In children activation and proliferation level of CX3CR1+ CD8+ T-cells is much higher in multisystem inflammatory syndrome compared to mild COVID-19 14. In adult COVID-19 patients CD8 + T Cell activation status evolves with disease severity in a non-monotonous way 13: effector-like cell clusters expand in mild disease and fall during severe disease with the highest level of T-cell polyfunctionality in moderately ill patients. In addition, studies to date have shown that T cell responses develop in almost all patients with confirmed SARS-CoV-2 infection 12 and remain detectable for several months following infection 8. A large number of unexposed individuals have SARS-CoV-2 reactive CD4+ memory T cells and these memory T cells have been shown to exhibit cross-reactivity against seasonal “common cold” coronavirus strains 8,9 10 11. Whilst it is clear that the adaptive immune response plays an important part in clearance of SARS-CoV-2 infection 5– 7, the exact role of T cells in the resolution or potential exacerbation of SARS-CoV-2 infection is not known 8. This disparity in symptoms is not understood but could represent a difference in the T cell response to SARS-CoV-2. While most children with COVID-19 are asymptomatic or present with mild disease, rare individuals develop severe disease presenting with multisystem hyperinflammatory syndrome (MIS-C) including persistent fever, severe abdominal pain, diarrhoea, myocardial dysfunction, cardiogenic shock, rash and neurological disorders 3, 4. In contrast, children represent a small proportion of COVID-19, comprising less than 2% of cases worldwide 1, 2. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines severity of disease in children.Ĭoronavirus disease 2019, COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high morbidity and mortality in older individuals, and in those with additional comorbidities. ![]() Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. We show that the repertoires of severely ill children are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n=8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. ![]() Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with severe (n=12) or mild (n=8) COVID-19. The reason for variable clinical manifestations is not understood. While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |