Two distinct immunopathological profiles in autopsy lungs of COVID-19.

Ronny Nienhold, Yari Ciani, Viktor H Koelzer, Alexandar Tzankov, Jasmin D Haslbauer, Thomas Menter, Nathalie Schwab, Maurice Henkel, Angela Frank, Veronika Zsikla, Niels Willi, Werner Kempf, Thomas Hoyler, Mattia Barbareschi, Holger Moch, Markus Tolnay, Gieri Cathomas, Francesca Demichelis, Tobias Junt, Kirsten D Mertz
Author Information
  1. Ronny Nienhold: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  2. Yari Ciani: Laboratory of Computational and Functional Oncology, Department for Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy. ORCID
  3. Viktor H Koelzer: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland. ORCID
  4. Alexandar Tzankov: Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. ORCID
  5. Jasmin D Haslbauer: Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  6. Thomas Menter: Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. ORCID
  7. Nathalie Schwab: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  8. Maurice Henkel: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland. ORCID
  9. Angela Frank: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  10. Veronika Zsikla: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  11. Niels Willi: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  12. Werner Kempf: Kempf und Pfaltz Histologische Diagnostik, Zurich, Switzerland.
  13. Thomas Hoyler: Novartis Institutes for BioMedical Research (NIBR), Basel, Switzerland.
  14. Mattia Barbareschi: Anatomia ed Istologia Patologica, Ospedale S. Chiara di Trento, Trento, Italy. ORCID
  15. Holger Moch: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
  16. Markus Tolnay: Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  17. Gieri Cathomas: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  18. Francesca Demichelis: Laboratory of Computational and Functional Oncology, Department for Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy. ORCID
  19. Tobias Junt: Novartis Institutes for BioMedical Research (NIBR), Basel, Switzerland.
  20. Kirsten D Mertz: Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland. kirsten.mertz@ksbl.ch. ORCID

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) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISG), low viral loads and abundant infiltrating activated CD8 T cells and macrophages. ISG patients die significantly earlier after hospitalization than ISG 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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MeSH Term

Aged
Aged, 80 and over
Betacoronavirus
CD8-Positive T-Lymphocytes
COVID-19
Coronavirus Infections
Cytokines
Female
Gene Expression Profiling
Humans
Interferons
Lung
Macrophages
Male
Middle Aged
Pandemics
Pneumonia, Viral
SARS-CoV-2
Viral Load

Chemicals

Cytokines
Interferons