Spatial Profiling of Lung SARS-CoV-2 and Influenza Virus Infection Dissects Virus-Specific Host Responses and Gene Signatures

Kulasinghe, A.; Tan, C. W.; Miggiolaro, A. F. R. d. S.; Monkman, J.; Bhuva, D.; Junior, J. d. S. M.; de Paula, C. B. V.; Nagashima, S.; Baena, C. P.; Guimaraes, P. S.-F.; Noronha, L.; McCulloch, T.; Rossi, G. R.; Cooper, C.; Tang, B.; Short, K.; Davis, M. J.; Guimaraes, F. S.-F.; Belz, G. T.; O'Byrne, K.

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.