Title : Association of menopause and long COVID symptoms on vascular outcomes: AMLOV study
Abstract:
Introduction: Sex differences have been observed in both the incidence and symptom burden of long COVID (LC), with women demonstrating a higher incidence than men (8.5% vs. 5.2%) and greater symptom burden (4.4% vs. 2.3%). Menopause is marked by declining estrogen levels, increased proinflammatory cytokines, and heightened immune activation. Estrogen deficiency can arise from menopause or LC and promotes systemic inflammation, which overlaps with inflammatory pathways implicated in LC. This suggests that LC may amplify or unmask menopause-related immune dysregulation. It is unclear whether viral persistence or sustained immune activation influences hormonal dynamics. Understanding this relationship is clinically important as both LC and menopause are independently associated with increased cardiovascular risk, including myocardial infarction, heart failure, arrhythmias, thrombotic events, and stroke, with menopause alone increasing cardiovascular risk factors by approximately 18%.
Significance: Despite strong mechanistic plausibility and population-level relevance, no studies have examined LC symptoms as a modifier of vascular events in menopausal-aged women.
Methods: We investigated the association of LC symptom burden in menopausal aged women with and without menopause and with and without LC and investigated the cardiovascular and stroke outcomes. Long Covid (LC) is defined as a post-acute sequelae of SARS-CoV-2 (PASC) score of >11, a patient-reported outcome measure, indicating a high multi-symptom burden. Utilizing the Researching COVID to Enhance Recovery (RECOVER) adult cohort database. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with logistic regression to evaluate associations between long COVID and stroke and cardiovascular outcomes, stratified by menopausal status.
Results: We identified 2,345 biological female participants aged 40-56. 1,194 without menopause (age 40-56) with and without LC, and 1,151 with menopause (age 40-56) with and without LC. We found increased odds of cardiovascular events and strokes in women with Long COVID who were not in menopause.
Conclusion: LC was associated with significantly increased odds of cardiovascular disease and stroke, regardless of menopausal status. No significant associations were observed among never-infected groups. As next steps, we will investigate whether estrogen deficiency, specifically the distinction between acute and sustained deficiency, is the primary driver of inflammatory pathways that contribute to increased cardiovascular and stroke risk in women with LC.
