Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

ABSTRACT: Post-acute sequelae of SARS-CoV-2 infection are debilitating, clinically heterogeneous, and of unknown molecular etiology. A transcriptome-wide investigation was performed in acutely infected patients followed clinically into the post-acute period. Distinct gene-expression signatures of post-acute sequelae were already present in whole-blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell associated gene-expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in subjects with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE215865 | GEO | 2022/12/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.

2013-05-28 | E-GEOD-11704 | biostudies-arrayexpress

Maladaptive TGF-β Signals to the Alveolar Epithelium Drive Fibrosis after COVID-19 Infection

Project description:We have performed single cell RNA sequencing on explant tissue of post-acute sequelae SARS-CoV-2 infection (PASC) patients. The study focused on epithelial cells (Epcam+) and immune cells (CD45+) cells. We further compared our PASC sample with Donor and IPF samples from GSE146981 and GSE135893.

2023-05-15 | GSE224955 | GEO

Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects

Project description:Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer’s disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

2023-07-11 | GSE236562 | GEO

Transcriptome profiling of lungs from young and aged hamster

Project description:Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263 depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19.

2023-04-30 | GSE230301 | GEO

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Project description:Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

2024-01-12 | MTBLS850 | MetaboLights

Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

2013-05-28 | GSE11704 | GEO

Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress

Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters

Project description:Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263, a B cell lymphoma-2 family inhibitor, depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower expression of angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19. As several senolytics have recently moved into early-stage clinical trials, our present findings have clear clinical relevance.

2023-07-03 | PXD041973 | Pride

Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters

Project description:Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263, a B cell lymphoma-2 family inhibitor, depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower expression of angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19. As several senolytics have recently moved into early-stage clinical trials, our present findings have clear clinical relevance.

2023-07-03 | PXD041777 | Pride

Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2

Project description:Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (LC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple “omics” assays (CyTOF, RNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of unvaccinated individuals with clear LC and non-LC clinical trajectories, 8 months following infection. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that LC individuals exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals harbored increased frequencies of CD4+ T cells poised to home to inflamed tissues, and of exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and they, but not non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of a persistent reservoir of SARS-CoV-2, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating disease.

2023-02-09 | GSE224615 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data