Evaluation of postmortem pathological changes in the lung in SARS-CoV-2 RT-PCR positive cases

Year 2021, Volume: 5 Issue: 11, 1113 - 1120, 01.11.2021

Taner Daş Aytül Buğra Murat Nihat Arslan Nihan Ziyade Yalcin Buyuk

https://doi.org/10.28982/josam.997381

Cited By: 1

Abstract

Background/Aim: The most common cause of death in COVID-19 is acute respiratory distress syndrome. Diffuse alveolar damage is the histological characteristic and counterpart of acute respiratory distress syndrome. Histopathological findings, accompanied by immunohistochemical findings, can provide valuable information in the pathogenesis of Covid-19. We aimed to investigate the histopathological findings by supporting our results with immunohistochemical staining in SARS-CoV-2 positive autopsies.
Methods: A total of 101 autopsy cases with positive postmortem SARS-CoV-2 rt-PCR tests between May 2020-May 2021 were investigated in this retrospective cohort study. Cases with negative postmortem swab samples on rt-PCR and those with severe autolysis were excluded from the study. Pathological changes in the lung were examined with hematoxylin and eosin-stained preparations. Immunohistochemical assay with pancytokeratin, TTF-1, IL-6, CD68, CD3, CD8, and antibodies against the SARS-CoV-2 nucleocapsid protein were also performed for further evaluation.
Results: Diffuse alveolar damage findings were present in 58 (61.7%) out of 94 cases in our study. Seventeen (18.1%) showed findings compatible with the exudative phase, 37 (39.3%) were in the proliferative phase, and 4 (4.3%) were in the fibrotic phase of diffuse alveolar damage. Pulmonary perivascular lymphocytic infiltrates contained more CD3 (+) T lymphocytes than CD8 (+) T lymphocytes, immunohistochemically.
Conclusion: The finding of more CD3 positive T lymphocytes than the CD8 positive T lymphocytes in the perivascular lymphocytic infiltrate correlates with the hypothesis of the direct destruction of CD8 (+) T lymphocytes or through impairment of cellular immunity by SARS-CoV-2 induced mediators. Detection of immunohistochemical staining with IL-6 in COVID-19 supports the cytokine storm mentioned in the previous studies and the role of IL-6 in cytokine storm in SARS-CoV-2 infection. The limited number of immunohistochemical studies on SARS-CoV-2 increases the importance of our study, which evaluates IL-6, CD3, and CD8 expressions at the tissue level. Autopsy research is important and contributes to the development of protective, diagnostic, and therapeutic modalities.

Keywords

Autopsy, SARS-CoV-2, COVID-19, IL-6, CD3, CD8

Thanks

We would like to express our endless gratitude to the Council of Forensic Medicine for the permission they gave us to do this work and for their support.

References

• 1. 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.
• 2. Martines RB, Ritter JM, Matkovic E, Gary J, Bollweg BC, Bullock H, et al. Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States. Emerg Infect Dis. 2020;26(9):2005-15. doi: 10.3201/eid2609.202095.
• 3. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3. doi: 10.1038/s41586-020-2012-7.
• 4. Satturwar S, Fowkes M, Farver C, Wilson AM, Eccher A, Girolami I, et al. Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis. Am J Surg Pathol. 2021;45(5):587-603. doi: 10.1097/PAS.0000000000001650.
• 5. Worldometers (2021). COVID-19 coronavirus pandemic [Online]. Website: www.worldometers.info/coronavirus/ [Accessed 17 08 2021].
• 6. Bryce C, Grimes Z, Pujadas E, Ahuja S, Beasley MB, Albrecht R, et al. Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience. Mod Pathol. 2021;34:1456–67. doi:10.1038/s41379-021-00793-y.
• 7. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, et al. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005;33(1):1-6;discussion 230-2. doi: 10.1097/01.ccm.0000149854.61192.dc.
• 8. Kim GW, Lee NR, Pi RH, Lim YS, Lee YM, Lee JM, et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res. 2015;38(5): 575-84. doi: 10.1007/s12272-015-0569-8.
• 9. Stapleton RD, Suratt BT, Neff MJ, Wurfel MM, Ware LB, Ruzinski JT, et al. Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients. Biomarkers. 2019;24(4):352–59. doi:10.1080/1354750X.2019.1581840.
• 10. Chan PK, Chan DP, To KF, Yu MY, Cheung JL, Cheng AF. Evaluation of extraction methods from paraffin wax embedded tissues for PCR amplification of human and viral DNA. J Clin Pathol. 2001;54(5):401-3. doi: 10.1136/jcp.54.5.401.
• 11. Arslan MN, Büyük Y, Ziyade N, Elgörmüş N, Şirin G, Çoban İ, et al. COVID-19 autopsies of Istanbul. Ir J Med Sci. 2021;23:1–13. doi: 10.1007/s11845-021-02602-6.
• 12. Bugra A, Das T, Arslan MN, Ziyade N, Buyuk Y. Postmortem pathological changes in extrapulmonary organs in SARS-CoV-2 rt-PCR-positive cases: a single-center experience. Ir J Med Sci. 2021;7:1–11. doi: 10.1007/s11845-021-02638-8.
• 13. Vasquez-Bonilla WO, Orozco R, Argueta V, Sierra M, Zambrano LI, Muñoz-Lara F, et al. A review of the main histopathological findings in coronavirus disease 2019. Hum Pathol. 2020;105:74–83. doi: 10.1016/j.humpath.2020.07.023.
• 14. Gencer S, Lacy M, Atzler D, an der Vorst EPC, Döring Y, Weber C. Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19. Thromb Haemost. 2020;120(12):1629-41. doi: 10.1055/s-0040-1718735.
• 15. Borczuk AC, Salvatore SP, Seshan SV, Patel SS, Bussel JB, Mostyka M. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol. 2020;33(11):2156-68. doi: 10.1038/s41379-020-00661-1.
• 16. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383:120–8. doi: 10.1056/NEJMoa2015432.
• 17. Cheung OY, Graziano P, Leslie KO. Acute Lung Injury. In: Leslie KO, Wick MR, eds. Practical Pulmonary Pathology: A Diagnostic Approach, 3rd edn. Philadelphia, PA, USA: Elsevier; 2018. pp 125-46.
• 18. Franks TJ, Chong PY, Chui P, Galvin JR, Lourens RM, Reid AH, et al. Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore. Hum Pathol. 2003;34(8):743-8. doi: 10.1016/s0046-8177(03)00367-8.
• 19. Brune K, Frank J, Schwingshackl A, Finigan J, Sidhaye VK. Pulmonary epithelial barrier function: some new players and mechanisms. Am J Physiol Lung Cell Mol Physiol. 2015;08(8):L731-45. doi: 10.1152/ajplung.00309.2014.
• 20. Mehta P, McAuley DF, Brown M, Finigan J, Sidhaye VK, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-34. doi: 10.1016/S0140-6736(20)30628-0.
• 21. Calabrese F, Pezzuto F, Fortarezza F, Hofman P, Kern I, Panizo A, et al. Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Virchows Arch. 2020;477(3):359-72. doi: 10.1007/s00428-020-02886-6.
• 22. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123-30. doi: 10.1080/22221751.2020.1770129.
• 23. Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53:13-24. doi: 10.1016/j.cytogfr.2020.05.009.
• 24. Frisoni P, Neri M, D'Errico S, Alfieri L, Bonuccelli D, Cingolani M, et al. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Sci Med Pathol. 2021;31:1–15. doi: 10.1007/s12024-021-00414-9.
• 25. Mor F, Cohen IR. IL-2 rescues antigen-specific T cells from radiation or dexamethasone-induced apoptosis. Correlation with induction of Bcl-2. J Immunol. 1996;156(2):515-22.
• 26. Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. EClinicalMedicine. 2020;24:100434. doi: 10.1016/j.eclinm.2020.100434.
• 27. Huang JL, Huang J, Duan ZH, Wei J, Min J, Luo XH, et al. Th2 predominance and CD8+ memory T cell depletion in patients with severe acute respiratory syndrome. Microbes Infect. 2005;7(3):427-36. doi: 10.1016/j.micinf.2004.11.017.
• 28. Valdivia-Mazeyra MF, Salas C, Nieves-Alonso JM, Martín-Fragueiro L, Bárcena C, Muñoz-Hernández P, et al. Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature. Virchows Arch. 2021;478(3):487-96. doi: 10.1007/s00428-020-02926-1.
• 29. Washington AV, Esponda O, Gibson A. Platelet biology of the rapidly failing lung. Br J Haematol. 2020;188(5):641-51. doi: 10.1111/bjh.16315.
• 30. Yadav H, Kor DJ. Platelets in the pathogenesis of acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2015;309(9):L915-23. doi: 10.1152/ajplung.00266.2015.
• 31. Mandal RV, Mark EJ, Kradin RL. Megakaryocytes and platelet homeostasis in diffuse alveolar damage. Exp Mol Pathol. 2007;83(3):327-31. doi: 10.1016/j.yexmp.2007.08.005.
• 32. Wells S, Sissons M, Hasleton PS. Quantitation of pulmonary megakaryocytes and fibrin thrombi in patients dying from burns. Histopathology. 1984;8(3): 517-27. doi: 10.1111/j.1365-2559.1984.tb02361.x.
• 33. Tombolini A, Scendoni R. SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns. Int J Legal Med. 2020;134(6): 2205-8. doi: 10.1007/s00414-020-02354-5.
• 34. Jackson NR, Zeigler K, Torrez M, Makino Y, Adolphi NL, Lathrop S, et al. New Mexico's COVID-19 Experience. Am J Forensic Med Pathol. 2020;42(1):1-8. doi: 10.1097/PAF.0000000000000664.
• 35. Daş T, Sargan A, Yağmur G, Yildirim M, Topal CS, Gürler AS, et al. Viral Pneumonias in Forensic Autopsies: Evaluation and Classification of Histopathologic Changes With Microbiologic Correlation. Am J Forensic Med Pathol. 2016;37(4):255-63. doi: 10.1097/PAF.0000000000000261.
• 36. Lacy JM, Brooks EG, Akers J, Armstrong D, Decker L, Gonzalez A, et al. COVID-19: Postmortem Diagnostic and Biosafety Considerations. Am J Forensic Med Pathol. 2020;41(3):143-51. doi: 10.1097/PAF.0000000000000567.
• 37. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X.
• 38. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol. 2020;15(5):700-4. doi: 10.1016/j.jtho.2020.02.010.