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| Immunostaining of SARS-CoV-2 in pulmonary tissues |
#15,280
As an EMT - nearly a half a century ago - I became pretty good friends with a county medical examiner, who maintained that:
An internist knows everything about nothing.While a wry, and somewhat biased observation, autopsies and post-mortem tissue examinations can tell us a great deal about the underlying pathogenesis of diseases. Something that is particularly important when an emerging virus like COVID-19 suddenly appears.
A surgeon knows nothing about everything.
And a pathologist knows everything about everything, just one day too late.
Yesterday the CDC's EID Journal published a lengthy, detailed, and highly technical review of the clinicopathologic, immunohistochemical, and electron microscopic findings from 8 fatal lab-confirmed cases of SARS-CoV-2 in the United States, 7 of which died in LTCFs.Unlike in other reports we've seen, these 8 cases did not appear to have significant extrapulmonary involvement. This, however, is a very small sampling. This study will be tough sledding for those without a medical background - and is too detailed for me to do it justice in this blog - so I'll simply post the link and a couple of excerpts and recommend you read it in its entirety.
Volume 26, Number 9—September 2020
Synopsis
Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States
Roosecelis B. Martines1, Jana M. Ritter1, Eduard Matkovic, Joy Gary, Brigid C. Bollweg, Hannah Bullock, Cynthia S. Goldsmith, Luciana Silva-Flannery, Josilene N. Seixas, Sarah Reagan-Steiner, Timothy Uyeki, Amy Denison, Julu Bhatnagar, Wun-Ju Shieh, Sherif R. Zaki, and COVID-19 Pathology Working Group
Abstract
An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures.
We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities.
In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.
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Study Patients and Data Collection
As part of the public health response to COVID-19, the CDC Infectious Diseases Pathology Branch (Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases) was consulted on autopsies of 8 patients with laboratory evidence of SARS-CoV-2 by reverse transcription PCR (RT-PCR) on respiratory swab specimens collected either before or after death.
We reviewed available medical records and preliminary autopsy reports for information regarding demographics, symptom history, underlying conditions, infectious disease testing, imaging study findings, treatment and advanced supportive care received, and date of death. This investigation was reviewed in accordance with CDC’s human subjects review procedures and was determined to not meet the definition of research.
Discussion
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This report describes the specific cellular and extracellular localization of SARS-CoV-2 in respiratory tissues, without any IHC evidence of the virus in other tissues. Although detection of SARS-CoV-2 RNA in blood or serum has been reported (34,41), we did not find evidence of systemic virus dissemination in these case-patients. Our findings highlight the importance of underlying conditions and pulmonary co-infections in COVID-19; these factors may potentially delay or confound diagnosis and contribute to adverse outcomes.
A limitation of this study is that 7 of 8 cases were from a single skilled nursing facility; findings may therefore not be representative of community-acquired SARS-CoV-2 infections. However, nosocomial transmission of viruses often parallels community outbreaks, and understanding disease transmission in healthcare settings is crucial (25,45). None of these case-patients had diagnoses of acute cardiac injury, myocarditis, or cardiomyopathy, so understanding the pathogenesis of cardiac injury with SARS-CoV-2 infection requires additional investigations in fatal cases with evidence of cardiac injury.
No clinical or histopathologic features are specific to SARS-CoV-2 infection. Demonstrating SARS-CoV-2 directly in lung tissue, when taken in context with any other pathology present, is critical to assessing its contribution to mortality.
Herein, we establish the utility of IHC as a diagnostic modality for SARS-CoV-2 in FFPE tissues by localizing viral antigens in respiratory tissues from RT-PCR confirmed cases. This diagnostic method is particularly valuable for FFPE specimens from cases in which antemortem or postmortem respiratory swab testing for SARS-CoV-2 was not performed. We also demonstrate virus identification in tissues by EM using various tissue sources (formalin-fixed wet tissue, FFPE blocks, and stained slides).
Identification of SARS-CoV-2 cellular tropisms in the respiratory tract represents a crucial step forward in understanding the pathogenesis of SARS-CoV-2 infection and provides some insights relevant to the development of targeted therapeutic and preventive measures to combat COVID-19.
Dr. Martines is a pathologist with the Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, Georgia, USA. Her primary research interest is in the pathology and pathogenesis of emerging infectious diseases, with particular interest in viral hemorrhagic fevers. Dr. Ritter is a pathologist with the Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta. Her primary research interest is the development of animal models for zoonotic and human infectious diseases.
