Complement activation induces excessive T cell cytotoxicity in severe COVID-19
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA732416 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We performed single cell transcriptomics in 13 acute and convalescent mild versus severe COVID-19 subjects, in healthy controls and in sujects with flu-like-illness and HBV infection to assess COVID-19-specific T cell populations und function.
2021-06-08 | GSE175450 | GEO
Project description: Not available
| S-EPMC8712270 | biostudies-literature
Project description:The SARS-CoV-2 infection elicits widespread immunological reactions and causes severe diseases in some individuals. However, the molecular basis behind the excessive, yet non-productive immune response in COVID-19 patients with severe diseases is not fully understood. Nor is it fully known of the molecular and cellular discrepancies between severe COVID-19 and sepsis caused by other infections. To gain systems-level insights into the pathogenesis of COVID-19, we compared the blood proteome and phosphoproteome of patients under intensive care with or without SARS-CoV-2 infection, and healthy control subjects by quantitative mass spectrometry. SARS-CoV-2 infection causes global reprogramming of the kinome and the phosphoproteome, resulting in incomplete adaptive immune responses mediated by B cells and T cells, compromised innate immune response via inhibitory SIGLEC and SLAM family receptor signaling, and excessive JAK/STAT signaling. Our work identifies the kinases CK2, SYK, JAK2/3, TYK2, and the cytokine IL-12 as potential targets for the immunomodulatory treatment of severe COVID-19 and provides a valuable resource for deciphering the mechanism of pathogen-host interactions.
2024-05-24 | PXD024087 | Pride
Project description:Manuscript describes the daily dynamics of transcriptional responses in whole blood, from acute to convalescent phase, in severe and non-severe COVID-19 patients.
2020-12-31 | E-MTAB-9721 | biostudies-arrayexpress
Project description:Although most SARS-CoV-2-infected individuals experience mild COVID-19, some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly upregulation of the TNF/IL-1beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1beta-driven inflammation, and this was not seen in patients with milder COVID-19 infection. Based on this, we propose that the type I IFN response exacerbates inflammation in patients with severe COVID-19 infection.
2020-07-06 | GSE149689 | GEO
Project description:The study aims at investigating the specifical transcriptional signatures of severe COVID-19
2021-01-15 | GSE164805 | GEO
Project description:In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -a CD80/86 costimulation inhibitor- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoVinfected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.
2020-07-01 | GSE151161 | GEO
Project description:Pre-existing memory T-cells against SARS-CoV-2 are present in a fraction of unexposed individuals and their induction by common cold corona viruses (CCCoVs) infection is suggested. Here we demonstrate that SARS-CoV-2-reactive T-cells were present in the memory compartment of virtually all unexposed individuals but possessed only low functional avidity. They harbored multiple, highly variable cross-reactivities that were not restricted to CCCoVs. Cross-reactivity to CCCoV was almost absent in COVID-19 patients. This was irrespective of strong T-cell memory against CCCoV in all donors. In severe but not mild COVID-19, SARS-CoV-2-specific T-cells also displayed low functional avidity and reduced clonal expansion, despite strongly increased frequencies. Our data question a major protective role of CCCoV for COVID-19. Instead, we suggest that a low avidity pre-existing T-cell memory may contribute to the excessive but low avidity T-cell responses, which we identified here as a hallmark of severe COVID-19.
2020-12-23 | GSE162086 | GEO
Project description:In order to identify differentially abundant proteins, human plasma samples from COVID-19 patients with either a mild or moderate (MM) or a critical or severe (CS) disease course from acute phase of infection were analyzed on antibody microarrays 998 different proteins by 1,425 antibodies.
2023-03-15 | E-MTAB-12777 | biostudies-arrayexpress
Project description:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
2021-10-05 | GSE157789 | GEO