Longitudinal Impact of IL-6 on Cardiovascular Outcomes in COVID-19 Patients: Comparative Analysis During Hospitalization and at Six-Month Follow-Up

Abstract

Background: The COVID-19 pandemic has underscored the interconnection between infectious diseases and cardiovascular health, revealing a significant increase in acute coronary syndrome (ACS) and other cardiovascular complications among those severely affected by the virus. Recent studies have indicated that the systemic inflammation triggered by COVID-19, mainly through cytokines such as interleukin-6 (IL-6), is critical in exacerbating these complications. IL-6 mediates the acute inflammatory response and influences long-term cardiovascular outcomes. Understanding these mechanisms is crucial for managing the long-term health of COVID-19 survivors, especially in regions like Georgia, where cardiovascular diseases are prevalent. Objectives: This study aims to elucidate the predictive role of IL-6 in long-term cardiovascular outcomes post-COVID-19, explicitly focusing on the development of acute coronary syndrome. By comparing IL-6 levels in patients with and without ACS during their hospitalization and following up six months post-recovery, the research seeks to identify patterns that could guide more effective clinical interventions and long-term patient management strategies. Additionally, the study investigates whether elevated IL-6 levels during acute COVID-19 are associated with increased cardiovascular risk, helping to shape targeted approaches for patient care and recovery. Methods: Conducted at the Chapidze Heart Hospital in Tbilisi, Georgia, this retrospective cohort study included 100 RT-PCR-confirmed COVID-19 patients aged 40 to 80. IL-6 levels were measured thrice upon hospitalization, within one week post-hospitalization, and before discharge. Patients were monitored for six months to assess the development of ACS. Statistical analyses included Mann-Whitney U tests for between-group comparisons and repeated measures ANOVA for longitudinal analysis. Results: Our findings indicate significant differences in IL-6 levels between the ACS and non-ACS groups during hospitalization, with elevated levels persistently associated with worse cardiovascular outcomes. Six months post-recovery, patients in the ACS group continued to exhibit higher IL-6 levels, suggesting a sustained inflammatory response. Additionally, ischemic patients demonstrated more severe clinical features, such as more extended hospital stays and higher rates of thrombotic events. Despite these trends, the high variability in IL-6 and other inflammatory markers like ferritin and leukocyte counts underscored the complex nature of their relationship with ACS development. Conclusions: Elevated IL-6 levels during and following hospitalization indicate a higher risk of developing ACS, underscoring the importance of monitoring inflammatory markers for long-term cardiovascular risk assessment. However, the variability in these markers highlights the need for a comprehensive approach to patient evaluation, incorporating multiple biomarkers and clinical data to effectively stratify and manage risk in post-COVID-19 patients. These results emphasize the dynamic interplay of inflammation and cardiovascular disease in COVID-19 recovery and call for further research into targeted interventions to mitigate these risks.