Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures

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dc.contributor.authorKulasinghe, A.
dc.contributor.authorTan, C.W.
dc.contributor.authorRibeiro Dos Santos Miggiolaro, A.F.
dc.contributor.authorMonkman, J.
dc.contributor.authorSadeghiRad, H.
dc.contributor.authorBhuva, D.D.
dc.contributor.authorMotta Junior, J.D.S.
dc.contributor.authorBusatta Vaz de Paula, C.
dc.contributor.authorNagashima, S.
dc.contributor.authorBaena, C.P.
dc.contributor.authorSouza-Fonseca-Guimaraes, P.
dc.contributor.authorde Noronha, L.
dc.contributor.authorMcCulloch, T.
dc.contributor.authorRossi, G.R.
dc.contributor.authorCooper, C.
dc.contributor.authorTang, B.
dc.contributor.authorShort, K.R.
dc.contributor.authorDavis, M.J.
dc.contributor.authorSouza-Fonseca-Guimaraes, F.
dc.contributor.authorBelz, G.T.
dc.contributor.authoret al.
dc.date.issued2022
dc.description.abstractBACKGROUND: 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.
dc.description.statementofresponsibilityArutha Kulasinghe, Chin Wee Tan, Anna Flavia Ribeiro dos Santos Miggiolaro, James Monkman, Habib SadeghiRad, Dharmesh D. Bhuva, Jarbas da Silva Motta Junior, Caroline Busatta Vaz de Paula, Seigo Nagashima, Cristina Pellegrino Baena, Paulo Souza-Fonseca-Guimaraes, Lucia de Noronha, Timothy McCulloch, Gustavo Rodrigues Rossi, Caroline Cooper, Benjamin Tang, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca-Guimaraes, Gabrielle T. Belz, and Ken O, Byrne
dc.identifier.citationEuropean Respiratory Journal, 2022; 59(6):1-19
dc.identifier.doi10.1183/13993003.01881-2021
dc.identifier.issn0903-1936
dc.identifier.issn1399-3003
dc.identifier.orcidBhuva, D.D. [0000-0002-6398-9157]
dc.identifier.orcidDavis, M.J. [0000-0003-4864-7033]
dc.identifier.urihttps://hdl.handle.net/2440/135620
dc.language.isoen
dc.publisherEuropean Respiratory Society (ERS)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1157741
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1135898
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140406
dc.rights©The authors 2022. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org
dc.source.urihttps://doi.org/10.1183/13993003.01881-2021
dc.subjectCOVID-19
dc.subjectHumans
dc.subjectInfluenza A Virus, H1N1 Subtype
dc.subjectInfluenza, Human
dc.subjectInterferon Type I
dc.subjectLung
dc.subjectSARS-CoV-2
dc.subject.meshLung
dc.subject.meshHumans
dc.subject.meshInterferon Type I
dc.subject.meshInfluenza, Human
dc.subject.meshInfluenza A Virus, H1N1 Subtype
dc.subject.meshCOVID-19
dc.subject.meshSARS-CoV-2
dc.titleProfiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
dc.typeJournal article
pubs.publication-statusPublished

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