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Article

Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription

by
Matteo Fassan
1,2,3,*,†,
Antonio Collesei
4,5,†,
Valentina Angerilli
1,
Marta Sbaraglia
1,2,
Francesco Fortarezza
2,
Federica Pezzuto
2,6,
Monica De Gaspari
6,
Gianluca Businello
1,
Margherita Moni
1,
Stefania Rizzo
6,7,
Giulia Traverso
1,
Veronica Colosso
4,
Elisa Taschin
4,
Francesca Lunardi
1,6,
Aida Freire Valls
8,
Francesca Schiavi
4,
Cristina Basso
6,7,‡,
Fiorella Calabrese
2,6,‡ and
Angelo Paolo Dei Tos
1,2,‡
1
Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy
2
Surgical Pathology Unit, Padua University Hospital, 35121 Padua, Italy
3
Veneto Institute of Oncology, IOV-IRCCS, 35128 Padua, Italy
4
Familial Cancer Clinics, Veneto Institute of Oncology, IOV-IRCCS, 35127 Padua, Italy
5
Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy
6
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy
7
Cardiovascular Pathology Unit, Padua University Hospital, 35121 Padua, Italy
8
NanoString Technologies, Inc., 530 Fairview Avenue N, Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work as first author.
‡
These authors contributed equally to this work as last author.
Cells 2022, 11(6), 1011; https://doi.org/10.3390/cells11061011
Submission received: 23 February 2022 / Revised: 11 March 2022 / Accepted: 14 March 2022 / Published: 16 March 2022
(This article belongs to the Collection Cellular Immunology and COVID-19)
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Abstract

The transcriptomic profiling of lung damage associated with SARS-CoV-2 infection may lead to the development of effective therapies to prevent COVID-19-related deaths. We selected a series of 21 autoptic lung samples, 14 of which had positive nasopharyngeal swabs for SARS-CoV-2 and a clinical diagnosis of COVID-19-related death; their pulmonary viral load was quantified with a specific probe for SARS-CoV-2. The remaining seven cases had no documented respiratory disease and were used as controls. RNA from formalin-fixed paraffin-embedded (FFPE) tissue samples was extracted to perform gene expression profiling by means of targeted (Nanostring) and comprehensive RNA-Seq. Two differential expression designs were carried out leading to relevant results in terms of deregulation. SARS-CoV-2 positive specimens presented a significant overexpression in genes of the type I interferon signaling pathway (IFIT1, OAS1, ISG15 and RSAD2), complement activation (C2 and CFB), macrophage polarization (PKM, SIGLEC1, CD163 and MS4A4A) and Cathepsin C (CTSC). CD163, Siglec-1 and Cathepsin C overexpression was validated by immunohistochemistry. SFTPC, the encoding gene for pulmonary-associated surfactant protein C, emerged as a key identifier of COVID-19 patients with high viral load. This study successfully recognized SARS-CoV-2 specific immune signatures in lung samples and highlighted new potential therapeutic targets. A better understanding of the immunopathogenic mechanisms of SARS-CoV-2 induced lung damage is required to develop effective individualized pharmacological strategies.
Keywords: SARS-CoV-2; COVID-19; autopsy; transcriptomic profiling; inflammation; complement SARS-CoV-2; COVID-19; autopsy; transcriptomic profiling; inflammation; complement

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MDPI and ACS Style

Fassan, M.; Collesei, A.; Angerilli, V.; Sbaraglia, M.; Fortarezza, F.; Pezzuto, F.; De Gaspari, M.; Businello, G.; Moni, M.; Rizzo, S.; et al. Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription. Cells 2022, 11, 1011. https://doi.org/10.3390/cells11061011

AMA Style

Fassan M, Collesei A, Angerilli V, Sbaraglia M, Fortarezza F, Pezzuto F, De Gaspari M, Businello G, Moni M, Rizzo S, et al. Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription. Cells. 2022; 11(6):1011. https://doi.org/10.3390/cells11061011

Chicago/Turabian Style

Fassan, Matteo, Antonio Collesei, Valentina Angerilli, Marta Sbaraglia, Francesco Fortarezza, Federica Pezzuto, Monica De Gaspari, Gianluca Businello, Margherita Moni, Stefania Rizzo, and et al. 2022. "Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription" Cells 11, no. 6: 1011. https://doi.org/10.3390/cells11061011

APA Style

Fassan, M., Collesei, A., Angerilli, V., Sbaraglia, M., Fortarezza, F., Pezzuto, F., De Gaspari, M., Businello, G., Moni, M., Rizzo, S., Traverso, G., Colosso, V., Taschin, E., Lunardi, F., Valls, A. F., Schiavi, F., Basso, C., Calabrese, F., & Dei Tos, A. P. (2022). Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription. Cells, 11(6), 1011. https://doi.org/10.3390/cells11061011

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