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Single-Cell Analysis Reveals the Immune Characteristics of Myeloid Cells and Memory T Cells in Recovered COVID-19 Patients With Different Severities.

ABSTRACT: Despite many studies on the immune characteristics of Coronavirus disease 2019 (COVID-19) patients in the progression stage, a detailed understanding of pertinent immune cells in recovered patients is lacking. We performed single-cell RNA sequencing on samples from recovered COVID-19 patients and healthy controls. We created a comprehensive immune landscape with more than 260,000 peripheral blood mononuclear cells (PBMCs) from 41 samples by integrating our dataset with previously reported datasets, which included samples collected between 27 and 47 days after symptom onset. According to our large-scale single-cell analysis, recovered patients, who had severe symptoms (severe/critical recovered), still exhibited peripheral immune disorders 1-2 months after symptom onset. Specifically, in these severe/critical recovered patients, human leukocyte antigen (HLA) class II and antigen processing pathways were downregulated in both CD14 monocytes and dendritic cells compared to healthy controls, while the proportion of CD14 monocytes increased. These may lead to the downregulation of T-cell differentiation pathways in memory T cells. However, in the mild/moderate recovered patients, the proportion of plasmacytoid dendritic cells increased compared to healthy controls, accompanied by the upregulation of HLA-DRA and HLA-DRB1 in both CD14 monocytes and dendritic cells. In addition, T-cell differentiation regulation and memory T cell-related genes FOS, JUN, CD69, CXCR4, and CD83 were upregulated in the mild/moderate recovered patients. Further, the immunoglobulin heavy chain V3-21 (IGHV3-21) gene segment was preferred in B-cell immune repertoires in severe/critical recovered patients. Collectively, we provide a large-scale single-cell atlas of the peripheral immune response in recovered COVID-19 patients.

SUBMITTER: Li X

PROVIDER: S-EPMC8762286 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status.MethodsData extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID-19 children, were summarized and analyzed.ResultsThe median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)-2, IL-4, IL-6, IL-10, and TNF-α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels.ConclusionPediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID-19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.

Project description:BackgroundAlthough our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complications in COVID-19 infection remains unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection (PASC) with persistent pulmonary symptoms. The dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown.ResultsTo characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing (scRNA-seq) to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from a participant naïve to SARS-CoV-2 (Control) (n=1) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC) (n=2). After integrating scRNA-seq data with a naïve participant from a published dataset, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes, and dendritic cells) was increased in PPASC (n=2) compared to controls (n=2). MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. Further comparison of PPASC with scRNA-seq data with Severe COVID-19 (n=4) data demonstrated enrichment of fibrotic transcriptional signatures. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naïve samples.ConclusionAnalysis of a small scRNA-seq dataset demonstrated alterations in the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests a potential role in PPASC development.

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Single-Cell Analysis Reveals the Immune Characteristics of Myeloid Cells and Memory T Cells in Recovered COVID-19 Patients With Different Severities.

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