Lung pathology of fatal severe acute respiratory syndrome
Open accessAbstract
Background Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. Methods Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. Findings All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. Interpretation SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease.
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The cytokine storm induced by excessive T-cell responses has been shown to accentuate the pathogenesis of COVID-19.
“The “cytokine storm” induced by excessive T-cell responses have been actually shown to accentuate the pathogenesis of COVID19 (18, 19).”
From Development of an inactivated vaccine candidate for SARS-CoV-2 (2020) · cites this paper as [18]
The Discussion (page unavailable) suggests that cytokines released by stimulated macrophages contribute to the pathogenesis of SARS. It does not show that excessive T-cell responses induce a cytokine storm or that this mechanism accentuates COVID-19 pathogenesis; it also presents the SARS mechanism as a suggestion rather than an established finding. (LLM, conf=0.88)
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- Authors
- Nicholls, J. M., Poon, L. L., Lee, K. C., Ng, W. F., Lai, S. T., Leung, C. Y., Chu, C. M., Hui, P. K., Mak, K. L., Lim, W., Yan, K. W., Chan, K. H., Tsang, N. C., Guan, Y., Yuen, K. Y., & Malik Peiris, J.
- Affiliations
- University of Hong Kong (HK)
- Yan Chai Hospital (HK)
- United Christian Hospital (CN)
- Kwong Wah Hospital (CN)
- Queen Elizabeth Hospital (CN)
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 361
- Issue
- 9371
- Pages
- 1773-1778
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC7112492
- OpenAlex
- W1971054351
- Cited by
- 1,076
- References
- 0
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 18 · 2023: 40 · 2022: 73 · 2021: 139 · 2020: 280 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 11 · 2015: 17 · 2014: 15 · 2013: 12 · 2012: 14
- FWCI
- 56.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Wellcome Trust
- University of Hong Kong
- U.S. Public Health Service (A195357)
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- SARS, SARS-associated coronavirus, lung pathology, diffuse alveolar damage, hemophagocytosis, alveolar macrophages, squamous metaplasia, human metapneumovirus, cytokine imbalance
- MeSH terms
- Adult, Biopsy, Bronchi, Cell Nucleus, Female, Humans, Lung, Male, Metaplasia, Middle Aged, Organ Size, Giant Cells, Fatal Outcome, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus
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