Single-cell transcriptome analysis of bronchoalveolar lavage during early SARS-CoV-2 infection.

The COVID-19 pandemic, triggered by the SARS-CoV-2 virus, has led to global consequences since its emergence in late 2019, impacting health, economies, and societies worldwide. Understanding the early responses following infection will provide crucial insights into the immune mechanisms governing disease progression and protection. We employed the single-cell RNA-sequencing approach using bronchoalveolar lavage cells of rhesus macaques at 0-3 days post-infection (dpi) in a non-human primate model of SARS-CoV-2. Our results show the increased abundance of two subsets of macrophages that express IFN-responsive gene signatures, inflammatory dendritic cells (DCs), plasmacytoid DCs, and conventional DCs at 3 dpi, coinciding with peak viremia. Moreover, our investigation underscores the enrichment of IFN-α/β, IFN-γ, and IL-1 signaling pathways within myeloid populations at 2-3 dpi in comparison to baseline. These findings substantially deepen our comprehension, elucidating the transcriptional landscape at the single-cell level during the early phases of COVID-19 within a highly relevant model. IMPORTANCE: Understanding the immune response in the early stages of COVID-19 is crucial for developing better treatments and vaccines. In this study, we used advanced single-cell RNA sequencing to examine the immune cells in the lungs of rhesus macaques, a model for human SARS-CoV-2 infection, within the first few days after infection. We identify key immune cell types, such as macrophages and dendritic cells, that are activated early on and produce important signals to fight the virus. These findings help clarify how the immune system responds to SARS-CoV-2 at the single-cell level, offering valuable insights that could guide future therapeutic approaches.