학술논문
Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription.
Document Type
Article
Author
Fassan, Matteo; Collesei, Antonio; Angerilli, Valentina; Sbaraglia, Marta; Fortarezza, Francesco; Pezzuto, Federica; De Gaspari, Monica; Businello, Gianluca; Moni, Margherita; Rizzo, Stefania; Traverso, Giulia; Colosso, Veronica; Taschin, Elisa; Lunardi, Francesca; Valls, Aida Freire; Schiavi, Francesca; Basso, Cristina; Calabrese, Fiorella; Dei Tos, Angelo Paolo
Source
Subject
*AUTOPSY
*TYPE I interferons
*GENE expression profiling
*COVID-19
*GENETIC overexpression
*PROTEIN C
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Language
ISSN
2073-4409
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. [ABSTRACT FROM AUTHOR]