Association of Acute-Phase IL-6 and SAA with Cardiovascular Events and Mortality Six Years After COVID-19 Infection: An Observational Cohort Study.

Association of Acute-Phase IL-6 and SAA with Cardiovascular Events and Mortality Six Years After COVID-19 Infection: An Observational Cohort Study.

Publication date: May 24, 2026

Coronavirus disease 2019 (COVID-19) has been associated with an increased long-term cardiovascular risk, potentially mediated by magnitude of the acute inflammatory response inflammation. Interleukin-6 (IL-6) and serum amyloid A (SAA) are key components of the inflammatory cascade and may serve as biomarkers of post-COVID cardiovascular vulnerability. This longitudinal observational study investigated the association between post- COVID-19 infection IL-6 and SAA levels and major cardiovascular events over a six-year follow-up period. A total of 97 individuals with documented prior SARS-CoV-2 infection were included. Circulating IL-6 and SAA concentrations were measured in the acute phase. The composite endpoint included incident arrhythmia, myocardial infarction, and all-cause mortality. Biomarker distributions were right-skewed and were therefore analyzed using non-parametric methods and penalized logistic regression models. During follow-up, 14. 4% of participants experienced the composite endpoint. Individuals with adverse outcomes had significantly higher IL-6 and SAA levels compared with event-free participants. IL-6 demonstrated the strongest association with mortality, whereas SAA showed particularly robust associations with the composite endpoint, and with myocardial infarction. Both biomarkers independently predicted long-term adverse events. Circulating IL-6 and SAA concentrations measured during the acute phase of SARS-CoV-2 infection were analyzed in relation to long-term cardiovascular outcomes. These findings support the hypothesis that the magnitude of the acute inflammatory response during SARS-CoV-2 infection may be associated with long-term cardiovascular outcomes and suggest that combined assessment of IL-6 and SAA may have potential utility for hypothesis-generating prognostic signal requiring validation, pending validation in larger studies.

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Concepts Keywords
Biomarker Aged
Coronavirus arrhythmia
Covid Biomarkers
Free Biomarkers
Myocardial Cardiovascular Diseases
cardiovascular risk
COVID-19
COVID-19
Female
Humans
IL6 protein, human
inflammation
Interleukin-6
Interleukin-6
interleukin-6
Longitudinal Studies
Male
Middle Aged
mortality
Myocardial Infarction
myocardial infarction
SARS-CoV-2
SARS-CoV-2
serum amyloid A

Semantics

Type Source Name
disease MESH COVID-19
disease MESH Infection
disease MESH inflammation
pathway REACTOME SARS-CoV-2 Infection
disease MESH included
disease MESH arrhythmia
disease MESH myocardial infarction
drug DRUGBANK Coenzyme M
disease MESH severe acute respiratory syndrome
disease MESH cytokine storm
disease MESH respiratory failure
disease MESH atherosclerosis
disease MESH thrombosis
disease MESH heart failure
disease MESH death
disease MESH injury
disease MESH cardiovascular disease
drug DRUGBANK Canakinumab
disease MESH ischemic heart disease
drug DRUGBANK Angiotensin II
disease MESH hypertension
disease MESH diabetes mellitus

Original Article

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