Longitudinal Single Cell Atlas of COVID-19 Identifies an Early, Transient Prognostic Signature
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PROVIDER: EGAC00001002271 | EGA |
REPOSITORIES: EGA
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Project description:Although the majority of COVID-19 patients are asymptomatic or mildly symptomatic at diagnosis, some will subsequently progress to pneumonia, oxygen desaturation and other symptoms requiring active clinical management. However, molecular markers that identify high-risk patients early in the disease course (Days 1-8 from symptom onset) are scarce, due to the paucity of relevant longitudinal studies. We performed longitudinal single cell RNA-seq on 286 peripheral blood samples from 108 COVID-19 patients, 73 of which had at least one early sample. By examining discrete cell subtypes as well as continuous single cell states, we identified upregulation of type I IFN response genes as the predominant cellular prognostic signature of future disease severity. Type I IFN response was dynamic and complex, spiking early in progressors and then regressing to the cohort mean at the very next sampling, with the cohort mean itself receding to asymptomatic levels by Day 14 regardless of severity. Moreover, in severe and critical cases, IFN response was impaired during Days 5-8, partially due to upregulation of SOCS3 and other negative regulators. We have identified an early prognostic signature for predicting COVID-19 severity as well as potential mechanisms underlying the dysfunctional host immune response in severe disease.
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Project description:In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify early prognostic protein markers and to discover surrogate protein markers that effectively reflect the clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. This study supports the development of protein biomarkers, which might enable better predicting and monitoring progression to severe COVID-19.
2021-09-10 | PXD023686 | Pride
Project description:6 patients with severe COVID-19 were followed longitudinally during hospitalization and up to 1 year after infection, when they also received a vaccine. For each time point and patient, PBMCs were collected and split into 3 pools: 1/3 was sequenced straight; from 1/3 of the samples B cells were enriched (B cell enrichment kit from StemCell) and from 1/3 of the samples, antigen-specific cells were sorted using barcoded N, S and RBD probes. All samples were further stained using a cocktail of 181 barcoded Abs. For all samples we have sequences gene-expression, B cell receptor and Cell surface proteins.
2022-12-06 | E-MTAB-12392 | biostudies-arrayexpress
Project description:A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-12 | GSE209616 | GEO
Project description:There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2 which has infected more than 3 million people worldwide. Approximately 20% of patients with COVID-19 develop severe disease and 5% require intensive care. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines that may be produced by a subset of inflammatory monocytes, lymphopenia, and T cell exhaustion. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from 7 patients hospitalized for COVID-19 and 6 healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19. Sample IDs used in the manuscript were shortened for clarity. They relate to the titles of deposited files as follows: covid_555_1: C1 A covid_555_2: C1 B covid_556: C2 covid_557: C3 covid_558: C4 covid_559: C5 covid_561: C7 HIP002: H1 HIP015: H2 HIP023: H3 HIP043: H4 HIP044: H5 HIP045: H6
2020-05-18 | GSE150728 | GEO
Project description:There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.
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Project description:Acute respiratory distress syndrome (ARDS) results from overwhelming pulmonary inflammation. Prior bulk RNA sequencing provided limited insights into ARDS pathogenesis. We used single cell RNA sequencing to probe ARDS at a higher resolution. PBMCs of patients with pneumonia and sepsis with early ARDS were compared with those of sepsis patients who did not develop ARDS. Monocyte clusters from ARDS patients revealed multiple distinguishing characteristics in comparison with monocytes from patients without ARDS, including downregulation of SOCS3 expression, accompanied by a proinflammatory signature with upregulation of multiple type I IFN-induced genes, especially in CD16+ cells. To generate an ARDS risk score, we identified upregulation of 29 genes in the monocytes of these patients, and 17 showed a similar profile in cells of patients in independent cohorts. Monocytes had increased expression of RAB11A, known to inhibit neutrophil efferocytosis; ATP2B1, a calcium pump that exports Ca2+ implicated in endothelial barrier disruption; and SPARC, associated with processing of procollagen to collagen. These data show that monocytes of ARDS patients upregulate expression of genes not just restricted to those associated with inflammation. Together, our findings identify molecules that are likely involved in ARDS pathogenesis that may inform biomarker and therapeutic development.
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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
Project description:mRNA vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)-based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against SARS-CoV-2 infection in both mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high-resolution single cell analysis, we found that SW0123 vaccination effectively suppressed SARS-CoV-2-induced inflammatory responses by inhibiting the recruitment of pro-inflammatory macrophages and increasing the frequency of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). In addition, the apoptotic process in both lung epithelial and endothelial cells was significantly inhibited, which was proposed to be one major mechanism contributing to vaccine-induced lung protection. Cell-cell interaction in lung compartment was also altered by vaccination. These data collectively unraveled the mechanisms by which the SW0123 protects against lung damage caused by SARS-CoV-2 infection. reduces cardiac function, leading to cardiac remodeling and heart failure. However, the early neonatal mice have a strong ability in cardiomyocyte proliferation and cardiac regeneration after heart damage such as apical resection. Besides of cardiomyocytes, non-myocytes in heart tissue also play important roles in the regeneration process. Previous studies showed that cardiac macrophages, regulatory T cells and CD4+ T cells are all involved in regulating the myocardial regeneration process. However, the roles of other cardiac immune cells in cardiac regeneration remains to be elucidated. B cells is a prominent immune cell in injured heart; here we discovered the indispensable function of cardiac B cells in improving cardiomyocyte proliferation and heart regeneration in neonatal mice.
2022-10-12 | GSE208565 | GEO