tetano
Editor, Senior Moderator
Sci Rep
. 2025 Aug 19;15(1):30388.
doi: 10.1038/s41598-025-11714-3. Reduced IFN-γ-expressing SARS-CoV-2 specific CD4[SUP]+[/SUP] T cells and transient CD8 [SUP]+[/SUP] T cell activation associate with higher HOMA-IR 1-year post COVID-19 in obese individuals
Rona Kartika[SUP] 1 2 [/SUP], Dicky Levenus Tahapary[SUP] 2 3 [/SUP], Farid Kurniawan[SUP] 2 3 [/SUP], Syahidatul Wafa[SUP] 2 3 [/SUP], Tika Pradnjaparamita[SUP] 2 [/SUP], Simon P Jochems[SUP] 4 [/SUP], Heri Wibowo[SUP] 5 6 [/SUP], Imam Subekti[SUP] 7 [/SUP]
Affiliations
Insulin resistance is one of the metabolic complications of COVID-19. Our previous study showed a 22% median increase in homeostasis model assessment-estimated insulin resistance (HOMA-IR) in obese individuals at 12 months post-infection compared to acute infection. This study aimed to investigate the association between various subsets of IFN-γ-expressing SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP] +[/SUP] T cells and insulin resistance in convalescent COVID-19 patients over a one-year post-infection follow-up period. A nested case control study of 47 COVID-19 patients was followed for 12 months post-infection and categorized into three groups based on obesity and changes in HOMA-IR at one year: non-obese without increased HOMA-IR (NO), obese without increased HOMA-IR (O), and obese with increased HOMA-IR (O-IR). Increased HOMA-IR was defined as a HOMA-IR ratio (12-month to 1-month convalescence phase) > 1.21. To study antigen-specific responses, peripheral blood mononuclear cells (PBMC)s were isolated and incubated with SARS-CoV-2 peptide antigens for 24 h. Intracellular IFN-γ expression, as well as exhaustion and senescence markers, in various CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell subsets were measured by flow cytometry. The abundance of IFN-γ-expressing SARS-CoV-2-specific CD4[SUP]+[/SUP] T cells was lower in the O-IR group compared to individuals without increased HOMA-IR during the 9th to 12th months of follow-up (p < 0.05). Conversely, the O-IR group exhibited a mild but significantly higher IFN-γ-expressing CD8[SUP]+[/SUP] T cells from the 3rd to the 9th month of the convalescence phase (p < 0.05). A reduced proportion of functional (PD-1[SUP]-[/SUP]CD57[SUP]-[/SUP]) SARS-CoV-2-specific T cells was observed in O-IR group. Furthermore, the reduced proportion of functional SARS-CoV-2-specific CD4⁺ T cells observed within 12 months of convalescence were have significant weak negative correlation with HOMA-IR ratio as well as HOMA-IR value. Our study demonstrates that obese individuals with increased HOMA-IR exhibited a reduced proportion of IFN-γ-expressing functional SARS-CoV-2-specific CD4⁺ T cells one year after COVID-19. This reduction, along with the decreased frequencies of both functional CD4⁺ within 12 months of convalescence, suggests a potential association between impaired SARS-CoV-2-specific T cell function and the development of insulin resistance following COVID-19. These findings warrant further investigation.
Keywords: COVID-19; Exhaustion; Insulin resistance; Senescent; T cells.
. 2025 Aug 19;15(1):30388.
doi: 10.1038/s41598-025-11714-3. Reduced IFN-γ-expressing SARS-CoV-2 specific CD4[SUP]+[/SUP] T cells and transient CD8 [SUP]+[/SUP] T cell activation associate with higher HOMA-IR 1-year post COVID-19 in obese individuals
Rona Kartika[SUP] 1 2 [/SUP], Dicky Levenus Tahapary[SUP] 2 3 [/SUP], Farid Kurniawan[SUP] 2 3 [/SUP], Syahidatul Wafa[SUP] 2 3 [/SUP], Tika Pradnjaparamita[SUP] 2 [/SUP], Simon P Jochems[SUP] 4 [/SUP], Heri Wibowo[SUP] 5 6 [/SUP], Imam Subekti[SUP] 7 [/SUP]
Affiliations
- PMID: 40830616
- PMCID: PMC12365270
- DOI: 10.1038/s41598-025-11714-3
Insulin resistance is one of the metabolic complications of COVID-19. Our previous study showed a 22% median increase in homeostasis model assessment-estimated insulin resistance (HOMA-IR) in obese individuals at 12 months post-infection compared to acute infection. This study aimed to investigate the association between various subsets of IFN-γ-expressing SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP] +[/SUP] T cells and insulin resistance in convalescent COVID-19 patients over a one-year post-infection follow-up period. A nested case control study of 47 COVID-19 patients was followed for 12 months post-infection and categorized into three groups based on obesity and changes in HOMA-IR at one year: non-obese without increased HOMA-IR (NO), obese without increased HOMA-IR (O), and obese with increased HOMA-IR (O-IR). Increased HOMA-IR was defined as a HOMA-IR ratio (12-month to 1-month convalescence phase) > 1.21. To study antigen-specific responses, peripheral blood mononuclear cells (PBMC)s were isolated and incubated with SARS-CoV-2 peptide antigens for 24 h. Intracellular IFN-γ expression, as well as exhaustion and senescence markers, in various CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell subsets were measured by flow cytometry. The abundance of IFN-γ-expressing SARS-CoV-2-specific CD4[SUP]+[/SUP] T cells was lower in the O-IR group compared to individuals without increased HOMA-IR during the 9th to 12th months of follow-up (p < 0.05). Conversely, the O-IR group exhibited a mild but significantly higher IFN-γ-expressing CD8[SUP]+[/SUP] T cells from the 3rd to the 9th month of the convalescence phase (p < 0.05). A reduced proportion of functional (PD-1[SUP]-[/SUP]CD57[SUP]-[/SUP]) SARS-CoV-2-specific T cells was observed in O-IR group. Furthermore, the reduced proportion of functional SARS-CoV-2-specific CD4⁺ T cells observed within 12 months of convalescence were have significant weak negative correlation with HOMA-IR ratio as well as HOMA-IR value. Our study demonstrates that obese individuals with increased HOMA-IR exhibited a reduced proportion of IFN-γ-expressing functional SARS-CoV-2-specific CD4⁺ T cells one year after COVID-19. This reduction, along with the decreased frequencies of both functional CD4⁺ within 12 months of convalescence, suggests a potential association between impaired SARS-CoV-2-specific T cell function and the development of insulin resistance following COVID-19. These findings warrant further investigation.
Keywords: COVID-19; Exhaustion; Insulin resistance; Senescent; T cells.