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

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&#39;Byrne, K

Author(s): 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;
Details: Publication Year 2022-06,Volume 59,Issue #6,Page 2101881
Journal Title: European Respiratory Journal
Abstract: 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.
Publisher: ERS
Keywords: COVID-19/genetics; Humans; Influenza A Virus, H1N1 Subtype; *nfluenza, Human/genetics; Interferon Type I/metabolism; Lung/pathology; SARS-CoV-2
Research Division(s): Bioinformatics
PubMed ID: 34675048
Publisher's Version: https://doi.org/10.1183/13993003.01881-2021
Open Access at Publisher's Site: https://doi.org/10.1183/13993003.01881-2021
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: 2101881.full.pdf - (2.09MB, application/pdf)

Creation Date: 2023-02-24 09:21:06

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