Human SARS-CoV-2 challenge resolves local and systemic response dynamics
Updated June 17, 2024The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In our unique COVID-19 human challenge study we used single cell genomics of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes in cell type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific timepoints or infection status. We observed that the interferon response in blood precedes the nasopharynx, and that nasopharyngeal immune infiltration occurred early in transient but later in sustained infection, and thus correlated with preventing sustained infection. Ciliated cells showed an acute response phase, upregulated MHC class II while infected, and were most permissive for viral replication, whilst nasal T cells and macrophages were infected non-productively. We resolve 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our novel computational pipeline (Cell2TCR) identifies activated antigen-responding clonotype groups and motifs in any dataset. Together, we show that our detailed time series data ( covid19cellatlas.org ) can serve as a “Rosetta stone” for the epithelial and immune cell responses, and reveals early dynamic responses associated with protection from infection.
Human SARS-CoV-2 challenge resolves local and systemic response dynamics (Official HCA Publication)
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Atlas
Analysis Portals
NoneProject Label
SARSCoV2ResponseDynamicsSpecies
Homo sapiens
Sample Type
specimens
Anatomical Entity
Organ Part
Unspecified
Selected Cell Types
Unspecified
Disease Status (Specimen)
COVID-19
Disease Status (Donor)
COVID-19
Development Stage
human adult stage
Library Construction Method
Nucleic Acid Source
Paired End
falseAnalysis Protocol
processed_matrix_generation, raw_matrix_generation_PBMC, raw_matrix_generation_alfa_beta, raw_matrix_generation_gamma_delta, raw_matrix_generation_nasalFile Format
Cell Count Estimate
606.1kDonor Count
16