TY - JOUR T1 - Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load JF - bioRxiv DO - 10.1101/2023.05.24.542181 SP - 2023.05.24.542181 AU - Vasanthi Avadhanula AU - Chad J. Creighton AU - Laura Ferlic-Stark AU - Richard Sucgang AU - Yiqun Zhang AU - Divya Nagaraj AU - Erin G. Nicholson AU - Anubama Rajan AU - Vipin Kumar Menon AU - Harshavardhan Doddapaneni AU - Donna Marie Muzny AU - Ginger Metcalf AU - Sara Joan Javornik Cregeen AU - Kristi Louise Hoffman AU - Richard A Gibbs AU - Joseph Petrosino AU - Pedro A Piedra Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/05/25/2023.05.24.542181.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest.COVID-19Coronavirus disease 19SARS-CoV-2severe acute respiratory syndrome coronavirus 2 ER -