Журналов:     Статей:        

Судебная медицина. 2020; 6: 8-30

ПАТОЛОГИЧЕСКАЯ АНАТОМИЯ ИНФЕКЦИИ, ВЫЗВАННОЙ SARS-COV-2

Коган Е. А., Березовский Ю. С., Проценко Д. Д., Багдасарян Т. Р., Грецов Е. М., Демура С. А., Демяшкин Г. А., Калинин Д. В., Куклева А. Д., Курилина Э. В., Некрасова Т. П., Парамонова Н. Б., Пономарев А. Б., Раденска-Лоповок С. Г., Семенова Л. А., Тертычный А. С.

https://doi.org/10.19048/2411-8729-2020-6-2-8-30

Аннотация

Материалом для исследования послужили данные 80 аутопсий пациентов, страдавших инфекцией COVID-19. При помощи макро- и микроскопического исследований продемонстрированы особенности патологических процессов в различных органах. Полученные данные в сочетании со сведениями из литературы позволяют сделать выводы о закономерностях поражения внутренних органов и систем организма, а также высказать предположения об отдельных звеньях патогенеза COVID-19. Обсуждается танатогенез при данном заболевании и основные причины смерти, к которым относятся: острая сердечно-легочная недостаточность, острая почечная недостаточность, тромбоэмболия легочной артерии, шок с полиорганной недостаточностью и сепсис. Подчеркивается чрезвычайная важность проведения аутопсий, которые несут неоценимую информацию о морфологическом субстрате данной инфекции, тесно связанном с возможными клиническими проявлениями.
Список литературы

1. World Health Organization Coronavirus disease 2019 (COVID-19) situation report—51. World Health Organization, 2020. https://www.who.int/docs/default-source/coronaviruse/situationreports/20200311-sitrep-51-covid-19.pdf?sfvrsnј1ba62e57_10

2. Chan J. F., Yuan S., Kok K. H., To K. K., Chu H., Yang J., 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(10223):514–523. https://doi.org/10.1016/S0140-6736(20)30154-9

3. Ghinai I., McPherson T. D., Hunter J. C., Kirking H. L., Christiansen D., et al. Illinois COVID-19 Investigation Team. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;S0140-6736(20)):30607–3. https://doi.org/10.1016/S0140-6736(20)30607-3

4. Zhao D., Yao F., Wang L., Zheng L., Gao Y., Ye J., et al. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clin. Infect. Dis. 2020;ciaa247. https://doi.org/10.1093/cid/ciaa247

5. Xiong Y., Sun D., Liu Y., Fan Y., Zhao L., Li X., Zhu W. Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes. Investig. Radiol. 2020. https://doi.org/10.1097/RLI.0000000000000674

6. Park W. B., Kwon N. J., Choi S.J., Kang C. K., Choe P. G., Kim J. Y., et al. Virus isolation from the first patient with SARS-CoV-2 in Korea. J. Korean Med. Sci. 2020;35(7):e84. https://doi.org/10.3346/jkms.2020.35.e84

7. Walls A. C., Park Y. J., Tortorici M. A., Wall A., McGuire A. T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;180:1–12. https://doi.org/10.1016/j.cell.2020.02.058

8. 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;181:1–10. https://doi.org/10.1016/j.cell.2020.02.052

9. Finlay B. B., See R. H., Brunham R. C. Rapid response research to emerging infectious diseases: lessons from SARS. Nat. Rev. Microbiol. 2004;2(7):602–607.

10. Wrapp D., Wang N., Corbett K. S., Goldsmith J. A., Hsieh C. L., Abiona O. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. https://doi.org/10.1126/science.abb2507

11. Coutard B., Valle C., de Lamballerie X., Canard B., Seidah N. G., Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antivir. Res. 2020;176:104742. https://doi.org/10.1016/j.antiviral.2020.104742

12. Perrella A., Trama U., Bernardi F. F., Russo G., Monastra L., Fragranza F., et al. Editorial — COVID-19, more than a viral pneumonia. European Review for Medical and Pharmacological Sciences. 2020;24:5183–5185.

13. Aguiar D., Lobrinus J. A., Schibler M., Fracasso T., Lardi1 C. Inside the lungs of COVID-19 disease. International Journal of Legal Medicine. 2020;(134):1271–1274. https://doi.org/10.1007/s00414-020-02318-9

14. Pomara C., Volti G. L., Cappello F. COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy! J. Clin. Med. 2020;9:1259. https://doi.org/10.3390/jcm9051259

15. Cамсонова М. В., Михалева Л. М., Черняев А. Л., Мишнев О. Д., Крупнов Н. М. Патологическая анатомия легких при COVID-19: Атлас; под ред. О. В. Зайратьянца. М.—Рязань: Издательство ГУП РО «Рязанская областная типография», 2020.

16. Katzenstein F.-L. Diagnostic atlas of non-neoplastic lung disease. A practical guide for surgical pathologist. New York, NY: Demos Medical Publishing, 2016.

17. Costabel U., du Bois R. M., Egan J. J. (eds.) Diffuse Parenchymal Lung Disease. Prog. Respir. Res. 2007;36:1–10. https://doi.org/10.1159/000102577

18. Wallace A.H., Simpson J., Hirani N. Spencer’s pathology of the lung. Vol. 1. Ed. Ph. Hasleton, D.B. Frieder. Acute lung injury. Cambridge: Cambridge University Press. 2013;1:342–365.

19. Jain A. COVID-19 and lung pathology. Indian J. Pathol. Microbiol. 2020;63:171–172.

20. Huang C., Wang Y., Li X., Ren L, Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5

21. Guzik T. J., et al. COVID-19 and the cardiovascular system implications for risk assessment, diagnosis, and treatment options. Cardiovascular Research. 2020. https://doi.org/10.1093/cvr/cvaa106

22. Xiong T. Y., Redwood S., Prendergast B., Chen M. Coronaviruses and the cardiovascular system: acute and longterm implications. European Heart Journal. 2020;0:1–3. https://doi.org/10.1093/eurheartj/ehaa231

23. Kochi A. N., Tagliari A. P., Forleo G. B., Fassini G. M., Tondo C. Cardiac and arrhythmic complications in patients with COVID‐19. J Cardiovasc Electrophysiol. 2020;31:1003–1008. https://doi.org/10.1111/jce.14479

24. Manish Bansal. Cardiovascular disease and COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14:247–250. https://doi.org/10.1016/j.dsx.2020.03.013

25. Mahmud E., Dauerman H. L., Welt F. G., Messenger J. C., Rao S. V., Grines C., et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. Journal of the American College of Cardiology. 2020. https://doi.org/10.1016/j.jacc.2020.04.039

26. Zheng Y.-Y., Yi M.-T., Zhang J. -Y., Xie X. COVID-19 and the cardiovascular system. Nature reviews. 2020;17:259–260. 27. Thygesen K., Alpert J. S., Jaffe A.S., Chaitman B. R., Bax J. J., Morrow D. A., et al. ESC Scientific Document Group. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40(3):237–269. https://doi.org/10.1093/eurheartj/ehy462

27. Bikdeli B., Madhavan M.V., Jimenez D., Chuich T., Dreyfus I., Driggin E., et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. Journal of the American College of Cardiology. 2020. https://doi.org/10.1016/j.jacc.2020.04.031

28. Long B., Brady W. J., Koyfman A., et al. Cardiovascular complications in COVID-19. American Journal of Emergency Medicine. https://doi.org/10.1016/j.ajem.2020.04.048

29. Craver R., Huber S., Sandomirsky M., McKenna D., Schieffelin J., Finger L. Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c). =Fetal Pediatr. Pathol. 2020:1–6. https://doi.org/10.1080/15513815.2020.1761491. [Epub ahead of print].

30. Sala S., Peretto G., Gramegna M., Palmisano A., Villatore A., Vignale D., et al. Acute Myocarditis Presenting as a Reverse Tako-Tsubo Syndrome in a Patient With SARS-CoV-2 Respiratory Infection. Eur. Heart J. 2020;41(19):1861–1862. https://doi.org/10.1093/eurheartj/ehaa286

31. Liu P. P., Blet A., Smyth D., Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020 Apr 15. https://doi.org/10.1161/CIRCULATIONAHA.120.047549. [Epub ahead of print].

32. Arentz M., Yim E., Klaff L., et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020 [Epub ahead of print]. 34. Chen T., Wu D., Chen H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. Mar 26 2020;368:m1091.

33. Das G., Mukherjee N., Ghosh S. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020;11(9):1206–1209. https://doi.org/10.1021/acschemneuro.0c00201

34. Naicker S., Yang C.-W., Hwang S.-J., Liu B.-C., Chen J.-H., Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int. 2020;97:824–828. https://doi.org/10.1016/j.kint.2020.03.001

35. 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;8:475–481. https://doi.org/10.1016/S2213-2600(20)30079-5

36. Aragão D.S., Cunha T.S., Arita D.Y., Andrade M.C.C., Fernandes A.B., Watanabe I.K.M., et al. Purification and characterization of angiotensin converting enzyme 2 (ACE2) from murine model of mesangial cell in culture. Int. J. Biol. Macromol. 2011;49:79–84. https://doi.org/10.1016/j.ijbiomac.2011.03.018

37. Hamming I., Timens W., Bulthuis M. L. C., Lely A. T., 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;203:631–637. https://doi.org/10.1002/path.1570

38. Li N., Zimpelmann J., Cheng K., Wilkins J.A., Burns K. D. The role of angiotensin converting enzyme 2 in the generation of angiotensin 1_7 by rat proximal tubules. Am. J. Physiol. Renal. Physiol. 2005;288:F353–F362. https://doi.org/10.1152/ajprenal.00144.2004

39. Ye M., Wysocki J., William J., Soler M. J., Cokic I., Batlle D. Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes. J. Am. Soc. Nephrol. 2006;17:3067–3075. https://doi.org/10.1681/ASN.2006050423

40. Liu H., Jiang Y., Li M., Yu X., Sui D., Fu L. Ginsenoside Rg3 attenuates angiotensin II-mediated renal injury in rats and mice by upregulating angiotensin-converting enzyme 2 in the renal tissue. Evid. Based Complement. Alternat Med. 2019;6741057. https://doi.org/10.1155/2019/6741057

41. Mizuiri S., Ohashi Y. ACE and ACE2 in kidney disease. World J. Nephrol. 2015;4:74–82. https://doi.org/10.5527/wjn.v4.i1.74

42. Sharma N., Malek V., Mulay S. R., Gaikwad A. B. Angiotensin II type 2 receptor and angiotensin-converting enzyme 2 mediate ischemic renal injury in diabetic and non-diabetic rats. Life Sci. 2019;235:116796. https://doi.org/10.1016/j.lfs.2019.116796

43. Oudit G. Y., Herzenberg A. M., Kassiri Z., Wong D., Reich H., Khokha R., et al. Loss of angiotensin-conver ting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am. J. Pathol. 2006;168:1808–1820. https://doi.org/10.2353/ajpath.2006.051091

44. Jessup J. A., Gallagher P. E., Averill D. B., Brosnihan K. B., Tallant E. A., Chappell M. C., Ferrario C. M. Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. Am. J. Physiol. Heart Circ. Physiol. 2006;291:H2166–H2172. https://doi.org/10.1152/ajpheart.00061.2006

45. van de Veerdonk F., Netea M. G., van Deuren M., van der Meer J. W., de Mast Q., Bruggemann R. J., van der Hoeven H. Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach. Preprints. 2020:2020040023. https://doi.org/10.20944/preprints202004.0023.v1

46. Cheng H., Wang, Y., & Wang, G. Q. Organ‐protective Effect of Angiotensin‐converting Enzyme 2 and its Effect on the Prognosis of COVID‐19. Journal of Medical Virology. 2020. PMID 32221983. https://doi.org/10.1002/jmv.25785

47. Diao B., Feng Z., Wang C., Wang H., Liu L., Wang C., et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Preprint. medRxiv: 2020.03.04:20031120. https://doi.org/10.1101/2020.03.04.20031120

48. Perico L., Benigni A., Remuzzi G. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade. Nephron. In press. https://doi.org/10.1159/000507305

49. Su H., Yang M., Wan C., Yi L. X., Tang F., Zhu H. Y., et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. In press. https://doi.org/10.1016/j.kint.2020.04.003

50. D’Agati V. D., Kaskel F. J., Falk R. J. Focal segmental glomerulosclerosis. N. Engl. J. Med. 2011;365:2398–2411.

51. Shkreli M., Sarin K. Y., Pech M. F., et al. Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling. Nat Med. 2011;18:111–119.

52. Larsen C. P., Bourne T. D., Wilson J. D., et al. Collapsing Glomerulopathy in a Patient With Coronavirus Disease 2019 (COVID-19). Kidney Int Rep. 2020. 55. Peleg Y., Kudose S., D’Agati V., et al. Acute Kidney Injury Due to Collapsing Glomerulopathy Following COVID-19 Infection. Kidney Int Rep. 2020.

53. Kissling S., Rotman S., Gerber C., et al. Collapsing glomerulopathy in a COVID-19 patient. Kidney Int. 2020.

54. Cheng Y., Luo R., Wang K., Zhang M., Wang Z., Dong L., et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:829–838. https://doi.org/10.1016/j.kint.2020. 03.005.

55. Nasr S. H., Kopp J. B. COVID-19-Associated Collapsing Glomerulopathy. Kidney Int. Rep. 2020;5:759–761. https://doi.org/10.1016/j.ekir.2020.04.030

56. Hirsch J. S., Ng J. H., Ross D. W., Sharma P., Shah H. H., Barnett R. L., et al. Northwell COVID-19 Research Consortium; Northwell Nephrology COVID-19 Research Consortium. Acute kidney injury in patients hospitalized with COVID-19, Kidney Int. 2020 May 16;S0085–2538(20):30532–30539. https://doi.org/10.1016/j.kint.2020.05.006 Online ahead of print. Kidney Int. 2020. PMID: 32416116

57. Post A., den Deurwaarder E. S. G., Bakker S. J. L., de Haas R. J., van Meurs M., Gansevoort R. T., Berger S. P. Kidney Infarction in Patients With COVID-19 American Journal of Kidney Diseases. 2020. https://doi.org/10.1053/j.ajkd.2020.05.004

58. Zhang C., Shi L., Wang F.-S. Liver injury in COVID-19: management and challenges. www.thelancet.com/gastrohep Vol 5 May 2020, Published Online March 4, 2020. https://doi.org/10.1016/S2468-1253(20)30057-1

59. Ye Z., Song B. COVID-19 related liver injury: call for international consensus. Clinical Gastroenterology and Hepatology. 2020. https://doi.org/10.1016/j.cgh.2020.05.013

60. Zheng K.I., Gao F., Wang X.-B., Sun Q.-F., Pan K.-H., Wang T.-Y., et al. Letter to the Editor: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism Clinical and Experimental. 2020. https://doi.org/10.1016/j.metabol.2020.154244

61. Jinyang Gu, Bing Han, Jian Wang, COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology. 2020;158:1518–1519. https://doi.org/10.1053/j.gastro.2020.02.054

62. Wang Y., Liu S., Liu H., Li W., Lin F., Jiang L., et al. SARSCoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. Journal of Hepatology. 2020. https://doi.org/10.1016/j.jhep.2020.05.002

63. Tian Y., Rong L., Nian W., He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Alimentary Pharmacology and Therapeutics. 2020;51(9):843–851. https://doi.org/10.1111/apt.15731

64. Xiao F., Tang M., Zheng X., Liu Y., Li X., & Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–1833.e3. https://doi.org/10.1053/j.gastro.2020.02.055

65. Bezzio C., Saibeni S., Variola A., Allocca M., Massari A., Gerardi V., et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: An IG-IBD study. Gut. 2020:1213–1217. https://doi.org/10.1136/gutjnl-2020-321411

66. Pal R., Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01276-8

67. 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 [Internet] [cited 2020 Apr 1].

68. Ding Y., He L., Zhang Q., Huang Z., Che X., Hou J., et al. Organ distribution of severe acute respiratory syndrome(SARS) associated coronavirus(SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004;203:622–630. https://doi.org/10.1002/path.1560

69. Yang J. K., Feng Y., Yuan M. Y., Yuan S. Y., Fu H. J., Wu B. Y., et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23:623–628. https://doi.org/10.1111/j.1464-5491.2006.01861

70. 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. https://doi.org/10.1007/s00592-009-0109-4.x

71. Jaeckel E., Manns M., Herrath M. Viruses and diabetes. Ann. N. Y. Acad. Sci. 2006;958:7–25. https://doi.org/10.1111/j.1749-6632.2002.tb02943.x

72. Wheatland R. Molecular mimicry of ACTH in SARS — implications for corticosteroid treatment and prophylaxis. Med. Hypotheses. 2004;63:855–862. https://doi.org/10.1016/j.mehy.2004.04.009

73. Xu J., Zhao S., Teng T., Abdalla A.E., Zhu W., Xie L., et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARSCoV. Viruses. 2020;12:244. https://doi.org/10.3390/v12020244

74. Isidori A. M., Arnaldi G., Boscaro M., Falorni A., Giordano C., Giordano R., et al. COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency. J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01266-w

75. Scaroni C., Armigliato M., Cannavò S. COVID-19 outbreak and steroids administration: are patients treated for Sars-Cov-2 at risk of adrenal insufficiency? J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01253-1

76. Porfidia A., Pola R., Porfidia A., et al. Venous thromboembolism in COVID-19 patients. J. Throm. Haemost. 2020. https://doi.org/10.1111//jth.14842

77. 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. https://doi.org/10.1016/j.humpath.2006.06.011.Р

78. 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. https://doi.org/10.1016/j.humpath.2006.06.011

79. Desaillud R., Hober D. Virus and thyroiditis: an update. Virol. J. 2009;6:5. https://doi.org/10.1186/1743-422X-6-5

80. Bellastella G., Maiorino M. I., Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands? Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01311-8

81. Liang Y., Wang M.-L., Chien C.-S., Yarmishyn A. A., Yang Y.-P., Lai W.-Y., et al. Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection. Front. Immunol. 2020;11:1022.

82. Lega S., Naviglio S., Volpi S., Tommasini A. Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19. Vaccines. 2020;8:224–254. https://doi.org/10.3390/vaccines8020224

83. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol. Immunol. 2020;17:533–5. https://doi.org/10.1038/s41423-020-0402-2

84. Zeng Q., Li Y., Huang G., Wu W., Dong S., Xu Y. Mortality of COVID-19 is associated with cellular immune function compared to immune function in Chinese Han population. Medrxiv. 2020. https://doi.org/10.1101/2020.03.08.20031229

85. Zheng J. SARS-CoV-2: An Emerging Coronavirus that Causes a Global Threat. Int. J. Biol. Sci. 2020;16:1678–1685. [CrossRef]

86. Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., et al. SARSCoV-2 infects T lymphocytes through its spike proteinmediated membrane fusion. Cell Mol. Immunol. 2020;1–3. https://doi.org/10.1038/s41423-020-0424-9

87. 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 inWuhan, China: A descriptive study. Lancet. 2020;395:507–513. [CrossRef]

88. Wang D., Hu B., Hu, C., Zhu F., Liu X., Zhang J., et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. [CrossRef]

89. Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., et al. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell. Mol. Immunol. 2020;1–3. [CrossRef]

90. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J. Eur. Acad. Dermatol. Venereol. 2020. http://dx.doi.org/10.1111/jdv.16387 [Epub ahead of print].

91. Sachdeva M., Gianottibc R., Shhaha M., Lucia B., Tosi D., Veraldic S., et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J. Dermatol. Sci. 2020). https://doi.org/10.1016/j. jdermsci.2020.04.011

92. Gianotti R. COVID 19 and the skin-heuristic review, Dermo Sprint. 2020. April 06. In press.

93. Manalo I. F., Smith M. K., Cheeley J., Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J. Am. Acad. Dermatol. 2020. http://dx.doi.org/10.1016/j.jaad.2020.04.018 [Epub ahead of print].

94. Magro C., Mulvey J., Berlin D., Nuovo G., Salvatore S., Harp J., et al. Complementary associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases, Transl. Res. 2020. In press.

95. Ayala E., Kagawa F. T., Wehner J. H., Tam J., Upadhyay D. Rhabdomyolysis associated with 2009 influenza A(H1N1). JAMA. 2009;302:1863–1864. https://doi.org/10.1001/jama.2009.1582

96. Jin Min & Tong Qiaoxia. Rhabdomyolysis as Potential Late Complication Associated with COVID-19. Emerging infectious diseases. 2020. https://doi.org/10.3201/eid2607.200445

97. Lahiri D., Ardila A. COVID-19 Pandemic: A Neurological Perspective. Cureus. 2020;12(4):e7889. https://doi.org/10.7759/cureus.7889

98. Xu J., Qi L., Chi X. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 2006;74:410– 416. [PMC free article] [PubMed] [Google Scholar]

99. Ding Y., He L., Zhang Q. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004;203:622–630. [PMC free article] [PubMed] [Google Scholar]

100. Fan C., Li K., Ding Y., Lu W., Wang JACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv. 2020.

101. Shen Q., Xiao X., Aierken A., Liao M., Hua J. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. medRxiv. 2020

102. Song C., Wang Y., Li W., Hu B., Chen G., Xia P., et al. https://doi.org/10.1101/2020.03.31.20042333

103. Li R., Yin T., Fang F., Li Q., Chen J., Wang Y., et al. Potential risks of SARS-CoV-2 infection on reproductive health. ReproductiveBioMedicine. 2020 (Onlinehttps:// doi.org/). https://doi.org/10.1016/j.rbmo.2020.04.018

104. di Mascio D., Khalil A., Saccone G., Nappi L., Scambia G., Berghella V., D’Antonio F. Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1–19) during pregnancy: a systematic review and meta-analysis. [Published online ahead of print, 2020 Mar 25]. American Journal of Obstetrics and Gynecology. MFM. 2020;100107. https://doi.org/10.1016/j.ajogmf.2020.100107

105. Schwartz D. A., Graham A. L. Potential maternal and infant outcomes from Coronavirus 2019-nCoV (SARSCoV-2) infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses. 2020;12(2):194. https://doi.org/10.3390/v12020194

106. Ferrazzi E. M., Frigerio L., Cetin I., Vergani P., Spinillo A., Prefumo F., et al. COVID-19 Obstetrics Task Force, Lombardy, Italy: executive management summary and short report of outcome. International Journal of Gynecology and Obstetrics. 2020. [Published online ahead of print, 2020 Apr 8]. https://doi.org/10.1002/ijgo.13162

107. Conaldi P. G., et al. Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells. J. Virol. 1997;71(12):9180–9187.

108. Nowakowski T. J., et al. Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells. Cell Stem. Cell. 2016;18(5):591–596.

109. Jayawardena N., et al. Virus-Receptor Interactions: Structural Insights for Oncolytic Virus Development. Oncolytic Virother. 2019;8:39–56.

110. CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children — United States, February 12 — April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:422.

111. Dong Y., Mo X., Hu Y., et al. Epidemiology of COVID-19 among Children in China. Pediatrics 2020; 145.

112. Zimmermann P., Curtis N. Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children. Pediatr Infect Dis J. 2020;39:355.

113. McCrindle B. W., Rowley A. H., Newburger J. W., et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–e999. https://doi.org/10.1161/CIR.0000000000000484

Russian Journal of Forensic Medicine. 2020; 6: 8-30

PATHOLOGICAL ANATOMY OF INFECTION CAUSED BY SARS-COV-2

Kogan E. A., Berezovsky Yu. S., Protsenko D. D., Bagdasaryan T. R., Gretsov E. M., Demura S. A., Demyashkin G. A., Kalinin D. V., Kukleva A. D., Kurilina E. V., Nekrasova T. P., Paramonova N. B., Ponomarev A. B., Radenska-Lopovok S. G., Semyonova L. A., Tertychny A. S.

https://doi.org/10.19048/2411-8729-2020-6-2-8-30

Abstract

Autopsy data from 80 patients who died of the COVID-19 infection were analysed. Using macro- and microscopic studies, specific features of pathological processes in various organs were identified. The obtained experimental data, along with information from literature sources, allowed conclusions to be drawn about the mechanisms of damaging internal organs and body systems, as well as assumptions to be made about individual links in the pathogenesis of COVID-19. The thanatogenesis of the disease and the main causes of death are discussed, including acute cardiopulmonary failure, acute renal failure, pulmonary thromboembolism, shock involving multiple organ failure and sepsis. The critical importance of autopsy is emphasized, which provides valuable information on the morphological substrate for this infection closely associated with possible clinical manifestations.
References

1. World Health Organization Coronavirus disease 2019 (COVID-19) situation report—51. World Health Organization, 2020. https://www.who.int/docs/default-source/coronaviruse/situationreports/20200311-sitrep-51-covid-19.pdf?sfvrsnј1ba62e57_10

2. Chan J. F., Yuan S., Kok K. H., To K. K., Chu H., Yang J., 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(10223):514–523. https://doi.org/10.1016/S0140-6736(20)30154-9

3. Ghinai I., McPherson T. D., Hunter J. C., Kirking H. L., Christiansen D., et al. Illinois COVID-19 Investigation Team. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;S0140-6736(20)):30607–3. https://doi.org/10.1016/S0140-6736(20)30607-3

4. Zhao D., Yao F., Wang L., Zheng L., Gao Y., Ye J., et al. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clin. Infect. Dis. 2020;ciaa247. https://doi.org/10.1093/cid/ciaa247

5. Xiong Y., Sun D., Liu Y., Fan Y., Zhao L., Li X., Zhu W. Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes. Investig. Radiol. 2020. https://doi.org/10.1097/RLI.0000000000000674

6. Park W. B., Kwon N. J., Choi S.J., Kang C. K., Choe P. G., Kim J. Y., et al. Virus isolation from the first patient with SARS-CoV-2 in Korea. J. Korean Med. Sci. 2020;35(7):e84. https://doi.org/10.3346/jkms.2020.35.e84

7. Walls A. C., Park Y. J., Tortorici M. A., Wall A., McGuire A. T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;180:1–12. https://doi.org/10.1016/j.cell.2020.02.058

8. 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;181:1–10. https://doi.org/10.1016/j.cell.2020.02.052

9. Finlay B. B., See R. H., Brunham R. C. Rapid response research to emerging infectious diseases: lessons from SARS. Nat. Rev. Microbiol. 2004;2(7):602–607.

10. Wrapp D., Wang N., Corbett K. S., Goldsmith J. A., Hsieh C. L., Abiona O. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. https://doi.org/10.1126/science.abb2507

11. Coutard B., Valle C., de Lamballerie X., Canard B., Seidah N. G., Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antivir. Res. 2020;176:104742. https://doi.org/10.1016/j.antiviral.2020.104742

12. Perrella A., Trama U., Bernardi F. F., Russo G., Monastra L., Fragranza F., et al. Editorial — COVID-19, more than a viral pneumonia. European Review for Medical and Pharmacological Sciences. 2020;24:5183–5185.

13. Aguiar D., Lobrinus J. A., Schibler M., Fracasso T., Lardi1 C. Inside the lungs of COVID-19 disease. International Journal of Legal Medicine. 2020;(134):1271–1274. https://doi.org/10.1007/s00414-020-02318-9

14. Pomara C., Volti G. L., Cappello F. COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy! J. Clin. Med. 2020;9:1259. https://doi.org/10.3390/jcm9051259

15. Camsonova M. V., Mikhaleva L. M., Chernyaev A. L., Mishnev O. D., Krupnov N. M. Patologicheskaya anatomiya legkikh pri COVID-19: Atlas; pod red. O. V. Zairat'yantsa. M.—Ryazan': Izdatel'stvo GUP RO «Ryazanskaya oblastnaya tipografiya», 2020.

16. Katzenstein F.-L. Diagnostic atlas of non-neoplastic lung disease. A practical guide for surgical pathologist. New York, NY: Demos Medical Publishing, 2016.

17. Costabel U., du Bois R. M., Egan J. J. (eds.) Diffuse Parenchymal Lung Disease. Prog. Respir. Res. 2007;36:1–10. https://doi.org/10.1159/000102577

18. Wallace A.H., Simpson J., Hirani N. Spencer’s pathology of the lung. Vol. 1. Ed. Ph. Hasleton, D.B. Frieder. Acute lung injury. Cambridge: Cambridge University Press. 2013;1:342–365.

19. Jain A. COVID-19 and lung pathology. Indian J. Pathol. Microbiol. 2020;63:171–172.

20. Huang C., Wang Y., Li X., Ren L, Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5

21. Guzik T. J., et al. COVID-19 and the cardiovascular system implications for risk assessment, diagnosis, and treatment options. Cardiovascular Research. 2020. https://doi.org/10.1093/cvr/cvaa106

22. Xiong T. Y., Redwood S., Prendergast B., Chen M. Coronaviruses and the cardiovascular system: acute and longterm implications. European Heart Journal. 2020;0:1–3. https://doi.org/10.1093/eurheartj/ehaa231

23. Kochi A. N., Tagliari A. P., Forleo G. B., Fassini G. M., Tondo C. Cardiac and arrhythmic complications in patients with COVID‐19. J Cardiovasc Electrophysiol. 2020;31:1003–1008. https://doi.org/10.1111/jce.14479

24. Manish Bansal. Cardiovascular disease and COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14:247–250. https://doi.org/10.1016/j.dsx.2020.03.013

25. Mahmud E., Dauerman H. L., Welt F. G., Messenger J. C., Rao S. V., Grines C., et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. Journal of the American College of Cardiology. 2020. https://doi.org/10.1016/j.jacc.2020.04.039

26. Zheng Y.-Y., Yi M.-T., Zhang J. -Y., Xie X. COVID-19 and the cardiovascular system. Nature reviews. 2020;17:259–260. 27. Thygesen K., Alpert J. S., Jaffe A.S., Chaitman B. R., Bax J. J., Morrow D. A., et al. ESC Scientific Document Group. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40(3):237–269. https://doi.org/10.1093/eurheartj/ehy462

27. Bikdeli B., Madhavan M.V., Jimenez D., Chuich T., Dreyfus I., Driggin E., et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. Journal of the American College of Cardiology. 2020. https://doi.org/10.1016/j.jacc.2020.04.031

28. Long B., Brady W. J., Koyfman A., et al. Cardiovascular complications in COVID-19. American Journal of Emergency Medicine. https://doi.org/10.1016/j.ajem.2020.04.048

29. Craver R., Huber S., Sandomirsky M., McKenna D., Schieffelin J., Finger L. Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c). =Fetal Pediatr. Pathol. 2020:1–6. https://doi.org/10.1080/15513815.2020.1761491. [Epub ahead of print].

30. Sala S., Peretto G., Gramegna M., Palmisano A., Villatore A., Vignale D., et al. Acute Myocarditis Presenting as a Reverse Tako-Tsubo Syndrome in a Patient With SARS-CoV-2 Respiratory Infection. Eur. Heart J. 2020;41(19):1861–1862. https://doi.org/10.1093/eurheartj/ehaa286

31. Liu P. P., Blet A., Smyth D., Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020 Apr 15. https://doi.org/10.1161/CIRCULATIONAHA.120.047549. [Epub ahead of print].

32. Arentz M., Yim E., Klaff L., et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020 [Epub ahead of print]. 34. Chen T., Wu D., Chen H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. Mar 26 2020;368:m1091.

33. Das G., Mukherjee N., Ghosh S. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020;11(9):1206–1209. https://doi.org/10.1021/acschemneuro.0c00201

34. Naicker S., Yang C.-W., Hwang S.-J., Liu B.-C., Chen J.-H., Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int. 2020;97:824–828. https://doi.org/10.1016/j.kint.2020.03.001

35. 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;8:475–481. https://doi.org/10.1016/S2213-2600(20)30079-5

36. Aragão D.S., Cunha T.S., Arita D.Y., Andrade M.C.C., Fernandes A.B., Watanabe I.K.M., et al. Purification and characterization of angiotensin converting enzyme 2 (ACE2) from murine model of mesangial cell in culture. Int. J. Biol. Macromol. 2011;49:79–84. https://doi.org/10.1016/j.ijbiomac.2011.03.018

37. Hamming I., Timens W., Bulthuis M. L. C., Lely A. T., 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;203:631–637. https://doi.org/10.1002/path.1570

38. Li N., Zimpelmann J., Cheng K., Wilkins J.A., Burns K. D. The role of angiotensin converting enzyme 2 in the generation of angiotensin 1_7 by rat proximal tubules. Am. J. Physiol. Renal. Physiol. 2005;288:F353–F362. https://doi.org/10.1152/ajprenal.00144.2004

39. Ye M., Wysocki J., William J., Soler M. J., Cokic I., Batlle D. Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes. J. Am. Soc. Nephrol. 2006;17:3067–3075. https://doi.org/10.1681/ASN.2006050423

40. Liu H., Jiang Y., Li M., Yu X., Sui D., Fu L. Ginsenoside Rg3 attenuates angiotensin II-mediated renal injury in rats and mice by upregulating angiotensin-converting enzyme 2 in the renal tissue. Evid. Based Complement. Alternat Med. 2019;6741057. https://doi.org/10.1155/2019/6741057

41. Mizuiri S., Ohashi Y. ACE and ACE2 in kidney disease. World J. Nephrol. 2015;4:74–82. https://doi.org/10.5527/wjn.v4.i1.74

42. Sharma N., Malek V., Mulay S. R., Gaikwad A. B. Angiotensin II type 2 receptor and angiotensin-converting enzyme 2 mediate ischemic renal injury in diabetic and non-diabetic rats. Life Sci. 2019;235:116796. https://doi.org/10.1016/j.lfs.2019.116796

43. Oudit G. Y., Herzenberg A. M., Kassiri Z., Wong D., Reich H., Khokha R., et al. Loss of angiotensin-conver ting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am. J. Pathol. 2006;168:1808–1820. https://doi.org/10.2353/ajpath.2006.051091

44. Jessup J. A., Gallagher P. E., Averill D. B., Brosnihan K. B., Tallant E. A., Chappell M. C., Ferrario C. M. Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. Am. J. Physiol. Heart Circ. Physiol. 2006;291:H2166–H2172. https://doi.org/10.1152/ajpheart.00061.2006

45. van de Veerdonk F., Netea M. G., van Deuren M., van der Meer J. W., de Mast Q., Bruggemann R. J., van der Hoeven H. Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach. Preprints. 2020:2020040023. https://doi.org/10.20944/preprints202004.0023.v1

46. Cheng H., Wang, Y., & Wang, G. Q. Organ‐protective Effect of Angiotensin‐converting Enzyme 2 and its Effect on the Prognosis of COVID‐19. Journal of Medical Virology. 2020. PMID 32221983. https://doi.org/10.1002/jmv.25785

47. Diao B., Feng Z., Wang C., Wang H., Liu L., Wang C., et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Preprint. medRxiv: 2020.03.04:20031120. https://doi.org/10.1101/2020.03.04.20031120

48. Perico L., Benigni A., Remuzzi G. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade. Nephron. In press. https://doi.org/10.1159/000507305

49. Su H., Yang M., Wan C., Yi L. X., Tang F., Zhu H. Y., et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. In press. https://doi.org/10.1016/j.kint.2020.04.003

50. D’Agati V. D., Kaskel F. J., Falk R. J. Focal segmental glomerulosclerosis. N. Engl. J. Med. 2011;365:2398–2411.

51. Shkreli M., Sarin K. Y., Pech M. F., et al. Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling. Nat Med. 2011;18:111–119.

52. Larsen C. P., Bourne T. D., Wilson J. D., et al. Collapsing Glomerulopathy in a Patient With Coronavirus Disease 2019 (COVID-19). Kidney Int Rep. 2020. 55. Peleg Y., Kudose S., D’Agati V., et al. Acute Kidney Injury Due to Collapsing Glomerulopathy Following COVID-19 Infection. Kidney Int Rep. 2020.

53. Kissling S., Rotman S., Gerber C., et al. Collapsing glomerulopathy in a COVID-19 patient. Kidney Int. 2020.

54. Cheng Y., Luo R., Wang K., Zhang M., Wang Z., Dong L., et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:829–838. https://doi.org/10.1016/j.kint.2020. 03.005.

55. Nasr S. H., Kopp J. B. COVID-19-Associated Collapsing Glomerulopathy. Kidney Int. Rep. 2020;5:759–761. https://doi.org/10.1016/j.ekir.2020.04.030

56. Hirsch J. S., Ng J. H., Ross D. W., Sharma P., Shah H. H., Barnett R. L., et al. Northwell COVID-19 Research Consortium; Northwell Nephrology COVID-19 Research Consortium. Acute kidney injury in patients hospitalized with COVID-19, Kidney Int. 2020 May 16;S0085–2538(20):30532–30539. https://doi.org/10.1016/j.kint.2020.05.006 Online ahead of print. Kidney Int. 2020. PMID: 32416116

57. Post A., den Deurwaarder E. S. G., Bakker S. J. L., de Haas R. J., van Meurs M., Gansevoort R. T., Berger S. P. Kidney Infarction in Patients With COVID-19 American Journal of Kidney Diseases. 2020. https://doi.org/10.1053/j.ajkd.2020.05.004

58. Zhang C., Shi L., Wang F.-S. Liver injury in COVID-19: management and challenges. www.thelancet.com/gastrohep Vol 5 May 2020, Published Online March 4, 2020. https://doi.org/10.1016/S2468-1253(20)30057-1

59. Ye Z., Song B. COVID-19 related liver injury: call for international consensus. Clinical Gastroenterology and Hepatology. 2020. https://doi.org/10.1016/j.cgh.2020.05.013

60. Zheng K.I., Gao F., Wang X.-B., Sun Q.-F., Pan K.-H., Wang T.-Y., et al. Letter to the Editor: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism Clinical and Experimental. 2020. https://doi.org/10.1016/j.metabol.2020.154244

61. Jinyang Gu, Bing Han, Jian Wang, COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology. 2020;158:1518–1519. https://doi.org/10.1053/j.gastro.2020.02.054

62. Wang Y., Liu S., Liu H., Li W., Lin F., Jiang L., et al. SARSCoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. Journal of Hepatology. 2020. https://doi.org/10.1016/j.jhep.2020.05.002

63. Tian Y., Rong L., Nian W., He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Alimentary Pharmacology and Therapeutics. 2020;51(9):843–851. https://doi.org/10.1111/apt.15731

64. Xiao F., Tang M., Zheng X., Liu Y., Li X., & Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–1833.e3. https://doi.org/10.1053/j.gastro.2020.02.055

65. Bezzio C., Saibeni S., Variola A., Allocca M., Massari A., Gerardi V., et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: An IG-IBD study. Gut. 2020:1213–1217. https://doi.org/10.1136/gutjnl-2020-321411

66. Pal R., Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01276-8

67. 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 [Internet] [cited 2020 Apr 1].

68. Ding Y., He L., Zhang Q., Huang Z., Che X., Hou J., et al. Organ distribution of severe acute respiratory syndrome(SARS) associated coronavirus(SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004;203:622–630. https://doi.org/10.1002/path.1560

69. Yang J. K., Feng Y., Yuan M. Y., Yuan S. Y., Fu H. J., Wu B. Y., et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23:623–628. https://doi.org/10.1111/j.1464-5491.2006.01861

70. 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. https://doi.org/10.1007/s00592-009-0109-4.x

71. Jaeckel E., Manns M., Herrath M. Viruses and diabetes. Ann. N. Y. Acad. Sci. 2006;958:7–25. https://doi.org/10.1111/j.1749-6632.2002.tb02943.x

72. Wheatland R. Molecular mimicry of ACTH in SARS — implications for corticosteroid treatment and prophylaxis. Med. Hypotheses. 2004;63:855–862. https://doi.org/10.1016/j.mehy.2004.04.009

73. Xu J., Zhao S., Teng T., Abdalla A.E., Zhu W., Xie L., et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARSCoV. Viruses. 2020;12:244. https://doi.org/10.3390/v12020244

74. Isidori A. M., Arnaldi G., Boscaro M., Falorni A., Giordano C., Giordano R., et al. COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency. J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01266-w

75. Scaroni C., Armigliato M., Cannavò S. COVID-19 outbreak and steroids administration: are patients treated for Sars-Cov-2 at risk of adrenal insufficiency? J. Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01253-1

76. Porfidia A., Pola R., Porfidia A., et al. Venous thromboembolism in COVID-19 patients. J. Throm. Haemost. 2020. https://doi.org/10.1111//jth.14842

77. 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. https://doi.org/10.1016/j.humpath.2006.06.011.R

78. 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. https://doi.org/10.1016/j.humpath.2006.06.011

79. Desaillud R., Hober D. Virus and thyroiditis: an update. Virol. J. 2009;6:5. https://doi.org/10.1186/1743-422X-6-5

80. Bellastella G., Maiorino M. I., Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands? Endocrinol. Invest. 2020. https://doi.org/10.1007/s40618-020-01311-8

81. Liang Y., Wang M.-L., Chien C.-S., Yarmishyn A. A., Yang Y.-P., Lai W.-Y., et al. Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection. Front. Immunol. 2020;11:1022.

82. Lega S., Naviglio S., Volpi S., Tommasini A. Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19. Vaccines. 2020;8:224–254. https://doi.org/10.3390/vaccines8020224

83. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol. Immunol. 2020;17:533–5. https://doi.org/10.1038/s41423-020-0402-2

84. Zeng Q., Li Y., Huang G., Wu W., Dong S., Xu Y. Mortality of COVID-19 is associated with cellular immune function compared to immune function in Chinese Han population. Medrxiv. 2020. https://doi.org/10.1101/2020.03.08.20031229

85. Zheng J. SARS-CoV-2: An Emerging Coronavirus that Causes a Global Threat. Int. J. Biol. Sci. 2020;16:1678–1685. [CrossRef]

86. Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., et al. SARSCoV-2 infects T lymphocytes through its spike proteinmediated membrane fusion. Cell Mol. Immunol. 2020;1–3. https://doi.org/10.1038/s41423-020-0424-9

87. 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 inWuhan, China: A descriptive study. Lancet. 2020;395:507–513. [CrossRef]

88. Wang D., Hu B., Hu, C., Zhu F., Liu X., Zhang J., et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. [CrossRef]

89. Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z., et al. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell. Mol. Immunol. 2020;1–3. [CrossRef]

90. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J. Eur. Acad. Dermatol. Venereol. 2020. http://dx.doi.org/10.1111/jdv.16387 [Epub ahead of print].

91. Sachdeva M., Gianottibc R., Shhaha M., Lucia B., Tosi D., Veraldic S., et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J. Dermatol. Sci. 2020). https://doi.org/10.1016/j. jdermsci.2020.04.011

92. Gianotti R. COVID 19 and the skin-heuristic review, Dermo Sprint. 2020. April 06. In press.

93. Manalo I. F., Smith M. K., Cheeley J., Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J. Am. Acad. Dermatol. 2020. http://dx.doi.org/10.1016/j.jaad.2020.04.018 [Epub ahead of print].

94. Magro C., Mulvey J., Berlin D., Nuovo G., Salvatore S., Harp J., et al. Complementary associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases, Transl. Res. 2020. In press.

95. Ayala E., Kagawa F. T., Wehner J. H., Tam J., Upadhyay D. Rhabdomyolysis associated with 2009 influenza A(H1N1). JAMA. 2009;302:1863–1864. https://doi.org/10.1001/jama.2009.1582

96. Jin Min & Tong Qiaoxia. Rhabdomyolysis as Potential Late Complication Associated with COVID-19. Emerging infectious diseases. 2020. https://doi.org/10.3201/eid2607.200445

97. Lahiri D., Ardila A. COVID-19 Pandemic: A Neurological Perspective. Cureus. 2020;12(4):e7889. https://doi.org/10.7759/cureus.7889

98. Xu J., Qi L., Chi X. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 2006;74:410– 416. [PMC free article] [PubMed] [Google Scholar]

99. Ding Y., He L., Zhang Q. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004;203:622–630. [PMC free article] [PubMed] [Google Scholar]

100. Fan C., Li K., Ding Y., Lu W., Wang JACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv. 2020.

101. Shen Q., Xiao X., Aierken A., Liao M., Hua J. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. medRxiv. 2020

102. Song C., Wang Y., Li W., Hu B., Chen G., Xia P., et al. https://doi.org/10.1101/2020.03.31.20042333

103. Li R., Yin T., Fang F., Li Q., Chen J., Wang Y., et al. Potential risks of SARS-CoV-2 infection on reproductive health. ReproductiveBioMedicine. 2020 (Onlinehttps:// doi.org/). https://doi.org/10.1016/j.rbmo.2020.04.018

104. di Mascio D., Khalil A., Saccone G., Nappi L., Scambia G., Berghella V., D’Antonio F. Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1–19) during pregnancy: a systematic review and meta-analysis. [Published online ahead of print, 2020 Mar 25]. American Journal of Obstetrics and Gynecology. MFM. 2020;100107. https://doi.org/10.1016/j.ajogmf.2020.100107

105. Schwartz D. A., Graham A. L. Potential maternal and infant outcomes from Coronavirus 2019-nCoV (SARSCoV-2) infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses. 2020;12(2):194. https://doi.org/10.3390/v12020194

106. Ferrazzi E. M., Frigerio L., Cetin I., Vergani P., Spinillo A., Prefumo F., et al. COVID-19 Obstetrics Task Force, Lombardy, Italy: executive management summary and short report of outcome. International Journal of Gynecology and Obstetrics. 2020. [Published online ahead of print, 2020 Apr 8]. https://doi.org/10.1002/ijgo.13162

107. Conaldi P. G., et al. Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells. J. Virol. 1997;71(12):9180–9187.

108. Nowakowski T. J., et al. Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells. Cell Stem. Cell. 2016;18(5):591–596.

109. Jayawardena N., et al. Virus-Receptor Interactions: Structural Insights for Oncolytic Virus Development. Oncolytic Virother. 2019;8:39–56.

110. CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children — United States, February 12 — April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:422.

111. Dong Y., Mo X., Hu Y., et al. Epidemiology of COVID-19 among Children in China. Pediatrics 2020; 145.

112. Zimmermann P., Curtis N. Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children. Pediatr Infect Dis J. 2020;39:355.

113. McCrindle B. W., Rowley A. H., Newburger J. W., et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–e999. https://doi.org/10.1161/CIR.0000000000000484