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

Avadhanula, V.; Creighton, C. J.; Ferlic-Stark, L.; Sucgang, R.; Zhang, Y.; Nagaraj, D.; Nicholson, E. G.; Rajan, A.; Menon, V. K.; Doddapaneni, H.; Muzny, D. M.; Metcalf, G. A.; Cregeen, S. J. J.; Hoffman, K. L.; Gibbs, R. A.; Petrosino, J. J.; Piedra, P. A.

doi:10.1101/2023.05.24.542181

bioRxiv · 10.1101/2023.05.24.542181

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

Avadhanula, V.·Creighton, C. J.·Ferlic-Stark, L.·Sucgang, R.·Zhang, Y.·Nagaraj, D.·Nicholson, E. G.·Rajan, A.·Menon, V. K.·Doddapaneni, H.·Muzny, D. M.·Metcalf, G. A.·Cregeen, S. J. J.·Hoffman, K. L.·Gibbs, R. A.·Petrosino, J. J.·Piedra, P. A.

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Abstract

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.

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Avadhanula, V., Creighton, C. J., Ferlic-Stark, L., Sucgang, R., Zhang, Y., Nagaraj, D., Nicholson, E. G., Rajan, A., Menon, V. K., Doddapaneni, H., Muzny, D. M., Metcalf, G. A., Cregeen, S. J. J., Hoffman, K. L., Gibbs, R. A., Petrosino, J. J., Piedra, P. A.. 2023-05-25. Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load. https://doi.org/10.1101/2023.05.24.542181

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