Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19
Authors: Teluguakula Narasaraju
Journal: Annals of Internal Medicine (2020)

Letters18 August 2020Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19FREETeluguakula Narasaraju, PhDTeluguakula Narasaraju, PhDCenter for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma (T.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0894 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Zhang and colleagues (1) examined histopathologic characteristics and immunostaining analysis in lung biopsy samples from a patient with coronavirus disease 2019 (COVID-19). These findings are critical, because they show the distribution of COVID-19 in infected lungs and early pathologic changes.I would like to mention 2 important aspects in these analyses. Panel A-1 in Figure 2 identified diffuse alveolar damage with necrotic epithelium and epithelial denudation. In addition to these lesions, I noticed substantial accumulation of neutrophil extracellular traps (NETs) in this histologic image. The NETs appear as elongated nuclear staining that presents as single cell in origin or forms as bundles in this biopsy section. Further, NETs are prominently seen in both airways and alveoli in this section. We previously observed similar pathologic lesions in mice infected with lethal influenza, as described in Figures 2 and 4 of our article (2). The presence of NETs in these tissue samples can be confirmed by immunostaining analysis using antibodies against histones, myeloperoxidase, or neutrophil elastase (2). I believe this factor is critical, because many clinical reports from patients with COVID-19 have identified neutrophilia as a prominent laboratory finding in all nonsurvivors compared with those who have recovered from this condition (3). A large increase in blood interleukin-8 levels also was found, suggesting the possibility of a massive neutrophil influx and activation in infected lungs (3).Another distinct pathologic finding from Zhang and colleagues' evaluation is the absence of hemorrhagic exudative lesions as described in lung autopsy analyses that were reported earlier (4). The absence of these lesions raises the question of whether the hemorrhagic and exudative vascular pathology could be an aftermath effect of early alveolar epithelial injury mediated by excessive neutrophils and NET-related toxic components. We similarly observed 2 distinct phages in mice infected with fatal influenza (5). At early stages of infection, we observed necrotic epithelia, epithelial denudation, and massive neutrophil influx/NETs. However, at late stages of infection, we observed a clear hemorrhagic exudative pathology with a decreased presence of immune cells, similar to pathologic lesions observed in lung autopsy studies in patients with COVID-19. Analysis of bronchoalveolar lavage fluids or temporal lung biopsy specimens will determine whether immunopathology plays a major role in pathologic manifestations of acute respiratory distress syndrome in patients with COVID-19.Immunostaining analysis furthermore shows wide distribution of the virus in different epithelial cells and immune cells (such as macrophages), as seen in the bright field images. Identifying different cell types using cell-specific markers would help us understand the possible target cells for the virus. Doing so would help other researchers quickly set up in vitro lung epithelial cell culture models to test the efficacy of the antiviral activity of various novel drugs.References1. Zhang H, Zhou P, Wei Y, et al. Histopathologic changes and SARS-CoV-2 immunostaining in the lung of a patient with COVID-19 [Letter]. Ann Intern Med. 2020;172:629-632. [PMID: 32163542]. doi:10.7326/M20-0533 LinkGoogle Scholar2. Narasaraju T, Yang E, Samy RP, et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011;179:199-210. [PMID: 21703402] doi:10.1016/j.ajpath.2011.03.013 CrossrefMedlineGoogle Scholar3. Gong J, Dong H, Xia SQ, et al. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19 pneumonia. medRxiv. Preprint posted online 27 February 2020. doi:10.1101/2020.02.25.20025643 Google Scholar4. Luo W, Yu H, Gou J, et al. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19). Preprints. Preprint posted online 27 February 2020. Google Scholar5. Ashar HK, Mueller NC, Rudd JM, et al. The role of extracellular histones in influenza virus pathogenesis. Am J Pathol. 2018;188:135-148. [PMID: 29107075] doi:10.1016/j.ajpath.2017.09.014 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Teluguakula Narasaraju, PhDAffiliations: Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma (T.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0894. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHistopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19 Huilan Zhang , Peng Zhou , Yanqiu Wei , Huihui Yue , Yi Wang , Ming Hu , Shu Zhang , Tanze Cao , Chengqing Yang , Ming Li , Guangyun Guo , Xianxiang Chen , Ying Chen , Mei Lei , Huiguo Liu , Jianping Zhao , Peng Peng , Cong-Yi Wang , and Ronghui Du Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19 Huilan Zhang , Cong-Yi Wang , Peng Zhou , Huihui Yue , and Ronghui Du Metrics Cited byTherapeutic approaches for SARS-CoV-2 infectionImaging Evaluation of Pulmonary and Non-Ischaemic Cardiovascular Manifestations of COVID-19Implications of microscale lung damage for COVID-19 pulmonary ventilation dynamics: A narrative reviewSARS-CoV-2 Infection of Airway Epithelial Cells 18 August 2020Volume 173, Issue 4 Page: 323-324 Keywords Biopsy COVID-19 Epithelial cells Histones Immunohistochemistry Immunopathology Lesions Lungs Neutrophils Research laboratories ePublished: 18 August 2020 Issue Published: 18 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. 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