Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 24, Art. 66 (pp. 973-987)    |    2023       

»

Morphological study of the pancreatic and thyroid glands in patients II and III waves of covid-19 and molecular-biological analysis of the thyroid gland in the post-covid period

Vorobeva O.M.¹, Grigor'eva D.O.¹, Sterkhova K.A.¹, Ivanikha E.V.¹, Salov M.A.¹, Makarov I.A.¹, Pisareva M.M.², Mitrofanova Л.Б.¹

¹Almazov National Medical Research Centre, St. Petersburg
²Smorodintsev Research Institute of Influenza, St. Petersburg

Brief summary

In the modern literature there are data on the violation of carbohydrate metabolism and changes in the levels of thyroid hormones in patients in the post-covid period. The purpose of the study: to identify the defeat of the pancreatic and thyroid gland in patients with coronavirus infection. Materials and methods of research: histological examination of autopsy material and data from the history of 157 patients who died of COVID-19 in the 2nd and 3rd waves of the disease. Immunohistochemical study of 20 pancreatic fragments with antibodies to Spike SARS-CoV-2, ACE2, Insulin, CD26 (DPP 4) and 10 samples of thyroid gland with antibodies to: Spike SARS-CoV-2, ACE2, DPP4. Исследование поджелудочной глазе с выставление коктейлей ителе CD26/Insulin; ACE2/Insulin; Spike SARS-CoV-2/Insulin was administered to 2 patients. Results: Spike SARS-CoV-2 staining was detected in the endocrine (0-15% of cells) and exocrine part of the pancreas (less than 2% of cells). ACE2 and DPP4 were identified in the islets of Langerhans and the exocrine part of the pancreas in an average of less than 1% of cells. Потверждено базнение β-клеток гледудочной глаз (colocalization of insulin with Spike SARS-CoV-2, ACE2, DPP4 in the cytoplasm of cells). The staining of more than 90% of spike spike SARS-CoV-2 and DPP4, more than 60% - ACE2. No differences were identified in the defeat of the endocrine glands in patients with 2 and 3 waves of morbidity. When analyzing the clinical data, it was found that the dose of glucocorticosteroids (GCS) received by the patients of the 2nd wave was significantly higher compared to the patients of the 3rd wave (24mg/day and 16mg/day, respectively), and also revealed a moderate correlation of the maximum value of glucose with the maximum daily dozoi GKS in pereschete na dexamethasone (r=0.36). Conclusions: SARS-CoV-2 pancreatic and thyroid gland lesions were detected in patients with coronavirus infection. Diabetes mellitus types 1 and 2 develop significantly more often in patients after transmission of the coronavirus infection than in the general population. The pathogenesis of the defeat of the endocrine glands is multifactorial, at the moment it is difficult to determine whether there is a dominant factor or whether they have a combined influence.


Key words

pancreatic and thyroid glands, COVID-19 and post-covid period, immunohistochemical study and polymerase chain reaction

Reference list

1. Zhang, T., Mei, Q., Zhang, Z. et al. Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis. BMC Med 20, 444 (2022).


2. Rubino F, Amiel SA, Zimmet P, Alberti G, Bornstein S, Eckel RH, et al. New-onset diabetes in Covid-19. N Engl J Med. 2020;383:789-90.


3. Sathish T, Tapp RJ, Cooper ME, Zimmet P. Potential metabolic and inflammatory pathways between COVID-19 and new-onset diabetes. Diabetes Metab. 2021;47:101204.


4. Banerjee M, Pal R, Dutta S. Risk of incident diabetes post-COVID-19: a systematic review and meta-analysis. Prim Care Diabetes. 2022.


5. Rahmati M, Keshvari M, Mirnasuri S, Yon DK, Lee SW, Il Shin J, et al. The global impact of COVID-19 pandemic on the incidence of pediatric new-onset type 1 diabetes and ketoacidosis: a systematic review and meta-analysis. J Med Virol. 2022;94:5112-27.


6. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14:395-403.


7. Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr. 2020;14:535-45.


8. Guo L, Shi Z, Zhang Y, Wang C, Do Vale Moreira NC, Zuo H, et al. Comorbid diabetes and the risk of disease severity or death among 8807 COVID-19 patients in China: a meta-analysis. Diabetes Res Clin Pract. 2020;166:108346.


9. Rey-Reñones C, Martinez-Torres S, Martín-Luján FM, Pericas C, Redondo A, Vilaplana-Carnerero C, et al. Type 2 diabetes mellitus and COVID-19: a narrative review. Biomedicines. 2022;10:2089.


10. Wei L, Sun S, Xu CH, Zhang J, Xu Y, Zhu H, Peh SC, Korteweg C, McNutt MA, Gu J. Pathology of the thyroid in severe acute respiratory syndrome. Hum. Pathol. 2007;38(1):95-102.


11. Rotondi M., Coperchini F., Ricci G., Denegri M., et al. Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis. Journal of endocrinological investigation. 44(5), 1085−1090 (2021).


12. Lania A, Sandri MT, Cellini M, Mirani M, Lavezzi E, Mazziotti G. Thyrotoxicosis in patients with COVID-19: the THYRCOV study. Eur. J. Endocrinol. 2020;183(4):381-387. doi: 10.1530/eje-20-0335.


13. Brancatella A., Ricci D., Cappellani D., Viola N., et al. Is subacute thyroiditis an underestimated manifestation of SARS-CoV-2 infection? Insights from a case series. J. Clin. Endocrinol. Metabol. 105(10), e3742−e3746 (2020).


14. Pizzocaro A, Colombo P, Vena W, Ariano S, et al. Humanitas COVID-19 Task force. Outcome of Sars-COV-2-related thyrotoxicosis in survivors of Covid-19: a prospective study. Endocrine. 2021 Aug;73(2):255-260.


15. Barchuk A, Skougarevskiy D, Kouprianov A. et al. (2022) COVID-19 pandemic in Saint Petersburg, Russia: Combining population-based serological study and surveillance data. PLoS ONE 17(6): e0266945.


16. Millette K, Cuala J, Wang P, Marks C, et al. SARS-CoV2 infects pancreatic beta cells in vivo and induces cellular and subcellular disruptions that reflect beta cell dysfunction. Res Sq [Preprint]. 2021 Jul 20:rs.3.rs-592374.


17. Tang X, Uhl S, Zhang T, Xue D, et al. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab. 2021 Aug 3;33(8):1577-1591.e7.


18. Müller JA, Groß R, Conzelmann C, Krüger J, Merle U, Steinhart J, et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 2021;3(2):149-65


19. Santos R.A.S., Sampaio W.O., Alzamora A.C., Motta-Santos D., Alenina N., Bader M., Campagnole-Santos M.J. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7) Physiol. Rev. 2018;98:505-553.


20. Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z. ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2128-2130.e2. doi: 10.1016/j.cgh.2020.04.040. Epub 2020 Apr 22. PMID: 32334082; PMCID: PMC7194639.


21. Coate KC, Cha J, Shrestha S, Wang W, Gonçalves LM, Almaça J, et al. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells. Cell Metab. 2020;32(6):1028-40.e4.


22. Fignani D, Licata G, Brusco N, Nigi L, Grieco GE, Marselli L, et al. SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature. Frontiers in Endocrinology. 2020;11(876)


23. Solerte SB, Di Sabatino A, Galli M, Fiorina P. Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19. Acta Diabetol. 2020 Jul;57(7):779-783.


24. Lei Y, Hu L, Yang G, Piao L, Jin M, Cheng X. Dipeptidyl Peptidase-IV Inhibition for the Treatment of Cardiovascular Disease　- Recent Insights Focusing on Angiogenesis and Neovascularization. Circ J. 2017 May 25;81(6):770-776.


25. Mulvihill E.E., Drucker D.J. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr. Rev. 2014;35:992-1019.


26. Diaz-Jimenez D., Petrillo M.G., Busada J.T., Hermoso M.A., Cidlowski J.A. Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. J. Biol. Chem. 2020;295:3213-3227.


27. NIH COVID-19 Treatment Guidelines. [(accessed on 15 August 2022)]; Available online: https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/corticosteroids/


28. Sebastián-Martín A, Sánchez BG, Mora-Rodríguez JM, Bort A, Díaz-Laviada I. Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology. Biomedicines. 2022 Aug 19;10(8):2026.


29. Abramczyk U, Nowaczyński M, Słomczyński A, Wojnicz P, Zatyka P, Kuzan A. Consequences of COVID-19 for the Pancreas. Int J Mol Sci. 2022 Jan 13;23(2):864.


30. Taneera J., El-Huneidi W., Hamad M., Mohammed A.K., Elaraby E., Hachim M.Y. Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors. Biology. 2020;9:215.


31. Poma AM, Bonuccelli D, Giannini R, Macerola E, Vignali P, Ugolini C, Torregrossa L, Proietti A, Pistello M, Basolo A, Santini F, Toniolo A, Basolo F. COVID-19 autopsy cases: detection of virus in endocrine tissues. J Endocrinol Invest. 2022 Jan;45(1):209-214.


32. Yao XH, Li TY, He ZC, et al.. A pathological report of three COVID-19 cases by minimal invasive autopsies [article in Chinese]. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411-417.


33. Chen W, Tian Y, Li Z, Zhu J, Wei T, Lei J. Potential Interaction Between SARS-CoV-2 and Thyroid: A Review. Endocrinology. 2021 Mar 1;162(3):bqab004.


34. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846-848.


35. Barton LM, Duval EJ, Stroberg E, Ghosh S, Mukhopadhyay S. COVID-19 autopsies, Oklahoma, USA. Am J Clin Pathol. 2020;153(6):725-733.


36. Rotondi M, Coperchini F, Ricci G, et al.. Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis. J Endocrinol Invest. Published October 6, 2020. doi:10.1007/s40618-020-01436-w


37. Ozóg J, Jarzab M, Pawlaczek A, Oczko-Wojciechowska M, Włoch J, Roskosz J, Gubała E. Ekspresja genu DPP4 w raku brodawkowatym tarczycy [Expression of DPP4 gene in papillary thyroid carcinoma]. Endokrynol Pol. 2006;57 Suppl A:12-7.