tetano
Editor, Senior Moderator
Immun Ageing
. 2024 Mar 8;21(1):17.
doi: 10.1186/s12979-024-00423-6. Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients
Mailton Prestes Madruga[SUP] #[/SUP][SUP] 1 [/SUP], Lucas Kich Grun[SUP] #[/SUP][SUP] 1 [/SUP], Letícya Simone Melo Dos Santos[SUP] 1 [/SUP], Frederico Orlando Friedrich[SUP] 2 [/SUP], Douglas Bitencourt Antunes[SUP] 1 [/SUP], Marcella Elesbão Fogaça Rocha[SUP] 1 [/SUP], Pedro Luis Silva[SUP] 1 [/SUP], Gilson P Dorneles[SUP] 3 [/SUP], Paula Coelho Teixeira[SUP] 3 [/SUP], Tiago Franco Oliveira[SUP] 3 [/SUP], Pedro R T Romão[SUP] 3 [/SUP], Lucas Santos[SUP] 4 [/SUP], José Claudio Fonseca Moreira[SUP] 4 [/SUP], Vinicius Schenk Michaelsen[SUP] 5 [/SUP], Marcelo Cypel[SUP] 6 [/SUP], Marcos Otávio Brum Antunes[SUP] 2 [/SUP], Marcus Herbert Jones[SUP] 2 [/SUP], Florencia María Barbé-Tuana[SUP] #[/SUP][SUP] 1 [/SUP], Moisés Evandro Bauer[SUP] #[/SUP][SUP] 7 [/SUP]
Affiliations
Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight.
Results: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56[SUP]+[/SUP]CD16[SUP]-[/SUP]) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56[SUP]+[/SUP]CD16[SUP]+[/SUP]), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4[SUP]+[/SUP]CD38[SUP]+[/SUP] cells than controls. Contrasting changes were reported in CD25[SUP]+[/SUP]CD127[SUP]low/neg[/SUP] regulatory T cells, with increased and decreased proportions found in CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP]) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8[SUP]+[/SUP]CD57[SUP]+[/SUP]NKG2A[SUP]+[/SUP] cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19.
Conclusions: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.
Keywords: Ageing; Inflammation; Microbial translocation; Obesity; SARS-CoV-2; T cells.
. 2024 Mar 8;21(1):17.
doi: 10.1186/s12979-024-00423-6. Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients
Mailton Prestes Madruga[SUP] #[/SUP][SUP] 1 [/SUP], Lucas Kich Grun[SUP] #[/SUP][SUP] 1 [/SUP], Letícya Simone Melo Dos Santos[SUP] 1 [/SUP], Frederico Orlando Friedrich[SUP] 2 [/SUP], Douglas Bitencourt Antunes[SUP] 1 [/SUP], Marcella Elesbão Fogaça Rocha[SUP] 1 [/SUP], Pedro Luis Silva[SUP] 1 [/SUP], Gilson P Dorneles[SUP] 3 [/SUP], Paula Coelho Teixeira[SUP] 3 [/SUP], Tiago Franco Oliveira[SUP] 3 [/SUP], Pedro R T Romão[SUP] 3 [/SUP], Lucas Santos[SUP] 4 [/SUP], José Claudio Fonseca Moreira[SUP] 4 [/SUP], Vinicius Schenk Michaelsen[SUP] 5 [/SUP], Marcelo Cypel[SUP] 6 [/SUP], Marcos Otávio Brum Antunes[SUP] 2 [/SUP], Marcus Herbert Jones[SUP] 2 [/SUP], Florencia María Barbé-Tuana[SUP] #[/SUP][SUP] 1 [/SUP], Moisés Evandro Bauer[SUP] #[/SUP][SUP] 7 [/SUP]
Affiliations
- PMID: 38454515
- PMCID: PMC10921685
- DOI: 10.1186/s12979-024-00423-6
Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight.
Results: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56[SUP]+[/SUP]CD16[SUP]-[/SUP]) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56[SUP]+[/SUP]CD16[SUP]+[/SUP]), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4[SUP]+[/SUP]CD38[SUP]+[/SUP] cells than controls. Contrasting changes were reported in CD25[SUP]+[/SUP]CD127[SUP]low/neg[/SUP] regulatory T cells, with increased and decreased proportions found in CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP]) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8[SUP]+[/SUP]CD57[SUP]+[/SUP]NKG2A[SUP]+[/SUP] cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19.
Conclusions: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.
Keywords: Ageing; Inflammation; Microbial translocation; Obesity; SARS-CoV-2; T cells.