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PLoS One
. 2025 Jan 16;20(1):e0317033.
doi: 10.1371/journal.pone.0317033. eCollection 2025. Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
Vasanthi Avadhanula 1 , Chad J Creighton 2 3 4 , Laura Ferlic-Stark 1 , Divya Nagaraj 1 , Yiqun Zhang 2 , Richard Sucgang 5 , Erin G Nicholson 1 6 , Anubama Rajan 1 , Vipin Kumar Menon 4 7 , Harshavardhan Doddapaneni 4 7 , Donna Marie Muzny 4 7 , Ginger A Metcalf 4 7 , Sara Joan Javornik Cregeen 1 , Kristi Louise Hoffman 1 , Richard A Gibbs 4 7 , Joseph F Petrosino 1 , Pedro A Piedra 1 6
Affiliations
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.
. 2025 Jan 16;20(1):e0317033.
doi: 10.1371/journal.pone.0317033. eCollection 2025. Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
Vasanthi Avadhanula 1 , Chad J Creighton 2 3 4 , Laura Ferlic-Stark 1 , Divya Nagaraj 1 , Yiqun Zhang 2 , Richard Sucgang 5 , Erin G Nicholson 1 6 , Anubama Rajan 1 , Vipin Kumar Menon 4 7 , Harshavardhan Doddapaneni 4 7 , Donna Marie Muzny 4 7 , Ginger A Metcalf 4 7 , Sara Joan Javornik Cregeen 1 , Kristi Louise Hoffman 1 , Richard A Gibbs 4 7 , Joseph F Petrosino 1 , Pedro A Piedra 1 6
Affiliations
- PMID: 39820858
- PMCID: PMC11737797
- DOI: 10.1371/journal.pone.0317033
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.