Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA981515 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. We conducted a longitudinal study to investigate gene expression patterns during the acute SARS-CoV-2 illness. The cases included SARS-CoV-2 infected individuals with an extremely high viral load early in their illness matched to individuals who either had a low SARS-CoV-2 viral load early in their infection or were otherwise stable patients who tested negative for SARS-CoV-2 prior to their outpatient surgical or aerosol generating procedure. We detected hundreds of up-regulated genes that were highly correlated to the SARS-CoV-2 viral load. Many of these up-regulated genes were enriched in cellular pathways involved in the innate immune response, antiviral interferon and cytokine signaling, and cell death.
2023-09-28 | GSE234486 | GEO
Project description: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.
| S-EPMC10245966 | biostudies-literature
Project description:The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time.
2023-04-01 | E-MTAB-12791 | biostudies-arrayexpress
Project description:We examined host gene expression across infection status, viral load, age, and sex among RNA-sequencing profiles of nasopharyngeal swabs from 430 individuals with SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong interferon-driven antiviral response and reduced transcription of ribosomal proteins. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load. B cells and neutrophils were higher in patients with lower viral load. Older individuals had reduced expression of chemokines CXCL9/10/11, their cognate receptor CXCR3, and CD8A and granzyme B. Males had reduced B and NK cell-specific transcripts and increased NFkB inhibitors. Our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.
2020-06-22 | GSE152075 | GEO
Project description:The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We visualized viral RNA by in situ hybridization and assessed the immune infiltrate using immunohistochemistry and total RNA sequencing on five COVID-19 positive patients. Patients with high levels of viral RNA showed hyaline membranes on histology, extensive pneumocyte loss, low T-cell numbers and were enriched for the interferon gene signature, while patients with lower levels of viral RNA showed lower numbers of T-cells and CD8 cells and were enriched for fibrosis-associated genes. The study highlights the need to assess both pulmonary viral load and immune response in patients with severe COVID-19 infection.
2020-05-12 | GSE150316 | GEO
Project description:Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.
2023-01-11 | GSE196456 | GEO
Project description:Gene expression profile was performed on peripheral blood mononuclear cells from HIV-infected patients selected in a cross-sectional analysis according to their viral load.
2004-01-09 | E-MEXP-53 | biostudies-arrayexpress
Project description:Longitudinal Study of Leukocyte DNA Methylation and Biomarkers for Cancer Risk in Older Adults
| PRJNA541270 | ENA
Project description:Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-PCR cycle threshold (Ct) of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.
2021-07-30 | GSE173310 | GEO
Project description:BackgroundMultiple waves of the COVID-19 epidemic have hit most countries by the end of 2021. Most of those waves are caused by emergence and importation of new variants. To prevent importation of new variants, combination of border control and contact tracing is essential. However, the timing of infection inferred by interview is influenced by recall bias and hinders the contact tracing process.MethodsWe propose a novel approach to infer the timing of infection, by employing a within-host model to capture viral load dynamics after the onset of symptoms. We applied this approach to ascertain secondary transmission which can trigger outbreaks. As a demonstration, the 12 initial reported cases in Singapore, which were considered as imported because of their recent travel history to Wuhan, were analyzed to assess whether they are truly imported.ResultsOur approach suggested that 6 cases were infected prior to the arrival in Singapore, whereas other 6 cases might have been secondary local infection. Three among the 6 potential secondary transmission cases revealed that they had contact history to previously confirmed cases.ConclusionsContact trace combined with our approach using viral load data could be the key to mitigate the risk of importation of new variants by identifying cases as early as possible and inferring the timing of infection with high accuracy.
| S-EPMC9331019 | biostudies-literature