Two distinct immunopathological profiles in autopsy lungs of COVID-19
Open accessPublished version of a preprint
Abstract
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 ( n = 34 tissues from 16 patients) and normal lung tissues ( n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISG high ) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISG low ), low viral loads and abundant infiltrating activated CD8 + T cells and macrophages. ISG high patients die significantly earlier after hospitalization than ISG low patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
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Patients with COVID-19 with higher viral loads tended to have a shorter symptom onset-to-death time.
“Principal component analysis of these transcripts showed that, in general, patients with COVID-19 with higher viral loads tended to have a shorter SOTD (fig. S7), consistent with a previous report (35).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [35]
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References 51 · Cited by 246
Research works printed but not linked: 2
- [47]Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2016).
- [50]Horikoshi, M. & Tang, Y. ggfortify: Data visualization tools for statistical analysis results. v0. 1.0. http://CRAN.R-project.org/package=ggfortify.Rpackageversion0.4 1, 28 (2018).
- Authors
- Nienhold, R., Ciani, Y., Koelzer, V. H., Tzankov, A., Haslbauer, J. D., Menter, T., Schwab, N., Henkel, M., Frank, A., Zsikla, V., Willi, N., Kempf, W., Hoyler, T., Barbareschi, M., Moch, H., Tolnay, M., Cathomas, G., Demichelis, F., Junt, T., & Mertz, K. D.
- Affiliations
- Kantonsspital Baselland (CH)
- University of Trento (IT)
- University of Oxford (GB)
- University Hospital of Basel (CH)
- Novartis Institutes for BioMedical Research (CH)
- Ospedale Santa Chiara (IT)
- University Hospital Zurich (CH)
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Mertz, Kirsten D.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-10-08
- Volume
- 11
- Issue
- 1
- Pages
- 5086-5086
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7546638
- OpenAlex
- W3092519469
- Cited by
- 246
- References
- 51
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 18 · 2023: 38 · 2022: 62 · 2021: 98 · 2020: 11
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Iris (University of Trento) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Keywords
- COVID-19 pandemic, SARS-CoV-2, lung immunopathology, interferon-stimulated genes, cytokines, viral load, CD8+ T cells, macrophages, lung injury, post-mortem lung tissue, transcriptomics, disease progression, mortality, biomarkers
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Aged, Aged, 80 and over, Female, Humans, Interferons, Lung, Macrophages, Male, Middle Aged, Pneumonia, Viral, Cytokines, Coronavirus Infections, CD8-Positive T-Lymphocytes, Viral Load, Gene Expression Profiling, Pandemics
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