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Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies.
Histopathology. 2020 Jul 02 [Online ahead of print]H

Abstract

INTRODUCTION

We describe postmortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalization.

METHODS

Histopathologic findings in postmortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next generation sequencing (NGS) were performed to detect virus.

RESULTS

Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organizing phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium and large caliber vessels, platelet microthrombi detected by CD61 IHC, and fibrin microthrombi.

CONCLUSIONS

Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute but not in the organizing phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organizing phase, the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Laboratory Medicine and Pathology, University of Vermont Medical Center, Burlington, VT, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Pathology and Cell Biology, Columbia University, Columbia, USA.Infectious Disease, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Weill Cornell Medical College, New York, NY, USA.Department of Laboratory Medicine and Pathology, University of Vermont Medical Center, Burlington, VT, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Department of Pathology, New York University Long Island School of Medicine, Mineola, NY, USA.Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.Department of Pathology, New York University Long Island School of Medicine, Mineola, NY, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32614086

Citation

Sauter, Jennifer L., et al. "Insights Into Pathogenesis of Fatal COVID-19 Pneumonia From Histopathology With Immunohistochemical and Viral RNA Studies." Histopathology, 2020.
Sauter JL, Baine MK, Butnor KJ, et al. Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies. Histopathology. 2020.
Sauter, J. L., Baine, M. K., Butnor, K. J., Buonocore, D. J., Chang, J. C., Jungbluth, A. A., Szabolcs, M. J., Morjaria, S., Mount, S. L., Rekhtman, N., Selbs, E., Sheng, Z. M., Xiao, Y., Kleiner, D. E., Pittaluga, S., Taubenberger, J. K., Rapkiewicz, A. V., & Travis, W. D. (2020). Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies. Histopathology. https://doi.org/10.1111/his.14201
Sauter JL, et al. Insights Into Pathogenesis of Fatal COVID-19 Pneumonia From Histopathology With Immunohistochemical and Viral RNA Studies. Histopathology. 2020 Jul 2; PubMed PMID: 32614086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies. AU - Sauter,Jennifer L, AU - Baine,Marina K, AU - Butnor,Kelly J, AU - Buonocore,Darren J, AU - Chang,Jason C, AU - Jungbluth,Achim A, AU - Szabolcs,Matthias J, AU - Morjaria,Sejal, AU - Mount,Sharon L, AU - Rekhtman,Natasha, AU - Selbs,Elena, AU - Sheng,Zong-Mei, AU - Xiao,Yongli, AU - Kleiner,David E, AU - Pittaluga,Stefania, AU - Taubenberger,Jeffery K, AU - Rapkiewicz,Amy V, AU - Travis,William D, Y1 - 2020/07/02/ PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - COVID-19 KW - SARS-CoV-2 KW - diffuse alveolar damage KW - immunohistochemistry KW - lung histopathology KW - next generation sequencing KW - thrombi KW - viral pneumonia JF - Histopathology JO - Histopathology N2 - INTRODUCTION: We describe postmortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalization. METHODS: Histopathologic findings in postmortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next generation sequencing (NGS) were performed to detect virus. RESULTS: Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organizing phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium and large caliber vessels, platelet microthrombi detected by CD61 IHC, and fibrin microthrombi. CONCLUSIONS: Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute but not in the organizing phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organizing phase, the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention. SN - 1365-2559 UR - https://www.unboundmedicine.com/medline/citation/32614086/Insights_into_pathogenesis_of_fatal_COVID_19_pneumonia_from_histopathology_with_immunohistochemical_and_viral_RNA_studies_ L2 - https://doi.org/10.1111/his.14201 DB - PRIME DP - Unbound Medicine ER -
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