Rewiring the Immune Response in COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Chalmers JD
PROVIDER: S-EPMC7491405 | biostudies-literature |
REPOSITORIES: biostudies-literature
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2021-03-17 | E-MTAB-10026 | biostudies-arrayexpress
Project description:The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.
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Project description:In this prospective observational cohort study, we found transcriptional evidence that persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. COVID-19 patients had an early antiviral response but became indistinguishable on a gene expression level from non-COVID-19 sepsis patients a week later. Early treatment of COVID-19 and non-COVID-19 sepsis ICU patients should focus on pathogen control, but both patient groups also require novel immunomodulatory treatments, particularly later during ICU hospitalization, independent of admission diagnosis. Some T1 samples were uploaded in GSE185263 and were not re-uploaded in this series.
2023-03-24 | GSE222393 | GEO
Project description:Mitochondria are pivotal for bioenergetics, as well as in cellular response to viral infections. Nevertheless, their role in COVID-19 was largely overlooked. Here, we analyzed available bulk RNA-seq datasets from COVID-19 patients and corresponding healthy controls (three blood datasets, N = 48 healthy, 119 patients; two respiratory tract datasets, N = 157 healthy, 524 patients). We found significantly reduced mtDNA gene expression in blood, but not in respiratory tract samples from patients. Next, analysis of eight single-cells RNA-seq datasets from peripheral blood mononuclear cells, nasopharyngeal samples, and Bronchoalveolar lavage fluid (N = 1,192,243 cells), revealed significantly reduced mtDNA gene expression especially in immune system cells from patients. This is associated with elevated expression of nuclear DNA-encoded OXPHOS subunits, suggesting compromised mitochondrial-nuclear co-regulation. This, together with elevated expression of ROS-response genes and glycolysis enzymes in patients, suggest rewiring toward glycolysis, thus generating beneficial conditions for SARS-CoV-2 replication. Our findings underline the centrality of mitochondrial dysfunction in COVID-19.
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Project description:The coronavirus pandemic (COVID-19) is associated with secondary bacterial and fungal infections globally. In India, inappropriate use of glucocorticoids, high prevalence of diabetes mellitus and a conducive environment for fungal growth are considered as the main factors for increased incidence of COVID-19 associated mucormycosis (CAM). Few cases of CAM without steroid abuse and normal blood glucose levels were also reported during the pandemic. This study was designed to explore whether altered immune responses due to severe COVID-19 infection predisposes towards development of mucormycosis. The global transcriptome profiling of monocytes and granulocytic cells derived from CAM, Mucormycosis, COVID-19 and healthy control groups were performed to identify the differentially expressed genes (DEGs) involved in dysregulated host immune response towards respective diseased and healthy conditions.
2024-02-09 | GSE226677 | GEO
Project description:Blood collected from adults pre vaccination and post vaccination to study the immune effects of COVID-19 vaccination and how they relate to antibody and T-cell responses.
2023-01-12 | GSE199750 | GEO
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:BackgroundAlthough the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2.MethodsSamples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively.FindingsComplete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva.InterpretationThe mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route.FundingThis work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).
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Project description:Despite the introduction of vaccines, COVID-19 still affects millions of people worldwide. A better understanding of pathophysiology and the discovery of novel therapies are needed. One of the cells of interest in COVID-19 is the neutrophil. This cell type is being recruited to a site of inflammation as one of the first immune cells. In this project, we investigated a variety of neutrophils phenotypes during COVID-19 by measuring the expression of markers for migration, maturity, activation, gelatinase granules and secondary granules using flow cytometry. We show that neutrophils during COVID-19 exhibit altered phenotypes compared to healthy individuals. The activation level including NETs production and maturity of neutrophils seem to last longer during COVID-19 than expected for innate immunity. Neutrophils as one of the drivers of severe cases of COVID-19 are considered as potential treatment targets. However, for a successful implementation of treatment, there is a need for a better understanding of neutrophil functions and phenotypes in COVID-19. Our study answers some of those questions.
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