Annals of Internal Medicine:
LETTERS |5 MAY 2020
Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19 FREE
Huilan Zhang, PhD *; Peng Zhou, PhD *; Yanqiu Wei, MD *; Huihui Yue, MD *; Yi Wang, PhD *; Ming Hu, MD *; Shu Zhang, PhD; Tanze Cao, MD; Chengqing Yang, MD; Ming Li, MD; Guangyun Guo, MD; Xianxiang Chen, MD; Ying Chen, MD; Mei Lei, MD †; Huiguo Liu, PhD †; Jianping Zhao, PhD †; Peng Peng, MD †; Cong-Yi Wang, PhD †; Ronghui Du, MD †
- FULL ARTICLE
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.
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.
,et alA pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature2020
,et alDetection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.Euro Surveill202025