101. Spatial profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
- Author
-
Kulasinghe, Arutha, Tan, Chin Wee, Miggiolaro, Anna Flavia Ribeiro dos Santos, Monkman, James, Bhuva, Dharmesh, Junior, Jarbas da Silva Motta, Paula, Caroline Busatta Vaz de, Nagashima, Seigo, Baena, Cristina Pellegrino, Souza-Fonseca-Guimaraes, Paulo, Noronha, Lucia de, McCulloch, Timothy, Rossi, Gustavo Rodrigues, Cooper, Caroline, Tang, Benjamin, Short, Kirsty R., Davis, Melissa J, Souza-Fonseca-Guimaraes, Fernando, Belz, Gabrielle T., O’Byrne, Ken, Kulasinghe, Arutha, Tan, Chin Wee, Miggiolaro, Anna Flavia Ribeiro dos Santos, Monkman, James, Bhuva, Dharmesh, Junior, Jarbas da Silva Motta, Paula, Caroline Busatta Vaz de, Nagashima, Seigo, Baena, Cristina Pellegrino, Souza-Fonseca-Guimaraes, Paulo, Noronha, Lucia de, McCulloch, Timothy, Rossi, Gustavo Rodrigues, Cooper, Caroline, Tang, Benjamin, Short, Kirsty R., Davis, Melissa J, Souza-Fonseca-Guimaraes, Fernando, Belz, Gabrielle T., and O’Byrne, Ken
- 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). Robust blood biomarkers that reflect tissue damage are urgently needed to better stratify and triage infected patients. Here, we use spatial transcriptomics to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19 (10 patients), pandemic H1N1 (pH1N1) influenza (5) and uninfected control patients (4). 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 with few areas of high viral load and these were largely only associated with an increased type I interferon response. A very limited number of genes were differentially expressed between the lungs of influenza and COVID-19 patients. Specific interferon-associated genes (including IFI27) were identified as candidate novel biomarkers for COVID-19 differentiating this COVID-19 from 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.
- Published
- 2020