tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Chad J Creighton[SUP] 2 3 4 [/SUP], Laura Ferlic-Stark[SUP] 1 [/SUP], Divya Nagaraj[SUP] 1 [/SUP], Yiqun Zhang[SUP] 2 [/SUP], Richard Sucgang[SUP] 5 [/SUP], Erin G Nicholson[SUP] 1 6 [/SUP], Anubama Rajan[SUP] 1 [/SUP], Vipin Kumar Menon[SUP] 4 7 [/SUP], Harshavardhan Doddapaneni[SUP] 4 7 [/SUP], Donna Marie Muzny[SUP] 4 7 [/SUP], Ginger A Metcalf[SUP] 4 7 [/SUP], Sara Joan Javornik Cregeen[SUP] 1 [/SUP], Kristi Louise Hoffman[SUP] 1 [/SUP], Richard A Gibbs[SUP] 4 7 [/SUP], Joseph F Petrosino[SUP] 1 [/SUP], Pedro A Piedra[SUP] 1 6 [/SUP]
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[SUP] 1 [/SUP], Chad J Creighton[SUP] 2 3 4 [/SUP], Laura Ferlic-Stark[SUP] 1 [/SUP], Divya Nagaraj[SUP] 1 [/SUP], Yiqun Zhang[SUP] 2 [/SUP], Richard Sucgang[SUP] 5 [/SUP], Erin G Nicholson[SUP] 1 6 [/SUP], Anubama Rajan[SUP] 1 [/SUP], Vipin Kumar Menon[SUP] 4 7 [/SUP], Harshavardhan Doddapaneni[SUP] 4 7 [/SUP], Donna Marie Muzny[SUP] 4 7 [/SUP], Ginger A Metcalf[SUP] 4 7 [/SUP], Sara Joan Javornik Cregeen[SUP] 1 [/SUP], Kristi Louise Hoffman[SUP] 1 [/SUP], Richard A Gibbs[SUP] 4 7 [/SUP], Joseph F Petrosino[SUP] 1 [/SUP], Pedro A Piedra[SUP] 1 6 [/SUP]
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.