Histopathology and Pathogenesis of Coronavirus disease 2019 (COVID-19)
Nikolaos Chrysanthakopoulos
Abstract
A severe pandemic of CoronaVirus disease 2019 (COVID-19), according to World Health Organization (WHO), appeared in China in December 2019, and spread rapidly. The majority of the patients had mild symptoms and good prognosis after recovery; however some patients developed severe inflammatory reaction and passed away from multiple organ complications. The novel coronavirus, Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a beta-coronavirus and is similar with the Severe Acute Respiratory Syndrome Corona Virus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). SARS-CoV-2 and -1 have the same host receptor, the angiotensin-converting enzyme 2 (ACE2). The pathogenesis of SARS-CoV-2 infection in humans remains unclear. The immune response is essential to control and reduce SARS-CoV-1 and -2 infections, however, irregular and exaggerated immune responses may lead to the immunopathology of the disease and the lung lesions. This article presents the immunological features of SARS-CoV-2 infection and its potential pathogenesis based on the recent observations of the International literature.
Keywords
References
1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33. doi: 10.1056/NEJMoa2001017.
2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-74. doi: 10.1016/S0140-6736(20)30251-8.
3. Spiegel M, Pichlmair A, Martinez‐Sobrido L, Cros J, García-Sastre A, Haller O, et al. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two‐step model for activation of interferon regulatory factor 3. J Virol. 2005;79(4):2079‐86. doi: 10.1128/JVI.79.4.2079-2086.2005.
4. Kopecky‐Bromberg SA, Martinez‐Sobrido L, Frieman M, Baric RA, Palese P. Severe acute respiratory syndrome coronavirus open reading frame (ORF)
3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 2007;81(2):548‐57. doi: 10.1128/JVI.01782-06.
5. Lu X, Pan J, Tao J, Guo D. SARS‐CoV nucleocapsid protein antagonizes IFN‐beta response by targeting initial step of IFN‐beta induction pathway, and its C‐terminal region is critical for the antagonism. Virus Genes. 2011;42(1):37‐45. doi: 10.1007/s11262-010-0544-x.
6. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368(6490):473-4. doi: 10.1126/science.abb8925.
7. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-9. doi: 10.1172/JCI137244.
8. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;6(5):846-8. doi: 10.1007/s00134-020-05991-x.
9. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA 2020. doi: 10.1001/jama.2020.2648.
10. Crayne CB, Albeituni S, Nichols KE, Cron RQ. The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019;10:119. doi: 10.3389/fimmu.2019.00119.
11. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424-32. doi: 10.1002/jmv.25685.
12. Van der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJ, Wolthers KC, et al. Identification of a new human coronavirus. Nat Med. 2004;10(4):368-73. doi: 10.1038/nm1024.
13. Woo PC, Lau SK, Chu CM, Chan KH, Tsoi HW, Huang Y, et al. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol. 2005;79(2):884-95. doi: 10.1128/JVI.79.2.884-895.2005.
14. Gorbalenya A, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, et al. The species Severe acute respiratory syndrome related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. Nat Micr. 2020;5(4):536-44. doi: 10.1038/s41564-020-0695-z.
15. de Groot RJ, Baker SC, Baric R, Enjuanes L, Gorbalenya AE, Holmes KV, et al. Family coronaviridae. In: King AMS, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus Taxonomy, Classification and Nomenclature of Viruses. Ninth Report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier Academic Press; 2012:806-28.
16. Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting Interleukin-6 Signaling in Clinic. Immunity. 2019;50(4):1007-23. doi: 10.1016/j.immuni.2019.03.026.
17. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959-70. doi: 10.2217/imt-2016-0020.
18. 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(5):475-81. doi: 10.1016/S2213-2600(20)30079-5.
19. Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15(11):1009-16. doi: 10.1038/ni.3002.
20. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quiñones-Falconi F, Bautista E, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361(7):680-9. doi: 10.1056/NEJMoa0904252.
21. Chu H, Zhou J, Wong BH, Li C, Chan JF, Cheng ZS, et al. Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways. J Infect Dis. 2016;213(6):904-14 . doi: 10.1093/infdis/jiv380.
22. Law HK, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, et al. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005;106(7):2366-74. doi: 10.1182/blood-2004-10-4166.
23. 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(5):533-535. doi: 10.1038/s41423-020-0402-2.
24. 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.
25. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. doi: 10.1056/NEJMoa2002032.
26. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE2, a novel homologue of angiotensin converting enzyme. FEBS Letters. 2002;532(1-2):107-10. doi: 10.1016/s0014-5793(02)03640-2.
27. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562-9. doi: 10.1038/s41564-020-0688-y.
28. Mossel EC, Wang J, Jeffers S, Edeen KE, Wang S, Cosgrove GP, et al. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology 2008:372(1):127-135. doi: 10.1016/j.virol.2007.09.045.
29. Weinheimer VK, Becher A, Tonnies M, Holland G, Knepper J, Bauer TT, et al. Influenza A viruses target type II pneumocytes in the human lung. J Infect Dis. 2012:206(11):1685-94. doi: 10.1093/infdis/jis455.
30. 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. doi: 10.1001/jama.2020.1585.
31. Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020;9(1):727-32. doi: 10.1080/22221751.2020.1746199.
32. Wan SX, Yi QJ, Fan SB, Lv J, Zhang X, Guo L, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized
patients with 2019 novel coronavirus pneumonia (NCP). medRxiv. 2020. doi:https://doi.org/10.1101/2020.02.10.20021832.
33. Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, Wang J, et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013;48(6):742-8. doi: 10.1165/rcmb.2012-0339OC.
34. Mason RJ. Pathogenesis of COVID-19 from a cell biologic perspective. Eur Respir J. 2020;55(4). doi: 10.1183/13993003.00607-2020.
35. Kumar PA, Hu Y, Yamamoto Y, Hoe NB, Wei TS, Mu D, et al. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell. 2011:147(3):525-38. doi: 10.1016/j.cell.2011.10.001.
36. Yee M, Domm W, Gelein R, Bentley KL, Kottmann RM, Sime PJ, et al. Alternative Progenitor Lineages Regenerate the Adult Lung Depleted of Alveolar Epithelial Type 2 Cells. Am J Respir Cell Mol Biol. 2017:56(4):453-64. doi: 10.1165/rcmb.2016-0150OC.
37. Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007:170(4):1136-47. doi: 10.2353/ajpath.2007.061088.
38. 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.
39. Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4). doi: 10.3390/v12040372.
40. Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003;13(6):387-98. doi: 10.1002/rmv.405.
41. Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A. 2004:101(44):15748-53. doi: 10.1073/pnas.0403812101.
Submitted date:
04/29/2020
Reviewed date:
05/10/2020
Accepted date:
05/12/2020
Publication date:
05/13/2020