Abstract: Introduction: Long COVID, or Post-Acute Sequelae of SARS-CoV-2 (PASC), is a multi-systemic disorder affecting a substantial proportion of COVID-19 survivors. The angiotensin-converting enzyme 2 (ACE2) receptor, the primary entry point for SARS-CoV-2, is highly expressed in reproductive tissues, suggesting a potential direct impact on female reproductive health. Data on this association, particularly from diverse ethnic populations like those in North-East India, is scarce.
Objectives: To conduct a prospective, matched cohort study investigating the effects of Long COVID on menstrual cycle regularity, biomarkers of ovarian reserve, and clinical pregnancy outcomes in a population of women from North-East India.
Methods: A total of 316 women (18-45 years) with confirmed prior SARS-CoV-2 infection were recruited from three tertiary-care centres across North-East India. Participants were stratified into two cohorts: a Long COVID group (n=158) and a matched control group of post-COVID individuals without Long COVID symptoms (n=158). Matching was based on age (±2 years), body mass index (BMI ±2 kg/m²), and parity. Comprehensive assessment included structured interviews for menstrual history, biochemical analysis of serum Anti-Müllerian Hormone (AMH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), prolactin, and thyroid-stimulating hormone (TSH), and prospective follow-up of pregnancy outcomes over 12 months.
Results: The prevalence of menstrual irregularities was significantly higher in the Long COVID cohort compared to controls (55.1% vs. 28.5%; adjusted odds ratio [aOR] 3.12, 95% CI 1.95-4.98, p<0.001). Women with Long COVID exhibited statistically significant lower median AMH levels (2.1 ng/mL [IQR: 1.4-3.0] vs. 2.8 ng/mL [IQR: 1.9-3.6]; p=0.01). The cumulative incidence of pregnancy at 12 months was lower in the Long COVID group (62% vs. 78%; Hazard Ratio 0.65, 95% CI 0.48-0.89, p=0.02). Pregnancies in the Long COVID cohort were associated with higher rates of preterm birth (17.8% vs. 6.9%; p=0.03) and gestational hypertension (15.6% vs. 5.2%; p=0.04).
Conclusions: This study provides compelling evidence from a unique ethnic population that Long COVID is significantly associated with menstrual dysfunction, diminished ovarian reserve as indicated by reduced AMH, reduced fecundability, and an elevated risk of adverse obstetric outcomes. These findings necessitate increased clinical vigilance and dedicated reproductive health counselling for women recovering from COVID-19.
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