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Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures #MMPMID34675048
Kulasinghe A; Tan CW; Ribeiro Dos Santos Miggiolaro AF; Monkman J; SadeghiRad H; Bhuva DD; Motta Junior JDS; Busatta Vaz de Paula C; Nagashima S; Baena CP; Souza-Fonseca-Guimaraes P; de Noronha L; McCulloch T; Rossi GR; Cooper C; Tang B; Short KR; Davis MJ; Souza-Fonseca-Guimaraes F; Belz GT; O'Byrne K
Eur Respir J 2022[Jun]; 59 (6): ä PMID34675048show ga
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies. METHODS: Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients. RESULTS: Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza. CONCLUSION: Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.