Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature

Cappuccio, Antonio; Chawla, Daniel G.; Chen, Xi; Rubenstein, Aliza B.; Cheng, Wan Sze; Mao, Weiguang; Burke, Thomas W.; Tsalik, Ephraim L.; Petzold, Elizabeth; Henao, Ricardo; McClain, Micah T.; Woods, Christopher W.; Chikina, Maria; Troyanskaya, Olga G.; Sealfon, Stuart C.; Kleinstein, Steven H.; Zaslavsky, Elena

doi:10.1016/j.cels.2022.11.008

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“… 15 , 19 These studies and others have been critical to build foundational understanding of the pathogenesis underlying the varying clinical manifestations of this novel disease. 17 , 19 , 20 …”

Section: Introductionmentioning

confidence: 99%

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

McClain,

Zhbannikov,

Satterwhite

et al. 2024

iScience

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Section: Introductionmentioning

confidence: 99%

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

McClain,

Zhbannikov,

Satterwhite

et al. 2024

iScience

Self Cite

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Benchmarking transcriptional host response signatures for infection diagnosis

et al. 2022

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SARS-CoV-2 human challenge reveals single-gene blood transcriptional biomarkers that discriminate early and late phases of acute respiratory viral infections

Rosenheim,

Gupta,

Thakker

et al. 2023

Preprint

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Evaluation of host-response blood transcriptional signatures of viral infection have so far failed to test whether these biomarkers reflect different biological processes that may be leveraged for distinct translational applications. We addressed this question in the SARS-CoV-2 human challenge model. We found differential time profiles for interferon (IFN) stimulated blood transcriptional responses represented by measurement of single genes. MX1 transcripts correlated with a rapid and transient wave of type 1 IFN stimulated genes (ISG) across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, showed a delayed but sustained response restricted to myeloid peripheral blood mononuclear cells, attributable to gene and cell-specific epigenetic regulation. These findings were reproducible in diverse respiratory virus challenges, and in natural infection with SARS-CoV-2 or unselected respiratory viruses. The MX1 response achieved superior diagnostic accuracy in early infection, correlation with viral load and identification of virus culture positivity, with potential to stratify patients for time sensitive antiviral treatment. IFI27 achieved superior diagnostic accuracy across the time course of symptomatic infection. Compared to blood, measurement of these responses in nasal mucosal samples was less sensitive and did not discriminate between early and late phases of infection.

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Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature

Cited by 3 publications

References 59 publications

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

Benchmarking transcriptional host response signatures for infection diagnosis

SARS-CoV-2 human challenge reveals single-gene blood transcriptional biomarkers that discriminate early and late phases of acute respiratory viral infections

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