Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.

TitleLongitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.
Publication TypeJournal Article
Year of Publication2023
AuthorsAvadhanula, V, Creighton, CJ, Ferlic-Stark, L, Sucgang, R, Zhang, Y, Nagaraj, D, Nicholson, EG, Rajan, A, Menon, VKumar, Doddapaneni, H, Muzny, DM, Metcalf, GA, Cregeen, SJoan Javor, Hoffman, KLouise, Gibbs, RA, Petrosino, J, Piedra, PA
Date Published2023 May 25

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.

Alternate JournalbioRxiv
PubMed ID37292999
PubMed Central IDPMC10245966
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States