| Title: |
Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription |
| Authors: |
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. |
| Contributors: |
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. |
| Publisher Information: |
MDPI |
| Publication Year: |
2022 |
| Collection: |
Padua Research Archive (IRIS - Università degli Studi di Padova) |
| Subject Terms: |
Autopsy; Complement; COVID-19; Inflammation; SARS-CoV-2; Transcriptomic profiling |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35326463; info:eu-repo/semantics/altIdentifier/wos/WOS:000775839300001; volume:11; issue:6; firstpage:1011; journal:CELLS; https://hdl.handle.net/11577/3439355 |
| DOI: |
10.3390/cells11061011 |
| Availability: |
https://hdl.handle.net/11577/3439355; https://doi.org/10.3390/cells11061011 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.AD717060 |
| Database: |
BASE |