Project description:Purpose: To understand the single cell transcriptional and epigenetic landscape of immune cells from infants and young children infected with COVID-19
Project description:Although a substantial proportion of severe COVID-19 pneumonia survivors exhibit long-term pulmonary sequalae, the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. In this cohort of aged COVID-19 convalescents, chronic lung impairment was accompanied by persistent systemic inflammation and respiratory immune alterations. Detailed evaluation of the lung immune compartment revealed dysregulated respiratory CD8+ T cell responses that likely underlie the impaired lung function following acute COVID-19 during aging. Single cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells causing persistent tissue conditions following COVID-19. Our results have revealed key pathophysiological and immune traits that support the development of lung sequelae following SARS-CoV2 pneumonia during aging, with implications for the treatment of chronic COVID-19 symptoms.
Project description:This study utilizes multi-omic biological data to perform deep immunophenotyping on the major immune cell classes in COVID-19 patients. 10X Genomics Chromium Single Cell Kits were used with Biolegend TotalSeq-C human antibodies to gather single-cell transcriptomic, surface protein, and TCR/BCR sequence information from 254 COVID-19 blood draws (a draw near diagnosis (-BL) and a draw a few days later (-AC)) and 16 healthy donors.
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.
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.
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.
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.
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
Project description:Immune characteristics associated with Coronavirus Disease-2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid (BALF) immune cells from patients with varying severity of COVID-19 disease and from healthy subjects using single-cell RNA-sequencing. Proinflammatory monocyte-derived macrophages were abundant in the BALF from severe COVID-9 patients. Moderate cases were characterized by the presence of highly clonally expanded tissue-resident CD8+ T cells. This atlas of the bronchoalveolar immune-microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.