Publication date: Jan 17, 2025
Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes correlated with SARS-CoV-2 viral load over time were similarly differentially expressed across independent datasets of SARS-CoV-2 infected lung and upper airway cells, from both in vitro systems and patient samples. We also generated expression data on the human nose organoid model during SARS-CoV-2 infection. The human nose organoid-generated host transcriptional response captured many aspects of responses observed in the above patient samples, while suggesting the existence of distinct host responses to SARS-CoV-2 depending on the cellular context, involving both epithelial and cellular immune responses. Our findings provide a catalog of SARS-CoV-2 host response genes changing over time and magnitude of these host responses were significantly correlated to viral load.
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Concepts | Keywords |
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Covid | Adult |
Driving | COVID-19 |
Low | Female |
Pathogenic | Host-Pathogen Interactions |
Viral | Humans |
Longitudinal Studies | |
Lung | |
Male | |
SARS-CoV-2 | |
Viral Load |
Semantics
Type | Source | Name |
---|---|---|
disease | IDO | host |
disease | MESH | SARS-CoV-2 infection |
pathway | REACTOME | SARS-CoV-2 Infection |
disease | MESH | viral load |
disease | MESH | infection |
disease | IDO | history |
disease | IDO | process |
pathway | REACTOME | Reproduction |
disease | MESH | asymptomatic infection |
disease | MESH | death |
disease | MESH | obesity |
disease | MESH | cardiovascular disease |
disease | IDO | replication |
disease | MESH | viral shedding |
pathway | KEGG | Viral replication |
pathway | REACTOME | Apoptosis |
pathway | KEGG | p53 signaling pathway |
disease | MESH | complications |
disease | IDO | pathogen |