Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19 Data Access Committee
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PROVIDER: EGAC00001002503 | EGA |
REPOSITORIES: EGA
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Project description:The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body's immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival.
| S-EPMC9160963 | biostudies-literature
Project description:Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.
| EGAS00001005971 | EGA
Project description:The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, causing a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), besides an exacerbated and uncontrolled systemic inflammation which in some cases induce lethal cytokine storm. Although vaccines have clearly had a beneficial effect on disease development, there is still a high percentage of patients who develop pathology related to ineffective immune system response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in immune system activation further its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins and controls their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase of serum global neddylation levels of COVID-19 patients particularly associated in the early response of the infection. In addition, the results showed that overactivation of neddylation control activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) derived from COVID-19 patients. Inhibition of neddylation and subsequent avoidance of activation of PBMCs, which reduces cytokine production and proteome modulation, may therefore be a critical mechanism and an efficient therapeutic approach to immunomodulate COVID -19 patients and avoid the much-feared cytokine storm.
2022-08-02 | PXD033673 | Pride
Project description:BackgroundThe current endpoints for therapeutic trials of hospitalized COVID-19 patients capture only part of the clinical course of a patient and have limited statistical power and robustness.MethodsWe specify proportional odds models for repeated measures of clinical status, with a common odds ratio of lower severity over time. We also specify the proportional hazards model for time to each level of improvement or deterioration of clinical status, with a common hazard ratio for overall treatment benefit. We apply these methods to Adaptive COVID-19 Treatment Trials.ResultsFor remdesivir versus placebo, the common odds ratio was 1.48 (95% confidence interval (CI) = 1.23-1.79; p < 0.001), and the common hazard ratio was 1.27 (95% CI = 1.09-1.47; p = 0.002). For baricitinib plus remdesivir versus remdesivir alone, the common odds ratio was 1.32 (95% CI = 1.10-1.57; p = 0.002), and the common hazard ratio was 1.30 (95% CI = 1.13-1.49; p < 0.001). For interferon beta-1a plus remdesivir versus remdesivir alone, the common odds ratio was 0.95 (95% CI = 0.79-1.14; p = 0.56), and the common hazard ratio was 0.98 (95% CI = 0.85-1.12; p = 0.74).ConclusionsThe proposed methods comprehensively characterize the treatment effects on the entire clinical course of a hospitalized COVID-19 patient.
| S-EPMC11304635 | biostudies-literature
Project description:The human immune system protects the body against invasive organisms and kicks into a hyperactive mode in COVID-19 patients, particularly in those who are critically sick. Therapeutic regimens directed at the hyperactive immune system have been found to be effective in the treatment of patients with COVID-19. An evolving potential treatment option is therapy with mesenchymal stem cells (MSCs) due to their regenerative and reparative ability in epithelial cells. Clinical trials have reported the safe usage of MSC therapy. Systemic effects of MSC treatment have included a reduction in pro-inflammatory cytokines and a decrease in the levels of CRP, IL-6, and lactase dehydrogenase, which function as independent biomarkers for COVID-19 mortality and respiratory failure.
| S-EPMC9298490 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation and host immune response in acute COVID-19 cases. 3 brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering >99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed transcriptional changes in cortical microglia associated with a range of biological processes, including cellular activation, mobility and phagocytosis. Despite the absence of detectable SARS-CoV-2 in the brain at time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.
2021-06-16 | GSE164485 | GEO
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
Project description:In this study, we investigated immune responses in a prospective cohort of hospitalized COVID-19 patients (derivation cohort, DC; n = 126) during the spring of 2020. Plasma samples were collected within four days of admission to measure a panel of innate and complement system immune markers. From a subset of this cohort (n = 80), we performed plasma proteomics and developed a predictive survival model based on proteins differentially expressed between survivors (n = 60) and non-survivors (n = 20). Logistic regression analyses were employed to evaluate the predictive value of these biomarkers for 30-day mortality. The developed proteomic prediction model and the regression analyses were subsequently validated using an independent cohort of hospitalized COVID-19 patients (validation cohort, VC) from the autumn/winter of 2020, who received treatment with remdesivir and dexamethasone.
2025-02-18 | PXD055973 | Pride
Project description:The monoclonal antibody rituximab improves clinical outcome in the treatment of CD20-positive lymphomatous neoplasms, and it is an established drug for treatment of these cancers. Successful mRNA COVID-19 (SARS-CoV-2) vaccination is extremely important for lymphoma patients because they tend to be elderly with comorbidities which leaves them at increased risk of poor outcomes once infected by Coronavirus. Anti-CD20 therapies such as rituximab, deplete B-cell populations and can affect vaccine efficacy. Therefore, a knowledge of the effect of COVID-19 vaccination in this group is critical. We followed a cohort of 28 patients with CD20-positive lymphomatous malignancies treated with rituximab that started prior to their course of COVID-19 vaccination, including boosters. We assayed for vaccine "take" in the humoral (IgG and IgA) and cellular compartment. Here, we show that short-term and long-term development of IgG and IgA antibodies directed toward COVID-19 spike protein are reduced in these patients compared to healthy controls. Conversely, the robustness and breath of underlying T-cell response is equal to healthy controls. This response is not limited to specific parts of the spike protein but spans the spike region, including response to the conserved Receptor Binding Domain (RBD). Our data informs on rational vaccine design and bodes well for future vaccination strategies that require strong induction of T-cell responses in these patients.
| S-EPMC11408186 | biostudies-literature
Project description:Multi-omics single-cell profiling of surface proteins, gene expression and lymphocyte immune receptors from hospitalised COVID-19 patient peripheral blood immune cells and healthy controls donors. Identification of the coordinated immune cell compositional and state changes in response to SARS-CoV-2 infection or LPS challenge, compared to healthy control immune cells.
2021-03-17 | E-MTAB-10026 | biostudies-arrayexpress