T Cell Immunity, Ageing, and COVID-19 Severity

1 Autaa et al. 2025 β€” Aging and IL-18-Driven Inflammation Limit SARS-CoV-2-Specific CD8+ T Cell Responses

Full Citation:: Autaa G, Papagno L, Nogimori T, et al. Aging and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19. JCI Insight. 2025;10(4):e180867. (Autaa et al. 2025) DOI:: 10.1172/jci.insight.180867 PMID:: 39847442 / PMCID: PMC11949069 Study Design:: Prospective cohort; French and Japanese patients from pandemic initial wave; cross-sectional immune profiling Key Findings::

- Age-related contraction of the naive lymphocyte pool impairs SARS-CoV-2-specific CD8^+^ T cell induction (more affected than CD4^+^ or antibody responses)
- IL-18, elevated in severe disease, specifically suppresses both new and recall antigen-specific CD8^+^ T cell responses
- Antibody responses to spike protein showed no age-related decline β€” CD8 impairment is specifically cellular
- Provides mechanistic explanation for older adults' disproportionate vulnerability to severe and prolonged COVID

Relevance:: Relevant to ME/CFS T cell exhaustion and age-related immune dysregulation. If IL-18 (elevated in severe COVID) suppresses CD8+ T cell induction, this could explain persistent viral reservoirs in older ME/CFS patients with reduced CD8 surveillance. The IL-18-CD8 suppression axis also connects to the NETosis-NLRP3-IL-18 loop documented in Long COVID/ME/CFS immune studies. Certainty Assessment::

- *Quality:* High (JCI Insight; multi-centre French-Japanese cohort)
- *Sample:* Multi-centre cohort; pandemic initial wave
- *Replication:* Consistent with multiple independent COVID-19 immune senescence studies
- *Certainty:* 0.70
- *Limitation:* Acute COVID-19 cohort β€” long COVID or ME/CFS populations not directly examined

References

Autaa, GaΓ«lle, Laura Papagno, Takuto Nogimori, Andrea Boizard-Moracchini, Daniil Korenkov, Maeva Roy, Koichiro Suzuki, et al. 2025. β€œAging and Inflammation Limit the Induction of SARS-CoV-2-Specific CD8\(^+\) T Cell Responses in Severe COVID-19.” JCI Insight 10 (4): e180867. https://doi.org/10.1172/jci.insight.180867.