Project description:We examined host gene expression across infection status, viral load, age, and sex among RNA-sequencing profiles of nasopharyngeal swabs from 430 individuals with SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong interferon-driven antiviral response and reduced transcription of ribosomal proteins. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load. B cells and neutrophils were higher in patients with lower viral load. Older individuals had reduced expression of chemokines CXCL9/10/11, their cognate receptor CXCR3, and CD8A and granzyme B. Males had reduced B and NK cell-specific transcripts and increased NFkB inhibitors. Our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.
Project description:We examined host gene expression in human airway epithelial cells following infection at 3 or 7 days post infection (DPI) with SARS-CoV-2
Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. We conducted a longitudinal study to investigate gene expression patterns during the acute SARS-CoV-2 illness. The cases included SARS-CoV-2 infected individuals with an extremely high viral load early in their illness matched to individuals who either had a low SARS-CoV-2 viral load early in their infection or were otherwise stable patients who tested negative for SARS-CoV-2 prior to their outpatient surgical or aerosol generating procedure. We detected hundreds of up-regulated genes that were highly correlated to the SARS-CoV-2 viral load. Many of these up-regulated genes were enriched in cellular pathways involved in the innate immune response, antiviral interferon and cytokine signaling, and cell death.
Project description:The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We visualized viral RNA by in situ hybridization and assessed the immune infiltrate using immunohistochemistry and total RNA sequencing on five COVID-19 positive patients. Patients with high levels of viral RNA showed hyaline membranes on histology, extensive pneumocyte loss, low T-cell numbers and were enriched for the interferon gene signature, while patients with lower levels of viral RNA showed lower numbers of T-cells and CD8 cells and were enriched for fibrosis-associated genes. The study highlights the need to assess both pulmonary viral load and immune response in patients with severe COVID-19 infection.