Longitudinal trajectories of hematological indices and serum metalloproteinases-2 and 9 over 1 year after moderate and severe COVID-19

Introduction: The long-term clinical burden of Coronavirus disease (COVID-19) remains substantial, yet one-year cohort evidence linking blood-based biomarkers to persistent sequelae is limited. Methods: We conducted a longitudinal study in adults aged 18-80 years who were classified as moderate or severe COVID-19 or non-COVID-19 controls. Blood was collected at four time points through 360 days after infection or hospital discharge. Cytokines were quantified by flow cytometry. MMP-2 and MMP-9 levels and activity were assessed by gelatin zymography. Hematological parameters were measured in an accredited clinical laboratory. Longitudinal effects were evaluated using generalized estimating equations. Results: Compared with moderate cases and controls, participants who experienced severe acute disease showed persistent immune dysregulation and systemic inflammation at approximately 1 year, with higher concentrations of inflammatory mediators and cytokines and sustained elevations in MMP-2 and MMP-9. Complete blood count-derived indices were also altered over time in severe cases, including the aggregate index of systemic inflammation, the C-reactive protein to lymphocyte ratio, the neutrophil to platelet ratio, and the systemic inflammation response index, together with red cell distribution width, while renal function tests, hepatic enzymes, and muscle injury markers were largely stable across groups. Discussion: These findings delineate a persistent inflammatory and matrix-remodeling signature up to 1 year after severe COVID-19, based on longitudinal biomarker profiles rather than symptom-defined long COVID-19 outcomes. This biomarker panel may help to inform future studies of post-acute risk stratification and targeted interventions, but prospective prognostic validation and clinical endpoint data are still required. Clinical trial registration: https://clinicaltrials.gov/study/NCT04961255?term=NCT04961255&rank=1, NCT04961255.