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

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

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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 Rockets 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 Multi-Tools 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.