Gender-based differences in telomere attrition and long-term respiratory dysfunction in COVID-19 ICU survivors one year post-infection: implications for aging-associated pulmonary decline.

A significant proportion of COVID-19 ICU survivors developed long-term respiratory complications at one-year follow-up.

• 73 ICU survivors were included in the study, with 51 men and 22 women.
• At one year, 43.8% of patients reported respiratory symptoms.
• 23.9% of patients developed diffuse parenchymal lung disease (DPLD), assessed via imaging.
• Patients were followed for at least one year post-discharge.

Significant RTL shortening occurred in both men and women who underwent invasive mechanical ventilation (IMV) during their ICU stay.

• Longitudinal analysis showed significant RTL shortening in men who underwent IMV (p=0.011).
• Significant RTL shortening was also observed in women who underwent IMV (p=0.016).
• RTL was quantified from peripheral blood using monochromatic multiplex quantitative PCR (MMqPCR) at hospital admission and one-year post-discharge.

Men who required prone positioning during their ICU stay showed significant RTL shortening at longitudinal analysis.

• RTL shortening in men who needed pronation during their ICU stay was statistically significant (p=0.037).
• This association was specific to men in the longitudinal analysis.
• No equivalent statistically reported finding for RTL shortening associated with pronation was reported for women in the longitudinal analysis.

In women, shorter RTL was associated with persistent respiratory symptoms at one year, particularly among those who required prone positioning.

• Repeated-measures analysis showed an association between shorter RTL and persistent respiratory symptoms in women who needed pronation [adjusted arithmetic mean ratio (aAMR)=0.73, 95%CI=0.60-0.90; p=0.003].
• Women who had undergone pronation and had shorter RTL at follow-up continued to show a higher prevalence of symptoms [aAMR=0.66 (95%CI=0.58-0.76); p<0.001].
• The association between RTL and respiratory symptoms was specific to women in this analysis.

In men, shorter RTL at one-year post-discharge was associated with the presence of diffuse parenchymal lung disease (DPLD).

• Men with shorter RTL at one-year post-discharge had an association with the presence of DPLD [aAMR=0.64 (95%CI=0.50-0.81); p=0.001].
• This association was significant particularly among men who required IMV [aAMR=0.61 (95%CI=0.49-0.76); p<0.001].
• The association was also significant among men who required prone positioning [aAMR=0.56 (95%CI=0.44-0.71); p=0.016].
• DPLD was assessed via imaging.

The association between telomere attrition and long-term pulmonary outcomes was gender-specific, with different outcome types predominating in men versus women.

• In women, shorter RTL was primarily associated with persistent respiratory symptoms, particularly linked to prone positioning.
• In men, shorter RTL was primarily associated with structural lung disease (DPLD), particularly linked to IMV and prone positioning.
• Data were analyzed using gender-stratified generalized linear models, adjusted for clinical covariates.
• The authors describe these findings as underscoring 'the role of telomere attrition as a sex-specific biomarker of aging-associated pulmonary vulnerability.'