Lungs of COVID-19 affected patients: an autoptic morphological profile

Giovanni Tuccari, Gaetano Caramori, Vittorio Cavallari, Guido Fadda, Antonio Ieni

Abstract


Current knowledge concerning the recently occurred Coronavirus disease 2019 (COVID-19) is largely based on human and laboratory reports, even if pathogenic mechanisms have been greatly elucidated by autoptic procedures. Consequently, the aim of this study is to describe macroscopic changes and histopathological findings documented in lung tissue of these patients. Moreover, the need of an optimised autopsy protocol and the application of ancillary techniques, such as immunohistochemistry (IlHC), in situ hybridization (ISH), PCR-based assay and electron microscopy, have to be recorded in order to assess the presence of COVID-19 virus-like particles in lung tissue, although the risk of autolytic changes as well the incorrect interpretation of artefacts should be cautiously considered.

Keywords


Coronavirus, autopsy, lung tissue, alveoli, endothelial cells, viral-like particles

Full Text:

PDF

References


1. Wu, F., Zhao, S., Yu, B., Chen, Y.M., Wang, W., Song, Z.G., Hu, Y., Tao, Z.W., Tian, J.H., Pei, Y.Y., Yuan, M.L., Zhang, Y.L., Dai, F.H., Liu, Y., Wang, Q.M., Zheng. J.J., Xu. L., Holmes, E.C., Zhang, Y.Z., (2020) A new coronavirus associated with human respiratory disease in China.Nature; 579 (7798): 265-269.

2. Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., Si, H.R., Zhu, Y., Li, B., Huang, C.L., Chen, H.D., Chen, J., Luo, Y., Guo, H., Jiang, R.D., Liu, M.Q., Chen, Y., Shen, X.R., Wang, X., Zheng, X.S., Zhao, K., Chen, Q.J., Deng, F., Liu, L.L., Yan, B., Zhan, F.X., Wang, Y.Y., Xiao, G.F., Shi, Z.L., (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature; 579 (7798):270-273.

3. Zhang, T., Wu, Q., Zhang, Z., (2020) Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak.Curr Biol; 30 (8):1578.

4. Calabrese, F., Pezzuto, F., Fortarezza, F., Hofman, P., Kern, I., Panizo, A., von der Thüsen, J., Timofeev, S., Gorkiewicz, G., Lunardi, F., (2020) Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists.Virchows Arch, 477 (3):359-372.

5. Guan, W.J., Ni. Z.Y., Hu. Y., Liang. W.H., Ou. C.Q., He. J.X., Liu. L., Shan. H., Lei. C.L., Hui. D.S.C., Du, B., Li, L.J., Zeng, G., Yuen. K.Y., Chen, R.C., Tang, C.L., Wang, T., Chen, P.Y., Xiang, J., Li, S.Y., Wang, J.L., Liang, Z.J., Peng, Y.X., Wei, L., Liu, Y., Hu, Y.H., Peng, P., Wang, J.M., Liu, J.Y., Chen, Z., Li, G., Zheng, Z.J., Qiu, S.Q,, Luo, J., Ye, C.J., Zhu, S.Y., Zhong, N.S.; China Medical Treatment Expert Group for Covid-19., (2020) Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med; 382 (18):1708-1720.

6. Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Gao, H., Guo, L., Xie, J., Wang, G., Jiang, R., Gao, Z., Jin, Q., Wang, J., Cao, B., (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet; 395 (10223):497-506.

7. Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., Zhao, Y., Li, Y., Wang, X., Peng, Z., (2020) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.JAMA; 323(11):1061-1069.

8. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY., (2020) Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. .JThorac Oncol; 15 (5):700-704.

9. Menter, T., Haslbauer, J.D., Nienhold, R., Savic, S., Hopfer, H., Deigendesch, N., Frank, S., Turek, D., Willi, N., Pargger, H., Bassetti, S., Leuppi, J.D., Cathomas, G., Tolnay, M., Mertz, K.D., Tzankov, A., (2020) 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; 77 (2):198-209.

10. Barbareschi, M., Ascoli, V., Bonoldi, E., Cavazza, A., Colombari, R., Cozzi, I., Dainese, E., Facchetti, F., Fadda, G., Ferrara, G., Fraggetta, F., Graziano, P., Murer, G., Rossi, E.D., Rossi, G., Negri, G., Zannoni, G., Sapino, A., (2020) Biosafety in surgicalpathology in the era of SARS-Cov2 pandemia. A statement of the Italian Society of Surgical Pathology and Cytology. Pathologica; 112 (2):59-63.

11. Fineschi, V., Aprile, A., Aquila, I., Arcangeli, M., Asmundo, A., Bacci, M., Cingolani, M., Cipolloni, L., D'Errico, S., De Casamassimi, I., Di Mizio, G., Di Paolo, M., Focardi, M., Frati, P., Gabbrielli, M., La Russa, R., Maiese, A., Manetti, F., Martelloni, M., Mazzeo, E., Montana, A., Neri, M., Padovano, M., Pinchi, V., Pomara, C., Ricci, P., Salerno, M., Santurro, A., Scopetti, M., Testi, R., Turillazzi, E., Vacchiano, G.; Scientific Society of Hospital Legal Medicine of the National Health System (COMLAS), Crivelli, F., Bonoldi, E., Facchetti, F., Nebuloni, M., Sapino, A; Italian Society of Anatomical Pathology and Cytology (SIAPEC)., (2020) Management of the corpse with suspect, probable or confirmed COVID-19 respiratory infection - Italian interim recommendations for personnel potentially exposed to material from corpses, including body fluids, in morgue structures and during autopsy practice.Pathologica; 112 (2):64-77.

12. Hanley, B., Lucas, S.B., Youd, E., Swift, B., Osborn, M., (2020) Autopsy in suspected COVID-19 cases.J Clin Pathol; 73 (5):239-242

13. Castillo, P., Martínez, M.J., Ussene, E., Jordao, D., Lovane, L., Ismail, M.R., Carrilho, C., Lorenzoni, C., Fernandes, F., Bene, R., Palhares, A., Ferreira, L., Lacerda, M., Mandomando, I., Vila, J., Hurtado, J.C., Munguambe, K., Maixenchs, M., Sanz, A., Quintó, L., Macete, E., Alonso, P., Bassat, Q., Menéndez, C., Ordi, J., (20169 Validity of a Minimally Invasive Autopsy for Cause of Death Determination in Adults in Mozambique: An Observational Study.PLoS Med; 13 (11):e1002171.

14. Aguiar, D., Lobrinus, J.A., Schibler, M., Fracasso, T., Lardi, C., (2020) Inside the lungs of COVID-19 disease. Int J Legal Med; 134 (4):1271-1274.

15. Buja, L.M., Wolf, D.A., Zhao, B., Akkanti, B., McDonald, M., Lelenwa, L., Reilly, N., Ottaviani, G., Elghetany, M.T., Trujillo, D.O., Aisenberg, G.M., Madjid, M., Kar, B., (2020) 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; 48:107233.

16. Fox, S.E., Akmatbekov, A., Harbert, J.L., Li, G., Quincy Brown, J., Vander Heide, RS., (2020) Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans.Lancet Respir Med; 8 (7):681-686.

17. Grimes, Z., Bryce, C., Sordillo, E.M., Gordon, R.E., Reidy, J., PanizMondolfi, A.E., Fowkes, M., (2020) Fatal Pulmonary Thromboembolism in SARS-CoV-2-Infection.Cardiovasc Pathol; 48:107227.

18. Konopka, K.E., Wilson, A., Myers, J.L., (2020) Postmortem Lung Findings in a Patient With Asthma and Coronavirus Disease 2019.Chest; 158 (3):e99-e101.

19. Lacy, J.M., Brooks, E.G., Akers, J., Armstrong, D., Decker, L., Gonzalez, A., Humphrey, W., Mayer, R., Miller, M., Perez, C., Arango, J.A.R., Sathyavagiswaran, L., Stroh, W., Utley, S., (2020) COVID-19: Postmortem Diagnostic and Biosafety Considerations.Am J Forensic Med Pathol; 41 (3):143-151.

20. Lax, S.F., Skok, K., Zechner, P., Kessler, H.H., Kaufmann, N., Koelblinger, C., Vander, K., Bargfrieder, U., Trauner, M., (2020) Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome : Results From a Prospective, Single-Center, Clinicopathologic Case Series.Ann Intern Med; 173 (5):350-361.

21. Wichmann, D., Sperhake, J.P., Lütgehetmann, M., Steurer, S., Edler, C., Heinemann, A., Heinrich, F., Mushumba, H., Kniep, I., Schröder, A.S., Burdelski, C., de Heer, G., Nierhaus, A., Frings, D., Pfefferle, S., Becker, H., Bredereke-Wiedling, H., de Weerth, A., Paschen, H.R,.Sheikhzadeh-Eggers, S., Stang, A,.Schmiedel, S., Bokemeyer, C., Addo, M.M., Aepfelbacher, M., Püschel. K., Kluge. S., (2020) Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.Ann Intern Med;173 (4):268-277

22. Yan, L., Mir, M., Sanchez, P., Beg, M., Peters, J., Enriquez, O., Gilbert, A., (2020) OVID-19 in a Hispanic Woman.Arch Pathol Lab Med; 144 (9):1041-1047.

23. Barton, L.M., Duval, E.J., Stroberg, E., Ghosh, S., Mukhopadhyay, S., (2020) COVID-19 Autopsies, Oklahoma, USA.Am J Clin Pathol; 153 (6):725-733.

24. Bösmüller, H., Traxler, S., Bitzer, M., Häberle, H., Raiser, W., Nann, D., Frauenfeld, L., Vogelsberg, A., Klingel, K., Fend, F., (2020) The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation.Virchows Arch; 477 (3):349-357.

25. Tombolini, A., Scendoni, R., (2020) SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns.Int J Legal Med; 29:1-4.

26. Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., Tai, Y., Bai, C., Gao, T., Song, J., Xia, P., Dong, J., Zhao, J., Wang, F.S., (2020) Pathological findings of COVID-19 associated with acute respiratory distress syndrome.Lancet Respir Med; 8 (4):420-422.

27. Connors, J.M., Levy. J.H., (2020) COVID-19 and its implications for thrombosis and anticoagulation.Blood;135 (23):2033-2040.

28. Llitjos, J.F., Leclerc, M., Chochois, C., Monsallier, J.M., Ramakers, M., Auvray, M., Merouani, K.J., (2020) High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. Thromb Haemost;18 (7):1743-1746.

29. Spiezia, L., Boscolo, A., Poletto, F., Cerruti, L., Tiberio, I., Campello, E., Navalesi, P., Simioni, P., ( 2020) COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure.ThrombHaemost; 120 (6):998-1000.

30. Varga, Z., Flammer, A.J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A.S., Mehra, M.R., Schuepbach. R.A., Ruschitzka, F., Moch, H., (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet; 395 (10234):1417-1418.

31. Li, H., Liu, L., Zhang, D., Xu, J., Dai, H., Tang, N., Su, X., Cao, B., (2020) SARS-CoV-2 and viral sepsis: observations and hypotheses.Lancet; 395 (10235):1517-1520.

32. Liu, J., Babka, A.M., Kearney, B.J., Radoshitzky, S.R., Kuhn, J.H., Zeng, X., (2020) Molecular detection of SARS-CoV-2 in formalin-fixed, paraffin-embedded specimens.JCI Insight; 5 (12):e139042

33. Adachi, T., Chong, J.M., Nakajima, N., Sano, M., Yamazaki, J., Miyamoto, I., Nishioka, H., Akita, H., Sato, Y., Kataoka, M., Katano, H., Tobiume, M., Sekizuka, T., Itokawa, K., Kuroda, M., Suzuki T., (2020) Clinicopathologic and Immunohistochemical Findings from Autopsy of Patient with COVID-19, Japan.Emerg Infect Dis; 26 (9):2157-61.

34. Facchetti, F., Bugatti, M., Drera, E., Tripodo, C., Sartori, E., Cancila, V., Papaccio, M., Castellani, R., Casola, S., Boniotti, M.B., Cavadini, P., Lavazza, A., (2020) SARS-CoV2 vertical transmission with adverse effects on the newborn revealed through integrated immunohistochemical, electron microscopy and molecular analyses of placenta.EBioMedicine; 59:102951.

35. Guerini-Rocco, E., Taormina, S.V., Vacirca, D., Ranghiero, A., Rappa, A., Fumagalli, C., Maffini, F., Rampinelli, C., Galetta, D., Tagliabue, M., Ansarin, M., Barberis, M., (2020) SARS-CoV-2 detection in formalin-fixedparaffin-embedded tissuespecimens from surgicalresection of tonguesquamouscell carcinoma.J Clin Pathol: jclinpath-2020-206635.

36. Farkash, E.A., Wilson, A.M., Jentzen, J.M., (2020) Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2. J Am Soc Nephrol; 31 (8):1683-1687.

37. Goldsmith, C.S., Miller, S.E., Martines, R.B., Bullock. H.A., Zaki, S.R., (2020) Electron microscopy of SARS-CoV-2: a challenging task. Lancet; 395 (10238):e99.

38. Prasad, S., Potdar, V., Cherian, S., Abraham, P., Basu, A.; ICMR-NIV NIC Team., (2020) Transmission electron microscopy imaging of SARS-CoV-2.. Indian J Med Res; 151 (2&3):241-243.

39. Ackermann, M., Verleden, S.E., Kuehnel, M., Haverich, A., Welte, T., Laenger, F., Vanstapel, A., Werlein, C., Stark, H., Tzankov, A., Li, W.W., Li, V.W., Mentzer, S.J., Jonigk, D., (2020) Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med; 383 (2):120-128.




DOI: https://doi.org/10.6092/1828-6550/APMB.108.2.2020.SD5

Refbacks

  • There are currently no refbacks.


Copyright (c) 2020 Giovanni Tuccari, Gaetano Caramori, Vittorio Cavallari, Guido Fadda, Antonio Ieni

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.