Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19
Authors: Huilan Zhang, Cong-Yi Wang, Peng Zhou, Huihui Yue, Ronghui Du
Journal: Annals of Internal Medicine (2020)

Letters18 August 2020Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19FREEHuilan Zhang, PhD, Cong-Yi Wang, PhD, Peng Zhou, PhD, Huihui Yue, MD, and Ronghui Du, MDHuilan Zhang, PhDCenter for Biomedical Research, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.Z., C.W., H.Y.)Search for more papers by this author, Cong-Yi Wang, PhDCenter for Biomedical Research, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.Z., C.W., H.Y.)Search for more papers by this author, Peng Zhou, PhDCAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China (P.Z.)Search for more papers by this author, Huihui Yue, MDCenter for Biomedical Research, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (H.Z., C.W., H.Y.)Search for more papers by this author, and Ronghui Du, MDWuhan Pulmonary Hospital, Wuhan, China (R.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0895 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We believe that the resolution of the issues noted by Dr. Narasaraju would provide valuable information to help understand the pathogenesis and pathologic mechanisms underlying COVID-19. Here, we respond to the 3 points that he raised.First, Dr. Narasaraju noticed the gathering of neutrophils evidenced by the elongated nuclear staining in panel A-1 of Figure 2 of our case report. To address this concern, our team further examined lung sections for neutrophils (MPO+) and macrophages (CD68+) by immunostaining. We found that macrophages were the predominant infiltrating cells; neutrophils accounted for merely a small proportion, which is consistent with previous studies (1, 2). Given that neutrophil extracellular NETs—which are critical for the bactericidal function of neutrophils—are a specialized molecular structure formed by dying neutrophils, it is therefore plausible that massive neutrophil infiltration would be obvious upon the occurrence of severe secondary bacterial infection.Second, we do not exclude the possibility that patients with COVID-19 could exhibit lung hemorrhagic changes. However, this was not the case in our patient, which could be related to the disease course and disease severity of patients with COVID-19. More autopsy evidence and clinical information are therefore needed to confirm the correlation between hemorrhagic pathologic changes and COVID-19, such as whether patients received extracorporeal membrane oxygenation before death or had such comorbidities as severe coagulation dysfunction.Finally, we co-stained severe acute respiratory syndrome coronavirus 2 with CD3+ (T-cell marker), CD68+ (macrophage marker), and MPO+ (neutrophil marker) by immunofluorescence. The results showed that it did involve several immune cells, including T cells, macrophages, and a few neutrophils.We hope that our clarifications have shed more light on the mechanisms and pathologic processes of COVID-19.References1. 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 Scholar2. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420-422. [PMID: 32085846] doi:10.1016/S2213-2600(20)30076-X CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Huilan Zhang, PhD; Cong-Yi Wang, PhD; Peng Zhou, PhD; Huihui Yue, MD; Ronghui Du, MDAffiliations: 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., C.W., H.Y.)CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China (P.Z.)Wuhan Pulmonary Hospital, Wuhan, China (R.D.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0533. 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