Summary: 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.
Overall Design: single-cell RNA-seq / TCR-seq assay of PBMC or BAL T cells from aged COVID-19 convalescents or healthy donors
Strategy: |
|
Species: |
|
Healthy Condition: |
|
Cell Type: |
|
Growth Protocol: | - |
Treatment Protocol: | CD3+ T cells were purified from PBMC and BAL cells with the StraightFrom® Whole Blood CD3 MicroBeads (Miltenyi Biotech). |
Extract Protocol: | Library were generated by following the instruction of 10X 5’ Library & Gel Bead Kit v1.1 |
Library Construction Protocol: | Library were generated by following the instruction of 10X 5’ Library & Gel Bead Kit v1.1 |
Molecule Type: | polyA(+) RNA |
Library Source: | |
Library Layout: | PAIRED |
Library Strand: | - |
Platform: | ILLUMINA |
Instrument Model: | Illumina HiSeq 4000 |
Strand-Specific: | - |
Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
---|