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

Author:

Avadhanula VasanthiORCID,Creighton Chad J.,Ferlic-Stark Laura,Sucgang Richard,Zhang Yiqun,Nagaraj Divya,Nicholson Erin G.,Rajan Anubama,Menon Vipin Kumar,Doddapaneni Harshavardhan,Muzny Donna Marie,Metcalf Ginger,Cregeen Sara Joan Javornik,Hoffman Kristi Louise,Gibbs Richard A,Petrosino Joseph,Piedra Pedro A

Abstract

AbstractCurrent 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.

Publisher

Cold Spring Harbor Laboratory

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