homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context
Summary: Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understo...
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Elsevier
2025-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642400567X |
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| author | Fang Yun Lim Hannah G. Lea Ashley M. Dostie Soo-Young Kim Tammi L. van Neel Grant W. Hassan Meg G. Takezawa Lea M. Starita Karen N. Adams Michael Boeckh Joshua T. Schiffer Ollivier Hyrien Alpana Waghmare Erwin Berthier Ashleigh B. Theberge |
| author_facet | Fang Yun Lim Hannah G. Lea Ashley M. Dostie Soo-Young Kim Tammi L. van Neel Grant W. Hassan Meg G. Takezawa Lea M. Starita Karen N. Adams Michael Boeckh Joshua T. Schiffer Ollivier Hyrien Alpana Waghmare Erwin Berthier Ashleigh B. Theberge |
| author_sort | Fang Yun Lim |
| collection | DOAJ |
| description | Summary: Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens. Methods: We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups. Findings: Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals. Interpretation: We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies. Funding: This study was funded by R35GM128648 to ABT for in-lab developments of homeRNA and data analysis, a Packard Fellowship for Science and Engineering from the David and Lucile Packard Foundation to ABT for the study execution, sample collection, and analysis, and R01AI153087 to AW for data analysis. |
| format | Article |
| id | doaj-art-62bedb1fe5bc44df8c10304101e57409 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-62bedb1fe5bc44df8c10304101e574092025-01-19T06:26:12ZengElsevierEBioMedicine2352-39642025-02-01112105531homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in contextFang Yun Lim0Hannah G. Lea1Ashley M. Dostie2Soo-Young Kim3Tammi L. van Neel4Grant W. Hassan5Meg G. Takezawa6Lea M. Starita7Karen N. Adams8Michael Boeckh9Joshua T. Schiffer10Ollivier Hyrien11Alpana Waghmare12Erwin Berthier13Ashleigh B. Theberge14Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Chemistry, University of Washington, Seattle, WA, USADepartment of Chemistry, University of Washington, Seattle, WA, USA; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USADepartment of Chemistry, University of Washington, Seattle, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USADepartment of Chemistry, University of Washington, Seattle, WA, USADepartment of Chemistry, University of Washington, Seattle, WA, USADepartment of Chemistry, University of Washington, Seattle, WA, USABrotman Baty Institute, University of Washington, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USADepartment of Chemistry, University of Washington, Seattle, WA, USA; Institute of Translational Health Sciences, School of Medicine, University of Washington, Seattle, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA; Corresponding author. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.Department of Chemistry, University of Washington, Seattle, WA, USA; Corresponding author.Department of Chemistry, University of Washington, Seattle, WA, USA; Department of Urology, University of Washington, Seattle, WA, USA; Corresponding author. Department of Chemistry, University of Washington, Seattle, WA, USA.Summary: Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens. Methods: We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups. Findings: Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals. Interpretation: We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies. Funding: This study was funded by R35GM128648 to ABT for in-lab developments of homeRNA and data analysis, a Packard Fellowship for Science and Engineering from the David and Lucile Packard Foundation to ABT for the study execution, sample collection, and analysis, and R01AI153087 to AW for data analysis.http://www.sciencedirect.com/science/article/pii/S235239642400567XBlood transcriptional responseSelf-blood collectionPresymptomaticRespiratory infectionshomeRNASARS-CoV-2 |
| spellingShingle | Fang Yun Lim Hannah G. Lea Ashley M. Dostie Soo-Young Kim Tammi L. van Neel Grant W. Hassan Meg G. Takezawa Lea M. Starita Karen N. Adams Michael Boeckh Joshua T. Schiffer Ollivier Hyrien Alpana Waghmare Erwin Berthier Ashleigh B. Theberge homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context EBioMedicine Blood transcriptional response Self-blood collection Presymptomatic Respiratory infections homeRNA SARS-CoV-2 |
| title | homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context |
| title_full | homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context |
| title_fullStr | homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context |
| title_full_unstemmed | homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context |
| title_short | homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort studyResearch in context |
| title_sort | homerna self blood collection enables high frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection a prospective cohort studyresearch in context |
| topic | Blood transcriptional response Self-blood collection Presymptomatic Respiratory infections homeRNA SARS-CoV-2 |
| url | http://www.sciencedirect.com/science/article/pii/S235239642400567X |
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