Th1/Th2 immune regulation and functional resilience in older adults following severe COVID-19: a prospective cohort study.

BACKGROUND

Older adults recovering from severe COVID-19 exhibit heterogeneous trajectories, ranging from persistent frailty to full functional recovery. The biological mechanisms underpinning resilience in this population remain poorly defined. This study aimed to investigate the association between Th1/Th2 immune regulation and functional resilience, defined as improvement in frailty status, among older survivors of severe COVID-19.

METHODS

We conducted a prospective study at a tertiary respiratory center in Mexico. Twenty-four patients aged 65 or older with a history of severe COVID-19 were assessed at 4 and 12 months post-discharge. Frailty was evaluated using a validated phenotype adapted for the Mexican population. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to quantify CD4+ T cell subsets, cytokine production (IFN-γ, TNF, and IL-10), and the expression of T-bet, GATA-3, and TIM-3.

RESULTS

Thirteen participants showed improved frailty status over 12 months. Resilient patients exhibited a higher Th1/Th2 (T-bet/GATA-3) ratio at 4 months post-discharge and increased IFN-γ and TNF production at 12 months. TIM-3 expression on CD4+ cells and circulating levels were also elevated in the resilient group.

CONCLUSIONS

A Th1-skewed immune profile early after recovery and sustained proinflammatory cytokine activity are associated with resilience in older adults following severe COVID-19. These findings offer insight into immune mechanisms that may support functional recovery in aging populations.