Predictors of post-COVID syndrome: opposing effects of arterial stiffness and targeted therapy in acute COVID-19

Aim. To evaluate the impact of arterial stiffness and targeted therapy (biologic drugs and Janus kinase inhibitor) during the acute phase of coronavirus disease 2019 (COVID-19) on the risk of post-COVID syndrome (PCS). The rationale for the study is the high prevalence of PCS and the insufficient knowledge of factors influencing its development, especially in the context of using modern biologic drugs.

Material and methods. The prospective observational study included 129 adult patients (55% women) hospitalised with a confirmed diagnosis of COVID-19. The mean age was 59.16±13.38 years. Upon admission, all participants underwent measurement of the cardio-ankle vascular index (CAVI) to assess arterial stiffness. Data on the acute course of illness and clinical status during the 6-month follow-up after discharge were obtained from electronic medical records. PCS was diagnosed according to WHO criteria. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of PCS, with odds ratios (ORs) and 95% confidence intervals (CI) calculated. Results. PCS was diagnosed in 33.3% of patients. The most common PCS symptoms were fatigue (20.2%), headache (10.9%), shortness of breath (10.1%), palpitations (9.3%), and dizziness (8.5%). Univariate analysis revealed significant association with PCS development for age, arterial hypertension (AH), level of systolic blood pressure (SBP) at admission, elevated CAVI index (≥ 9.5), and glomerular filtration rate (GFR). The multivariate regression model confirmed the independent status of three predictors: elevated CAVI index (OR 3.533; 95% CI 1.242-10.047; p=0.018) and SBP level at hospitalization (OR 1.053; 95% CI 1.016-1.091; p=0.004) were associated with an increased risk of PCS. At the same time, the use of targeted drugs (levilimab, olokizumab, baricitinib) during the acute phase of COVID-19 significantly reduced the likelihood of developing PCS (OR 0.276; 95% CI 0.104-0.734; p=0.010), which corresponds to a 3.62-fold reduction in odds.

Conclusion. Increased arterial stiffness (CAVI ≥9.5) and elevated systolic blood pressure at hospitalisation are independent predictors of PCS, supporting a key role of vascular dysfunction in its pathogenesis. Targeted therapy administered during the acute phase of COVID-19 was associated with a protective effect against PCS, possibly through attenuation of cytokine-driven inflammation and prevention of prolonged endothelial injury. These findings support the potential value of targeted therapy not only for improving acute COVID-19 outcomes but also for reducing long-term adverse outcome, and underscore the importance of monitoring and managing vascular risk factors in COVID-19 survivors.

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