Longitudinal Assessment of DNA Damage in PBMCs From Hospitalized COVID-19 Patients via Alkaline Comet Assay

Growing evidence suggests an association between SARS-CoV-2 infection and oxidative stress-related genomic damage, primarily from cross-sectional studies. However, longitudinal evaluations remain limited. Here, we assessed DNA damage in peripheral blood mononuclear cells (PBMCs) from hospitalized COVID-19 patients during the first days of hospitalization, using the alkaline comet assay. A longitudinal descriptive study was conducted at a modular COVID-19 hospital in Lima, Peru, throughout October 2020. Blood samples were collected at admission (day 0), day 3, and day 6. DNA damage was assessed by measuring tail length, tail moment, and tail intensity, which were modeled using mixed-effects linear models. Concurrent hematological parameters and acute-phase proteins were also analyzed to characterize their time-course patterns in conjunction with DNA damage. Results from the adjusted mixed-effects model showed a significant temporal increase in DNA damage parameters, particularly tail intensity (β = 0.25 per day, p = 0.003), relative to baseline measurements, with a peak observed on day 3 of hospitalization. These changes aligned with variations in platelet counts and transferrin levels, while lymphocyte and monocyte counts, along with C-reactive protein, showed an inverse trend, reflecting the dynamic interplay of the inflammatory response and DNA damage. No significant differences in comet assay parameters were observed between survivors and non-survivors, likely due to the limited and unbalanced sample. The findings indicate the presence of a measurable DNA damage burden in PBMCs of hospitalized COVID-19 patients, highlighting the need to further studies to clarify the mechanisms underlying DNA damage and its potential long-term biological implications.