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:Single cell transcriptome, TCR and BCR sequencing of FACS-sorted CD45+ cells of the bronchoalveolar lavages of COVID-19 ICU patients
Project description:Single cell transcriptome and BCR sequencing of FACS-sorted activated B cells of the peripheral blood of COVID-19 ICU patients and healthy controls
Project description:Single cell transcriptome and BCR sequencing of FACS-sorted activated B cells of the peripheral blood of COVID-19 ICU patients and healthy controls
Project description:The immune responses to SARS-CoV-2 infections are very complex and remain to be further characterized. In this study, we performed the single-cell B-cell receptor (BCR) sequencing (scBCR-seq) of the PBMC samples from the healthy controls and SARS-CoV-2 infected individuals with various clinical presentations, and subsequently analyzed the abundance, diversity and difference of BCR repertoire in different groups of COVID-19 patients and the healthy controls, respectively. We identified a number of unique heavy or light chain VDJ genes pairs and combinational preference in each group, such as IGKV3-7 enriched in the asymptomatic subjects, whereas IGHV3-23-IGHJ4, IGHV1-18–IGLV3-19, IGHV1-18–IGLV3-21, and IGHV1-1–IGLV3-25 enriched in the recovery patients from the severe diseases. These findings may advance our understanding of the B-cell mediated immune responses to SARS-CoV-2 infections and help develop novel vaccine candidates and therapeutic antibodies against COVID-19.
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:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
Project description:The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T cell response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor Beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to the severity of the disease course. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 785 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 140 SARS-CoV-2 specific TRB sequences belonging to 119 clusters in our COVID-19 patients. Next, we investigated 92 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences towards the nonstructural proteins (NSPs) of ORF1a/b of the SARS-CoV-2 genome was observed in clusters with critical disease course when compared to COVID-19 clusters with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from nonstructural proteins of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
