Pulmonary pathology of the new coronavirus disease (COVID-19). The preliminary analysis of post-mortem findings

Cover Page

Cite item

Full Text

Abstract

Background. Currently, the patho- and morphogenesis of the new coronavirus infection (COVID-19) is being studied in depth. A comparative analysis of the morphological changes in the lungs of deceased patients is of importance, for various time periods after the onset of the first clinical symptoms. The clinical and morphological comparison should help to increase the qualified medical care for patients in the resuscitation profile and reduce the hospital mortality.

The aim of the study was to formulate a working hypothesis for a conceptual scheme of clinical and morphological phases of development of the new coronavirus infection (COVID-19).

Methods. An analysis of 80 fatal cases was carried out in the COVID-center of the Federal Research Clinical Center of FMBA of Russia. Along with the assessment of macro- and microscopic changes in the respiratory tract, additional histochemical van Gieson staining was applied and immunohistochemical studies were performed to assess the condition of the COVID-19-affected lungs.

Results. The revealed features of diffuse alveolar damage in the case of the new coronavirus infection (COVID-19) made it possible to present a working hypothesis of the pathomorphogenesis of COVID-19 interstitial pneumonia. It proceeds through 3 phases: fulminant, persistent and fibrotic. Each phase is conditionally limited by certain time parameters and is characterized by certain morphological signs Dysregulatory activation of monocytic phagocytes, development of generalized microthrombosis, persistent signs of the exudative phase, pathological repair, progressive intraalveolar and interstitial fibrosis are the main links in the pathomorphogenesis of COVID-19 interstitial pneumonia. In response to the penetration of SARS-CoV-2, the T-cell immunity reactions prevail at the exudative and proliferative stages. At the fibrotic stage, the overall number of T-lymphocytes is drastically decreased, the cells of humoral immunity are not revealed. The CD8+ T-lymphocytes prevailing over CD4+ T-lymphocyte helpers is probably related to the autoimmune damage mechanisms.

Conclusions. Damage to the lungs with the development of COVID-19 interstitial pneumonia is the main cause of the severe course of the disease and deaths. The revealed features of the pathomorphogenesis of the clinical and morphological phases of COVID-19 interstitial pneumonia will improve the quality of diagnosis and treatment of a new coronavirus infection (COVID-19).

About the authors

Fedor G. Zabozlaev

Federal Research Clinical Center of the Federal Medical-Biological Agency of Russia

Author for correspondence.
Email: fzab@mail.ru
ORCID iD: 0000-0002-7445-8319
SPIN-code: 3259-9332

MD PhD The Head of pathology department of Federal Research Clinical Center FMBA of Russia. 

Russian Federation, 28, Orekhovy boulevard, Moscow, 115682

Eduard V. Kravchenko

Federal Research Clinical Center of the Federal Medical-Biological Agency of Russia

Email: patan-st@mail.ru
ORCID iD: 0000-0001-7317-2602

MD

Russian Federation, 28, Orekhovy boulevard, Moscow, 115682

Anasasia R. Gallyamova

Federal Research Clinical Center of the Federal Medical-Biological Agency of Russia

Email: kick-ass_13@mail.ru
ORCID iD: 0000-0001-7437-3270

врач-патологоанатом

Russian Federation, 28, Orekhovy boulevard, Moscow, 115682

Nikolay N. Letunovsky

Federal Research Clinical Center of the Federal Medical-Biological Agency of Russia

Email: mortale@mail.ru
ORCID iD: 0000-0003-0004-1016

MD

Russian Federation, 28, Orekhovy boulevard, Moscow, 115682

References

  1. Постановление Главного государственного санитарного врача РФ от 22 мая 2020 г. № 15 «Об утверждении санитарно-эпидемиологических правил СП 3.1.3597-20 «Профилактика новой коронавирусной инфекции (COVID-19)»» [Resolution of the Chief State Sanitary Doctor of the Russian Federation № 15 “Ob utverzhdenii sanitarno-epidemiologicheskikh pravil SP 3.1.3597-20 “Profilaktika novoy koronavirusnoy infektsii (COVID-19)”” dated 2020 May 22. (In Russ).] Доступно по: https://www.garant.ru/products/ipo/prime/doc/74077903/. Ссылка активна на 12.05.2020.
  2. Цинзерлинг В.А., Вашукова М.А., Васильева М.В., и др. Вопросы патоморфогенеза новой коронавирусной инфекции (COVID-19) // Журнал инфектологии. — 2020. — Т.12. — №2. — С. 5–11. [Zinserling VA, Vashukova MA, Vasilyeva MV, et al. Issues of pathology of a new coronavirus infection CoVID-19. Journal Infectology. 2020;12(2):5–11. (In Russ).] doi: 10.22625/2072-6732-2020-12-2-5-11.
  3. Cамсонова М.В., Михалева Л.М., Черняев А.Л., и др. Патологическая анатомия легких при COVID-19: атлас / Под ред. О.В. Зайратьянца. — Рязань: Рязанская областная типография, 2020. — 57 с. [Camsonova MV, Mikhaleva LM, Chernyayev AL, et al. Patologicheskaya anatomiya legkikh pri COVID-19: atlas. Ed. by O.V. Zayrat’yants. Ryazan’: Ryazanskaya oblastnaya tipografiya; 2020. 57 p. (In Russ).]
  4. Singhal TA. Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020;87(4):281–286. doi: 10.1007/s12098-020-03263-6.
  5. Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel Coronavirus Diseases (COVID-19) – China. (In Chinese)]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145–151. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003.
  6. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–269. doi: 10.1038/s41586-020-2008-3.
  7. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: 10.1016/S2213-2600(20)30076-X.
  8. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
  9. Kuster GM, Pfister O, Burkardet T, et al. SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? Eur Heart J. 2020;41(19):1801–1803. doi: 10.1093/eurheartj/ehaa235.
  10. Ocaranza MP, Riquelme JA, Garcia L, et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol. 2020;17(2):116–129. doi: 10.1038/s41569-019-0244-8.
  11. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;e201017. doi: 10.1001/Jamacardio. 2020.1017.
  12. Zhang H, Penninger JM, Li Y, et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46:586–590. doi: 10.1007/s00134-020-05985-9.
  13. Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637. doi: 10.1002/path.1570.
  14. Heurich A, Hofmann-Winkler H, Gierer S, et al. TMPRSS2 and ADAM17 Cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory Syndrome Coronavirus spike protein. J Virol. 2014;88(2):1293–1307. doi: 10.1128/JVI.02202-13.
  15. Tian X, Li C, Huang A, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9(1):382–385. doi: 10.1080/22221751.2020.1729069.
  16. Coronavirus: Novel Coronavirus (COVID-19) Infection. Reviewed by: Perlman S, MD, PhD (Professor Department of Microbiology and 38 Immunology Department of Pediatrics University of Iowa). Published February 5, 2020; Updated 2020 March 25. Elsevier; 2020. 10 p.
  17. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8. doi: 10.1038/s41368-020-0074-x.
  18. Magrone T, Magrone M, Jirillo E. Focus on receptors for Coronaviruses with special reference to angiotensin-converting Enzyme 2 as a potential drug target- a perspective. Endocr Metab Immune Disord Drug Targets. 2020. doi: 10.2174/1871530320666200427112902.
  19. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi: 10.1126/science.abb2507.
  20. Абатуров А.Е., Агафонова Е.А., Кривуша Е.Л., Никулина А.А. Патогенез COVID-19 // Здоровье ребенка. — 2020. — Т.15. — №2. — С. 133–144. [Abaturov AE, Agafonova EA, Krivusha EL, Nikulina AA. Pathogenesis of COVID-19. Zdorovʹe rebenka. 2020;15(2):133–144. (In Russ).] doi: 10.22141/2224-0551.15.2.2020.200598.
  21. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 Patiens with sever respiratory failure. Cell Host Microbe. 2020;27(6):992–1000. doi: 10.1016/j.chom.2020.04.009.
  22. Astuti I, Ysrafil. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab Syndr. 2020;18;14(4):407–412. doi: 10.1016/j.dsx.2020.04.020.
  23. Qin, C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;ciaa248. doi: 10.1093/cid/ciaa248.
  24. Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517–1520. doi: 10.1016/S0140-6736(20)30920-X.
  25. Ruan Q, Yang K, Wang W, et al. 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. doi: 10.1007/s00134-020-05991-x.
  26. Вартанян А.А., Косоруков В.С. Пироптоз — воспалительная форма клеточной гибели // Клиническая онкогематология. — 2020. — Т.13. — №2. — С. 129–135. [Vartanyan AA, Kosorukov VS. Pyroptosis as inflammatory cell death. Clinical oncohematology. 2020;13(2):129–135. (In Russ).] doi: 10.21320/2500-2139-2020-13-2-129-135.
  27. Jeremy KY, Moriyama M, Iwasaki A. Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J Immunol. 2020;ji2000513. doi: 10.4049/jimmunol.2000513.
  28. Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–362. doi: 10.1038/s41577-020-0331-4.
  29. Франк Г.А., Ковалев А.В., Грибунов Ю.П., и др. Исследование умерших с подозрением на коронавирусную инфекцию (COVID-19). Временные методические рекомендации МЗ РФ. Версия 15 (30.04.2020). — М., 2020. — 256 с. [Frank GA, Kovalev AV, Gribunov YuP, et al. Issledovaniye umershikh s podozreniyem na koronavirusnuyu infektsiyu (COVID-19). Vremennyye metodicheskiye rekomendatsii MZ RF. Version 15 (30.04.2020). Moscow; 2020. 256 p. (In Russ).]
  30. Зайцев А.А., Чернов С.А., Стец В.В., и др. Алгоритмы ведения пациентов с новой коронавирусной инфекцией COVID-19 в стационаре. Методические рекомендации. — М.: ГВКГ имени Н.Н. Бурденко, 2020. — 16 с. [Zaytsev AA, Chernov SA, Stets VV, et al. Algoritmy vedeniya patsiyentov s novoy koronavirusnoy infektsiyey COVID-19 v statsionare. Metodicheskiye rekomendatsii. Moscow: Main Military Clinical Hospital N.N. Burdenko; 2020. 16 p. (In Russ).]
  31. Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020.
  32. Katzenstein А.-L.A. Diagnostic atlas of non-neoplastic lung disease: a practical guide for surgical pathologists, NY: Demos Medical Publishing, LLC/Springer Publishing Company; 2016. Р. 115–126.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Basal cell hyperplasia of the tracheal epithelium. Staining with hematoxylin and eosin, × 100

Download (292KB)
Indexing metadata
3. Fig. 2. Macroscopic picture of the lungs in the fulminant phase of COVID-19-interstitial pneumonia, 9-10th days of illness

Download (354KB)
Indexing metadata
4. Fig. 3. Pathomorphological phases of COVID-19-interstitial pneumonia corresponding to exudative (1-5) and proliferative (6-9) stages of acute respiratory distress syndrome (designations 1-9 are given in the text) [illustration by F.G. Zabozlaeva]

Download (497KB)
Indexing metadata
5. Fig. 4. Microscopic picture of the alveoli in the fulminant phase of COVID-19-interstitial pneumonia. Staining with hematoxylin and eosin, × 100

Download (665KB)
Indexing metadata
6. Fig. 5. Pathomorphological changes in the vessels of the lungs in the fulminant phase of COVID-19-interstitial pneumonia. Hematoxylin and eosin staining

Download (599KB)
Indexing metadata
7. Fig. 6. Immunohistochemical analysis of lung changes in the fulminant phase of COVID-19-interstitial pneumonia

Download (1MB)
Indexing metadata
8. Fig. 7. Macro- and microscopic picture of the lungs in the persistent phase of COVID-19-interstitial pneumonia, 18th day of illness. Hematoxylin and eosin staining, × 100 (B, C, D, E); staining according to Van Gieson, × 100 (D)

Download (1MB)
Indexing metadata
9. Fig. 8. Immunohistochemical analysis of lung changes in the persistent phase of COVID-19-interstitial pneumonia

Download (1MB)
Indexing metadata
10. Fig. 9. Macro- and microscopic picture, immunohistochemical analysis of lung changes in the fibrotic phase of COVID-19-interstitial pneumonia, 36th day of illness. Staining with hematoxylin and eosin, × 100 (B, D – E); staining according to Van Gieson, × 100 (V)

Download (1MB)
Indexing metadata
11. Fig. 10. Pathomorphology of the fibrotic phase of COVID-19-interstitial pneumonia

Download (197KB)
Indexing metadata
12. Fig. 11. Stages of acute respiratory distress syndrome according to Anna-Luise A. Katzenstein, 2016 [32]

Download (185KB)
Indexing metadata
13. Fig. 12. Stages of acute respiratory distress syndrome corresponding to the development phases of COVID-19-interstitial pneumonia

Download (251KB)
Indexing metadata

Copyright (c) 2020 Zabozlaev F.G., Kravchenko E.V., Gallyamova A.R., Letunovsky N.N.

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

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies