COVID-19 postmortem ve otopsi bulguları

COVİD 19 pandemisinde ilk olgunun izlendiği Aralık 2019’dan sonra geçen 15 ay içinde hastalığın tedavisinin bulunması için fizyopatolojisinin anlaşılması büyük önem taşımıştır. Postmortem inceleme ve otopsi bulguları ile hastalığın sadece bir pulmoner epitel hastalığı olmadığı anlaşılmıştır. Otopsi incelemeleri ile özellikle kötü klinik gidişli hastalarda endotelialit ile seyreden trombüslerin yaygın olarak izlendiği çoklu organ tutulumu olan bir hastalık haline dönüştüğü belirlenmiştir. Diffüz alveolar hasar, ağır endotelyal hasar, mikroanjiopati, vasküler trombozis baskın akciğer bulguları arasındadır. Kardiyovasküler sistemde sıklıkla kardiyomegali ve trombüs ile sinir sisteminde mikrotrombüs varlığı, akut enfarkt, astrogliozis, mikroglial nodüller saptanmıştır. Böbreklerde farklı glomerülonefritler, tübüler hasarlanma, trombotik lezyonlar izlenmiştir. Karaciğerde fibrinöz mikrotrombüs, hepatik steatoz, hafif hepatit bulguları ve portal yangı sık izlenen bulgulardır. İnce barsaklarda ise en sık bulgular mikrotrombüs, nekroz ve lenfositik endotelialittir. Farklı organlarda endotel ve parankim hücrelerinde elektron mikroskopi veya immünhistokimya ile virüs saptanmıştır. Çok sayıda ölüme neden olan pandemide, trombotik süreçlerin fark edilmesi tedavi yaklaşımını etkilemiştir. Gelecekte de hastalığın ve geç dönem etkilerinin anlaşılmasında otopsi bulgularının katkısının süreceği ön görülebilir.

POSTMORTEM AND AUTOPSY FINDINGS OF COVID-19

In the COVID 19 pandemic, within the 15 months after December 2019, when the first case was observed, it has been of great importance to understand the pathophysiology of the disease in order to find treatment. Postmortem examination and autopsy findings revealed that the disease is not only a pulmonary epithelial disease. With autopsy examinations, it has been determined that COVID 19 has turned into a disease with multi organ involvement in which thrombi with endothelialitis is commonly observed in patients especially with poor clinical course. Diffuse alveolar damage, severe endothelial damage, microangiopathy, vascular thrombosis are among the predominant lung findings. In the cardiovascular system cardiomegaly and thrombus, in the nervous system, presence of microthrombus, acute infarction, astrogliosis, microglial nodules have been detected. Different glomerulonephritis, tubular damage, thrombotic lesions were observed in the kidneys. In the liver, fibrinous microthrombus, hepatic steatosis, mild hepatitis findings and portal inflammation are common findings. In the small intestine, most common findings are microthrombus, necrosis and lymphocytic endothelialitis. Virus was detected by electron microscopy or immunohistochemistry in endothelial and parenchymal cells in different organs. The realization of thrombotic processes has affected the treatment approach in the pandemic that causes many deaths. It can be predicted that the contribution of autopsy findings will continue in order to understand the disease and its late effects in the future.

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1. Baral R, Ali O, Brett I, Reinhold J, Vassiliou VS. COVID 19: A pan organ pandemic. Oxford Medical Case Reports. 2020;2020(12):423 9. doi:10.1093/omcr/omaa107.
2. Tabary M, Khanmohammadi S, Araghi F, Dadkhahfar S, Tavangar SM. Pathologic features of COVID 19: A concise review. Pathol Res Pract. 2020;216(9):153097. doi:10.1016/j.prp.2020.153097.
3. Hammoud H, Bendari A, Bendari T, Bougmiza I. Histopathological findings in COVID 19 cases: A systematic review. medRxiv. Published online 2020. doi:10.1101/2020.10.11.20210849.
4. Zhou B, Zhao W, Feng R, Zhang X, Li X, Zhou Y, et al. The pathological autopsy of coronavirus disease 2019 (COVID 2019) in China: a review. Pathog Dis. 2020;78(3):ftaa026. doi:10.1093/femspd/ftaa026.
5. Bian XW;The Covid 19 Pathology Team. Autopsy of COVID 19 victims in China. Natl Sci Rev. 2020;7(9):1414 8. doi:10.1093/nsr/nwaa123.
6. Kommoss FKF, Schwab C, Tavernar L, Schreck J, Wagner WL, Merle U, et al. Pathologie der schweren COVID 19 bedingten Lungenschädigung. Dtsch Arztebl Int. 2020;117(29 30):500 6. doi:10.3238/arztebl.2020.0500.
7. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid 19. New Engl J Med. 2020;383(2):120 8. doi:10.1056/nejmoa2015432.
8. Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, et al. Immunothrombotic dysregulation in COVID 19 pneumonia is associated with respiratory failure and coagulopathy. Circulation. 2020;142(12):1176 89. doi:10.1161/CIRCULATIONAHA.120.048488.
9. Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N, et al. Postmortem examination of COVID 19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198 209. doi:10.1111/his.14134.
10. de Michele S, Sun Y, Yilmaz MM, Katsyv I, Salvatore M, Dzierba AL, et al. Forty Postmortem Examinations in COVID 19 Patients Two Distinct Pathologic Phenotypes and Correlation with Clinical and Radiologic Findings. Am J Clin Pathol. 2020;154(6):748 60. doi:10.1093/ajcp/aqaa156.
11. Falasca L, Nardacci R, Colombo D, Lalle E, Di Caro A, Nicastri E, et al. Postmortem Findings in Italian Patients with COVID 19: A Descriptive Full Autopsy Study of Cases with and without Comorbidities. J Infect Dis. 2020;222(11):1807 15. doi:10.1093/infdis/jiaa578.
12. Nienhold R, Ciani Y, Koelzer VH, Tzankov A, Haslbauer JD, Menter T, et al. Two distinct immunopathological profiles in autopsy lungs of COVID 19. Nat Commun. 2020;11(1):1 13. doi:10.1038/s41467 020 18854 2.
13. Bradley BT, Maioli H, Johnston R, Chaudhryl I, Fink SL, Xu H, et al. Histopathology and ultrastructural findings of fatal COVID 19 infections in Washington State: a case series. Lancet. 2020;396(10247):320 332. doi:10.1016/S0140 6736(20)31305 2.
14. Roden AC, Bois MC, Johnson TF, Aubry MC, Alexander MP, Hagen CE, et al. The spectrum of histopathologic findings in lungs of patients with fatal coronavirus disease 2019 (Covid 19) infection. Arch Pathol Lab Med. 2021;145(1):11 21. doi:10.5858/arpa.2020 0491 SA.
15. Li Y, Wu J, Wang S, Li X, Zhou J, Huang B, et al. Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID 19 pneumonia in Wuhan, China. Histopathology. 2021; 78(4):542 55. doi:10.1111/his.14249.
16. Aesif SW, Bribriesco AC, Yadav R, Nugent SL, Zubkus D, Tan CD, et al. Pulmonary Pathology of COVID 19 Following 8 Weeks to 4 Months of Severe Disease: A Report of Three Cases, Including One With Bilateral Lung Transplantation. Am J Clin Pathol. 2021;155(4):506 14. doi:10.1093/ajcp/aqaa264.
17. Buja LM, Wolf D, Zhao B, Akkanti B, McDonald M, Lelenwa L, et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID 19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol. 2020;48:107233. doi:10.1016/j.carpath.2020.107233.
18. Bösmüller H, Traxler S, Bitzer M, Häberle H, Raiser W, Nann D, et al. The evolution of pulmonary pathology in fatal COVID 19 disease: an autopsy study with clinical correlation. Virchows Archiv. 2020;477(3):349 57. doi:10.1007/s00428 020 02881 x.
19. Lippi G, Lavie CJ, Sanchis Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID 19): Evidence from a meta analysis. Prog Cardiovasc Dis. 2020;63(3):390 1. doi:10.1016/j.pcad.2020.03.001.
20. Elsoukkary SS, Mostyka M, Dillard A, Berman DR, Ma LX, Chadburn A, et al. Autopsy Findings in 32 Patients with COVID 19: A Single Institution Experience. Pathobiology. 2021;88(1):56 68. doi:10.1159/000511325.
21. Bois MC, Boire NA, Layman AJ, Aubry MC, Alexander MP, Roden AC, et al. COVID 19–Associated Nonocclusive Fibrin Microthrombi in the Heart. Circulation. 2021;143(3):230 43. doi:10.1161/circulationaha.120.050754.
22. Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N et al. Postmortem examination of COVID 19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198 209. doi:10.1111/his.14134.
23. Remmelink M, de Mendonça R, D’Haene N, De Clercq S, Verocq C, Lebrun L, et al. Unspecific post mortem findings despite multiorgan 1 viral spread in COVID 19 patients. medRxiv. Published online 2020:1 10. doi:10.1101/2020.05.27.20114363.
24. Gauchotte G, Venard V, Segondy M, Cadoz C, Esposito Fava A, Barraud D, et al. SARS Cov 2 fulminant myocarditis: an autopsy and histopathological case study. Int J Legal Med. 2021; 135(2):577 81. doi:10.1007/s00414 020 02500 z.
25. Titi L, Magnanimi E, Mancone M, Infusino F, Coppola G, Del Nonno F, et al. Fatal Takotsubo syndrome in critical COVID 19 related pneumonia. Cardiovasc Pathol. 2021;51:107314. doi:10.1016/j.carpath.2020.107314.
26. Morgello S. Coronaviruses and the central nervous system. J Neurovirol. 2020;26(4):459 73. doi:10.1007/s13365 020 00868 7.
27. Bryce C, Grimes Z, Pujadas E, Ahujo S, Beasley MB, Albrecht R, et al. Pathophysiology of SARS CoV 2: Targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID 19 autopsy experience. medRxiv. Published online 2020. doi:10.1101/2020.05.18.20099960.
28. Matschke J, Lütgehetmann M, Hagel C, Sperhake JP, Schröder AS, Edler C, et al. Neuropathology of patients with COVID 19 in Germany: a post mortem case series. Lancet Neurol. 2020;19(11):919 29. doi:10.1016/S1474 4422(20)30308 2.
29. Deigendesch N, Sironi L, Kutza M, Wischnewski S, Fuchs V, Hench J, et al. Correlates of critical illnessrelated encephalopathy predominate postmortem COVID 19 neuropathology. Acta Neuropathol. 2020;140(4):583 6. doi:10.1007/s00401 020 02213 y.
30. Mukerji SS, Solomon IH. What can we learn from brain autopsies in COVID 19? Neurosci Lett. 2021;742:135528. doi:10.1016/j.neulet.2020.135528.
31. Pei G, Zhang Z, Peng J, Liu L, Zhang C, Yu C, et al. Renal involvement and early prognosis in patients with COVID 19 pneumonia. J Am Soc Nephrol. 2020;31(6):1157 65. doi:10.1681/ASN.2020030276.
32. 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(5):829 38. doi:10.1016/j.kint.2020.03.005.
33. Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID 19 in China. Kidney Int. 2020;98(1):219 27. doi:10.1016/j.kint.2020.04.003.
34. Kudose S, Batal I, Santoriello D, Xu K, Barasch J, Peleg Y, et al. Kidney Biopsy Findings in Patients with COVID 19. J Am Soc Nephrol. 2020;31(9):1959 68. doi:10.1681/ASN.2020060802.
35. Farkash EA, Wilson AM, Jentzen JM. Ultrastructural evidence for direct renal infection with Sars Cov 2. J Am Soc Nephrol. 2020;31(8):1683 7. doi:10.1681/ASN.2020040432
36. Jonigk D, Märkl B, Helms J. COVID 19: What the clinician should know about post mortem findings. Intensive Care Med. 2021;47(1):86 9. doi:10.1007/s00134 020 06302 0.
37. Schaller T, Hirschbühl K, Burkhardt K, Braun G, Trepel M, Märkl B, et al. Postmortem Examination of Patients with COVID 19. JAMA. 2020;323(24):2518 20. doi:10.1001/jama.2020.8907.
38. Zhao CL, Rapkiewicz A, Maghsoodi Deerwester M, Gupta M, Cao W, Palaia T, et al. Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID 19). Hum Pathol. 2021;109:59 68. doi:10.1016/j.humpath.2020.11.015.
39. Menter T, Haslbauer JD, Nienhold R, et al. Postmortem examination of COVID 19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198 209. doi:10.1111/his.14134.
40. Elsoukkary SS, Mostyka M, Dillard A, Berman DR, Ma LX, Chadburn A, et al. Autopsy Findings in 32 Patients with COVID 19: A Single Institution Experience. Pathobiology. 2021;88(1):56 68. doi:10.1159/000511325.
41. Eketunde AO, Mellacheruvu SP, Oreoluwa P. A Review of Postmortem Findings in Patients With COVID 19. Cureus. 2020;12(7):e9438. doi:10.7759/cureus.9438.
42. Polak SB, Van Gool IC, Cohen D, von der Thüsen JH, van Paassen J. A systematic review of pathological findings in COVID 19: a pathophysiological timeline and possible mechanisms of disease progression. Mod Pathol. 2020;33(11):2128 38. doi:10.1038/s41379 020 0603 3.