Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alterations in circulating monocytes predict COVID-19 severity and include chromatin modifications still detectable six months after recovery

ABSTRACT: An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room (ER) arrival, monocytes showed decreased surface molecules expression, including HLA-DR, in association to an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. These alterations were mostly normalized in post-COVID-19 patients, 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory, tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface markers and low IRF1 gene transcription in circulating monocytes at ER defined a COVID-19 patients group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patients stratification and to designing innate immunity-focused therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180523 | GEO | 2021/10/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Alterations in circulating monocytes predict COVID-19 severity and include chromatin modifications still detectable six months after recovery

Project description:An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room (ER) arrival, monocytes showed decreased surface molecules expression, including HLA-DR, in association to an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. These alterations were mostly normalized in post-COVID-19 patients, 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory, tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface markers and low IRF1 gene transcription in circulating monocytes at ER defined a COVID-19 patients group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patients stratification and to designing innate immunity-focused therapies.

2021-07-22 | GSE180594 | GEO

Linear epitope-specific IgG responses to SARS-CoV-2 and related human coronaviruses in human COVID-19 convalescent sera

Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.

2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress

A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients

Project description:We utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. Our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.

2021-03-20 | E-MTAB-10169 | biostudies-arrayexpress

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

ACE2-independent SARS-CoV-2 virus entry through cell surface GRP78 on monocytes - evidence from a translational clinical and experimental approach

Project description:SARS-CoV-2 infects host cells via an ACE2/TMPRSS2 entry mechanism. Monocytes and macrophages, which play a key role during severe COVID-19 express only low or no ACE2, suggesting alternative entry mechanisms in these cells. In silico analyses predicted GRP78, which is constitutively expressed on monocytes and macrophages, to be a potential candidate receptor for SARS-CoV-2 virus entry. To confirm the hypothesis, we conducted high-throughput RNA sequence to characterize the role of GRP78 in monocytes function in COVID-19 patients

2023-12-13 | GSE245922 | GEO

Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients

Project description:Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.

2021-05-03 | GSE155897 | GEO

CYP19A1 mediated sex hormone metabolism promotes severe disease outcome in SARS-CoV-2 infected male golden hamsters

Project description:Male sex belongs to one of the risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a host factor that contributes to worsened disease outcome in male hamsters. SARS-CoV-2 infection increases CYP19A1 transcription most prominently in the lungs of male animals, which correlates with reduced circulating testosterone and increased circulating estradiol levels. Dysregulated sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated sex hormone levels and was associated with improved lung function in male but not female animals compared to placebo controls. Whole-lung transcriptome analysis in letrozole treated versus placebo treated control groups revealed key pathways associated with improved lung health in males. To seek translation of these findings into humans, we analyzed autopsy-derived lung samples of COVID-19 cases from three independent study sites. We found that CYP19A1 transcription and protein expression is strongly elevated in the lungs of men who died with COVID-19 as compared to females or non-COVID-19 controls. Our findings highlight the role of the lung as a yet unrecognized but critical organ involved in metabolic responses against respiratory virus infections. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.

2022-01-21 | E-MTAB-11162 | biostudies-arrayexpress

Monocyte-mediated thrombosis linked to circulating tissue factor and immune-paralysis in COVID-19

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and are associated with inflammation and coagulopathy and high incidence of thrombosis. Myeloid cells (Mϕ) help coordinate the initial immune response in COVID-19. Although we appreciate that Mϕ lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown. In this study, we employed systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19. In a cohort of COVID-19 subjects (n=35), circulating markers of inflammation (CCL23, IL-6) and vascular dysfunction (ACE2, tissue factor [TF]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell (WBC) counts were similar between COVID-19 groups, CD14+ monocytes from severe COVID-19 subjects expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1, C5AR1, C5AR2, and TF in severe COVID-19 subjects compared with controls. Using “stress” transcriptomics, we found that circulating immune cells from severe COVID-19 subjects had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to Toll-like receptor (TLR) activation. Finally, sera from severe (but not mild) COVID-19 subjects activated human monocytes and induced TF expression. Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.

2024-01-23 | GSE247186 | GEO

Baricitinib attenuates the proinflammatory phase1 of COVID-19 driven by lung-infiltrating monocytes

Project description:COVID-19 patients are generally asymptomatic during initial SARS-CoV-2 replication, but may suffer severe immunopathology after the virus has receded and blood monocytes have infiltrated the airways. In the bronchoalveolar lavage fluid from patients with severe COVID-19, lung-infiltrating monocytes expressed high mRNA levels encoding inflammatory mediators, including CXCL8and IL-1ß, and contained SARS-CoV-2transcripts. To study this process in more depth, we developed a novel organotypic model whereby primary human blood monocytes are transmigrated across a differentiated human lung epithelium infected by SARS-CoV-2. Infiltrating monocytes acquiredSARS-CoV-2 from the epithelium and upregulated expression and secretion of inflammatory mediators includingCXCL8 and IL-1ß, mirroring in vivo data. The JAK1/2inhibitor baricitinib gained emergency use authorization by the FDA for the treatment of COVID-19 originally in combination with the antiviral remdesivir, and recently as a stand-alone treatment. To explore the mechanisms by which baricitinib alone or in combination with remdesivir may result in more favorable disease outcomes, we leveraged this model to characterize viral burden, gene expression and inflammatory mediator secretion by lung epithelial cells and infiltrating monocytes. As expected, remdesivir decreased viral burden in both the epithelium and monocytes, while baricitinib enhanced antiviral signaling and decreased specific inflammatory mediators in monocytes. Combined use of baricitinib and remdesivir enhanced the rate of virus clearance from SARS-CoV-2-positivemonocytes. Taken together, baricitinib enhances the antiviral state of monocytes infiltrating the COVID-19 lung, while decreasing the expression of inflammatory mediators, thus limiting the likelihood of a cytokine storm and ensuing acute respiratory distress syndrome (ARDS).

2021-10-30 | GSE186460 | GEO

Deficient radiation transcription response in COVID-19 patients

Project description:The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalised patients is complex due to the heterogeneous course of COVID-19. Low-dose radiotherapy (LD-RT) is known to dampen localised chronic inflammation, and has been suggested to be used to reduce lung inflammation in COVID-19 patients. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk. We generated gene expression profiles from circulating leukocytes of hospitalised COVID-19 patients and healthy donors. The p53 signalling pathway was found to be dysregulated, with mRNA levels of p53, ATM and CHK2 being lower in COVID-19 patients. Several key p53 target genes involved in cell cycle arrest, apoptosis and p53 feedback inhibition were up-regulated in COVID-19 patients, while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 h after X-ray exposure ex-vivo to both low (100 mGy) or high (2 Gy) doses. In conclusion, SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed COVID-19 patients.

2023-02-01 | GSE223885 | 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