tetano
Editor, Senior Moderator
Eur Respir J
. 2021 Oct 21;2101881.
doi: 10.1183/13993003.01881-2021. Online ahead of print.
Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
Arutha Kulasinghe[SUP] 1 2 3 4 [/SUP], Chin Wee Tan[SUP] 5 6 4 [/SUP], Anna Flavia Ribeiro Dos Santos Miggiolaro[SUP] 7 4 [/SUP], James Monkman[SUP] 8 2 [/SUP], Habib SadeghiRad[SUP] 8 2 [/SUP], Dharmesh D Bhuva[SUP] 5 6 [/SUP], Jarbas da Silva Motta Junior[SUP] 7 [/SUP], Caroline Busatta Vaz de Paula[SUP] 7 [/SUP], Seigo Nagashima[SUP] 7 [/SUP], Cristina Pellegrino Baena[SUP] 9 [/SUP], Paulo Souza-Fonseca-Guimaraes[SUP] 6 [/SUP], Lucia de Noronha[SUP] 10 [/SUP], Timothy McCulloch[SUP] 2 3 [/SUP], Gustavo Rodrigues Rossi[SUP] 2 3 [/SUP], Caroline Cooper[SUP] 11 12 [/SUP], Benjamin Tang[SUP] 13 [/SUP], Kirsty R Short[SUP] 14 15 16 [/SUP], Melissa J Davis[SUP] 5 6 17 16 [/SUP], Fernando Souza-Fonseca-Guimaraes[SUP] 2 3 16 [/SUP], Gabrielle T Belz[SUP] 2 3 5 15 16 [/SUP], Ken O'Byrne[SUP] 8 2 16 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that 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. Here, we use targeted transcriptomics of FFPE 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. 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. 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.
. 2021 Oct 21;2101881.
doi: 10.1183/13993003.01881-2021. Online ahead of print.
Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
Arutha Kulasinghe[SUP] 1 2 3 4 [/SUP], Chin Wee Tan[SUP] 5 6 4 [/SUP], Anna Flavia Ribeiro Dos Santos Miggiolaro[SUP] 7 4 [/SUP], James Monkman[SUP] 8 2 [/SUP], Habib SadeghiRad[SUP] 8 2 [/SUP], Dharmesh D Bhuva[SUP] 5 6 [/SUP], Jarbas da Silva Motta Junior[SUP] 7 [/SUP], Caroline Busatta Vaz de Paula[SUP] 7 [/SUP], Seigo Nagashima[SUP] 7 [/SUP], Cristina Pellegrino Baena[SUP] 9 [/SUP], Paulo Souza-Fonseca-Guimaraes[SUP] 6 [/SUP], Lucia de Noronha[SUP] 10 [/SUP], Timothy McCulloch[SUP] 2 3 [/SUP], Gustavo Rodrigues Rossi[SUP] 2 3 [/SUP], Caroline Cooper[SUP] 11 12 [/SUP], Benjamin Tang[SUP] 13 [/SUP], Kirsty R Short[SUP] 14 15 16 [/SUP], Melissa J Davis[SUP] 5 6 17 16 [/SUP], Fernando Souza-Fonseca-Guimaraes[SUP] 2 3 16 [/SUP], Gabrielle T Belz[SUP] 2 3 5 15 16 [/SUP], Ken O'Byrne[SUP] 8 2 16 [/SUP]
Affiliations
- PMID: 34675048
- DOI: 10.1183/13993003.01881-2021
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that 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. Here, we use targeted transcriptomics of FFPE 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. 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. 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.