811
• 50 Mung SM, Jude EB. Interplay between endocrinology, metabolism and COVID-19 infection. Clin Med (Lond) 2021; 21: e499-e504
• 51 Chen M, Zhou W, Xu W. Thyroid function analysis in 50 patients with COVID-19: A retrospective study. Thyroid 2021; 31: 8-11
• 52 Mussa B, Srivastava A, Verberne A. COVID-19 and neurological impairment: Hypothalamic circuits and beyond. Viruses 2021; 13: 498
• 53 Leyendecker P, Ritter S, Riou M. et al. Acute adrenal infarction as an incidental CT finding and a potential prognosis factor in severe SARS-CoV-2 infection: A retrospective cohort analysis on 219 patients. Eur Radiol 2021; 31: 895-900
• 54 Kanczkowski W, Evert K, Stadtmuller M. et al. COVID-19 targets human adrenal glands. Lancet Diabetes Endocrinol 2022; 10: 13-16
• 55 Swart R, Hoorn E, Betjes M. et al. Hyponatremia and inflammation: The emerging role of interleukin-6 in osmoregulation. Nephron Physiol 2011; 118: 45-51
• 56 Rastrelli G, Di Stasi V, Inglese F. et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology 2020; 9: 88-98
• 57 Holtmann N, Edimiris P, Andree M. et al. Assessment of SARS-CoV-2 in human semen – a cohort study. Fertil Steril 2020; 114: 233-238
• 58 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: 920
• 59 Mannur S, Jabeen T, Khader MA. et al. Post-COVID-19-associated decline in long-term male fertility and embryo quality during assisted reproductive technology. QJM 2021; 114: 328-330
• 60 Li D, Jin M, Bao P. et al. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open 2020; 3: e208292
• 61 Reis FM, Bouissou DR, Pereira VM. et al. Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil Steril 2011; 95: 176-181
• 62 Phelan N, Behan LA, Owens L. The impact of the COVID-19 pandemic on women's reproductive health. Front Endocrinol (Lausanne) 2021; 12: 642755
• 63 Li F, Lu H, Zhang Q. et al. Impact of COVID-19 on female fertility: A systematic review and meta-analysis protocol. BMJ Open 2021; 11: e045524