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PROVIDER: PRJDB12809 | ENA |
REPOSITORIES: ENA
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Project description:<p>The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the 'new normal'. The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO) and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (6 cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least 6 machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.</p>
2024-08-26 | MTBLS3305 | MetaboLights
Project description:Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood. Here we use systems immunology approaches, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences), to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean: 151 days after diagnosis) and 40 age- and sex-matched controls who never had COVID-19. At baseline and independent of time since COVID-19, recoverees had elevated T-cell activation signatures and lower expression of innate immune genes in monocytes. COVID-19-recovered males had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy male and COVID-19-recovered females, partly because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated pre-vaccination frequencies of "virtual memory" like CD8+ T-cells poised to produce more IFNg upon IL-15 stimulation. In addition, the expression of the repressed innate immune genes in monocytes increased by day 1 through day 28 post-vaccination in recoverees, thus moving towards the pre-vaccination baseline of healthy controls. In contrast, these genes decreased on day 1 and returned to the baseline by day 28 in controls. Our study reveals sex-dimorphic impacts of prior mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points impacting future immune responses in an antigen-agnostic manner.
2022-03-09 | GSE194378 | GEO
Project description:Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood. Here we use systems immunology approaches, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences), to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean: 151 days after diagnosis) and 40 age- and sex-matched controls who never had COVID-19. At baseline and independent of time since COVID-19, recoverees had elevated T-cell activation signatures and lower expression of innate immune genes in monocytes. COVID-19-recovered males had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy male and COVID-19-recovered females, partly because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated pre-vaccination frequencies of "virtual memory" like CD8+ T-cells poised to produce more IFNg upon IL-15 stimulation. In addition, the expression of the repressed innate immune genes in monocytes increased by day 1 through day 28 post-vaccination in recoverees, thus moving towards the pre-vaccination baseline of healthy controls. In contrast, these genes decreased on day 1 and returned to the baseline by day 28 in controls. Our study reveals sex-dimorphic impacts of prior mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points impacting future immune responses in an antigen-agnostic manner.
2023-01-04 | GSE206265 | GEO
Project description:An increasing body of literature suggests that innate immune cells such as monocytes undergo epigenetic reprogramming following challenges such as infection or vaccination. We performed omni-ATACseq to assess chromatin accessibility in classical monocytes (CD14+CD16-) isolated from healthy participants before vaccination or 28 days following the second dose of an mRNA or adenoviral vectored COVID-19 vaccine.
2023-07-23 | GSE225165 | GEO
Project description:This experiment aims to understand transcriptomic signatures associated with COVID-19 infected individuals with cancer. Samples were taken before the third dose of the COVID-19 mRNA vaccination and examined differences between samples with a breakthrough infection versus without breakthrough infection, as well as subjects with haematological malignancies versus solid tumours. The results found that cancer patients with haematological malignancies are at increased risk of breakthrough infections.
2025-04-17 | E-MTAB-14545 | biostudies-arrayexpress
Project description:Pre-vaccination SARS-CoV-2 infection can boost protection elicited by COVID-19 vaccination and post-vaccination breakthrough SARS-CoV-2 infection can boost existing immunity conferred by COVID-19 vaccination. Such ‘hybrid immunity’ is effective against SARS-CoV-2 variants. In order to understand ‘hybrid immunity’ at the molecular level we studied the complementarity determining regions (CDR) of anti-RBD (receptor binding domain) antibodies isolated from individuals with ‘hybrid immunity’ as well as from ‘naive’ (notSARS-CoV-2 infected) vaccinated individuals. CDR analysis was done by liquid chromatography/mass spectrometry-mass spectrometry.
2023-02-08 | PXD038849 | Pride
Project description:Background/Objectives: Synthetic mRNA vaccines have raised concerns regarding prolonged spike protein expression, immune activation, and potential off-target effects. This study investigates transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA COVID-19 vaccination. Methods: Bulk RNA sequencing was performed on peripheral blood from two patient groups: individuals with new-onset nonmalignant adverse events and individuals newly diagnosed with cancer post-vaccination. A control group of healthy individuals was used for comparison. Differential gene expression was analyzed using DESeq2, and Gene Set Enrichment Analysis (GSEA) was conducted using the MSigDB database and custom gene sets. Results: Both vaccine patient groups displayed widespread transcriptional dysregulation. In the nonmalignant adverse event group, hallmark enrichments included mitochondrial dysfunction, proteasome-mediated stress, transcriptomic instability, and systemic inflammation. The cancer group exhibited additional hallmarks of genomic instability, and epigenetic reprogramming. Nonsense-mediated decay (NMD), ribosomal stress, and MYC activation were prominent in both groups, while immune signaling via TLRs and type I interferons was particularly elevated in cancer patients.
2025-08-08 | GSE304973 | GEO
Project description:Daily transcriptomic profiling was conducted on whole blood collected from COVID-19 cases. Whole blood was collected in Tempus Blood RNA tubes, and RNA was extracted from whole blood using the Tempus Spin RNA Isolation Kit. Healthy controls consisted of participants of a measles, mumps and rubella re-vaccination study. Pre-vaccination whole blood was collected and processed and analyzed as above.
2020-03-27 | E-MTAB-8871 | biostudies-arrayexpress
Project description:Daily transcriptomic profiling was conducted on whole blood collected from COVID-19 cases. Whole blood was collected in Tempus Blood RNA tubes, and RNA was extracted from whole blood using the Tempus Spin RNA Isolation Kit. Healthy controls consisted of participants of a measles, mumps and rubella re-vaccination study. Pre-vaccination whole blood was collected and processed and analyzed as above.
2021-02-24 | E-MTAB-9719 | biostudies-arrayexpress
Project description:Whole transcriptome analysis performed on lung samples from dead covid-19 patients and healthy non-covid-19 individuals of multiple age groups.
2022-05-31 | GSE183533 | GEO