Evaluating the Differences between COVID-19 and Post-COVID-19 Syndrome from a Biological Perspective by Examining DNA Breakdownin Young and Older Adults

Introduction: Post-acute COVID-19 syndrome (PACS) has been linked to persistent inflammation and cellular stress; however, biological mechanisms underlying age-related vulnerability, particularly DNA breakdown, remain insufficiently characterized. This study aimed to compare DNA damage in young and older adults during acute COVID-19 and to examine its association with subsequent PACS development. Methods: This longitudinal study included 160 hospitalized COVID-19 patients admitted to Damghan Medical Sciences Hospital during the epidemic phase (late 2019-early 2020). Participants comprised 80 young adults (mean age 29 years; 18-59) and 80 older adults (mean age 67 years; 60-107), with equal sex distribution in both groups. Patients were categorized by disease severity (general ward, non-intubated ICU, intubated ICU). DNA breakdown was assessed using the comet assay during acute infection. Survivors were followed and evaluated for PACS between 2024 and 2025. Results: PACS were developed in 38 young adults (47.5%) and 30 older adults (44.1%). Among younger patients with PACS, 68% were female. DNA breakdown severity increased with acute disease severity in both age groups. Older adults exhibited significantly higher overall DNA damage compared with younger patients, and elevated DNA breakdown was associated with greater PACS symptom burden. Discussion: The findings suggest that persistent DNA instability may represent a biological substrate of PACS, with aging amplifying vulnerability through heightened inflammatory and cellular stress responses. Study limitations include a single-center design and a lack of pre-infection DNA baseline measurements. Conclusion: Age-related susceptibility and inflammation-driven DNA breakdown are key contributors to PACS, underscoring the importance of biological damage assessment in long-term COVID-19 outcomes.