Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19FREE
Background: Although many studies have demonstrated the epidemiologic characteristics of SARS-CoV-2 disease (COVID-19), details of pathologic changes in the lung are still lacking.
Objective: To describe the histopathologic changes in the lung of a patient with COVID-19.
Case Report: A 72-year-old man with a history of diabetes and hypertension presented with fever and cough. His throat and pharyngeal swabs were positive for SARS-CoV-2 by day 6 after the initial symptoms. Rapidly progressive respiratory failure required endotracheal intubation and mechanical ventilation 1 week after presentation.
Lung tissue was obtained by transthoracic 14-gauge needle biopsy from the left upper anterior segment (Figure 1, A, arrow), left upper lingular segment (Figure 1, B, arrow), and left lower lobe (Figure 1, C, arrow), coinciding with ground-glass opacities on chest computed tomography (CT). Two throat swab samples were collected from the tonsils and posterior pharyngeal wall.
Biopsy lung sections were analyzed with hematoxylin–eosin staining, and immunostaining for SARS-CoV-2 was conducted as reported elsewhere (1). Throat swabs were assessed for SARS-CoV-2 by using real-time reverse transcriptase polymerase chain reaction assays (2).
The CT scans revealed patchy bilateral ground glass–like opacifications (Figure 1, A to C, arrows). Despite antiviral therapies, respiratory and hemodynamic instability continued and the patient died 3 weeks after diagnosis. Permission for postmortem transthoracic needle biopsy, but not autopsy, was obtained from the patient's family.
Histopathologic examination of lung biopsy tissues revealed diffuse alveolar damage, organizing phase. Denuded alveolar lining cells (Figure 2, A-1, arrow 1), with reactive type II pneumocyte hyperplasia, were noted (Figure 2, A-1, arrow 2). Intra-alveolar fibrinous exudates were present (Figure 2, A-2, arrow 3), along with loose interstitial fibrosis and chronic inflammatory infiltrates (Figure 2, A-2, arrow 4). Intra-alveolar loose fibrous plugs of organizing pneumonia were noted (Figure 2, A-3, arrow 5), with presence of intra-alveolar organizing fibrin seen in most foci (Figure 2, A-4, arrow 6).
Immunostaining of lung sections with an antibody to the Rp3 NP protein of SARS-CoV-2 revealed prominent expression on alveolar epithelial cells (Figure 2, B, top panel), including damaged, desquamated cells within the alveolar space (Figure 2, B, bottom panel, green arrows). In contrast, viral protein expression was minimally detectable on blood vessels (Figure 2, B, dashed black line) or in the interstitial areas between alveoli (Figure 2, B, bottom panel, blue arrows). Immunostaining of Huh7 cells infected with SARS-CoV-2 and of lung sections from an HIV-positive patient who died of fungal infection served as positive and negative staining controls, respectively (Figure 2, C).
Discussion: The histopathologic changes seen on postmortem transthoracic needle biopsies from a patient with COVID-19 who had respiratory failure and radiographic bilateral ground-glass opacities are consistent with diffuse alveolar damage. Although such nonspecific findings may be seen in response to several conditions that result in respiratory failure, its demonstration in the setting of COVID-19 helps to inform the clinical course of disease.
Our study is limited by our inability to obtain larger tissue specimens. The present findings warrant further study with larger tissue samples, obtained by open or thoracoscopic lung biopsy, or autopsy, for example.
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Author, Article and Disclosure Information
Center for Biomedical Research, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.Z., Y.W., H.Y., Y.W., S.Z., H.L., J.Z., C.W.)
CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China (P.Z., Y.C.)
Wuhan Pulmonary Hospital, Wuhan, China (M.H., C.Y., M.L., G.G., X.C., P.P., R.D.)
Pulmonary Hospital, Wuhan, China (T.C.)
Institution of Tuberculosis for Prevention and Cure, Wuhan Pulmonary Hospital, Wuhan, China (M.L.)
Note: Authors indicated with an asterisk (Drs. H. Zhang, P. Zhou, Y. Wei, H. Yue, Y. Wang, and M. Hu) contributed equally to this article. Authors indicated with a dagger (Drs. M. Lei, H. Liu, J. Zhao, P. Peng, C-Y. Wang, and R. Du) served as co–senior authors.
Financial Support: By the National Natural Science Foundation of China (grants 81974456 and 91749207); the Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology (grant 5001540075); and the SARS-CoV-2 Pneumonia Emergency Technology Public Relations Project (grants 2020FCA009 and 2020FCA026).
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0533.
Correction: This article was corrected on 25 March 2020 to update author contributions for Drs. M. Lei, H. Liu, J. Zhao, P. Peng, C-Y. Wang, and R. Du.
This article was published at Annals.org on 12 March 2020.