Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life

Purpose: Long COVID-19 is a growing public health concern, but its long-term burden and predictors remain underexplored, particularly in underrepresented populations. Methods: This four-year prospective cohort study was conducted in Saudi Arabia, enrolling adults with confirmed acute COVID-19 from multiple affiliated healthcare centers between March 2020 and March 2024. Of 1,521 screened patients, 816 were enrolled and followed for up to four years (median: 24 months). Per WHO criteria, participants were classified as having long COVID-19 (n = 238) or resolved infection (n = 578). Demographics, comorbidities, vaccination, reinfection, and acute illness severity were recorded. Health-related quality of life (HRQoL) was assessed using SF-36 and EQ-5D-5 L. Logistic regression identified predictors of long COVID-19, and Cox proportional hazards models evaluated time to recovery. Results: Fatigue (57.1%), post-exertional malaise (45.8%), cough (41.2%), and cognitive dysfunction (30.7%) were the most common persistent symptoms. Female sex (adjusted OR 11.11; 95% CI: 4.48–26.24) and diabetes mellitus (adjusted OR 14.3; 95% CI: 7.0–29.4) independently predicted long COVID-19. Delayed recovery was associated with female sex (aHR 3.36; 95% CI: 1.85–6.10), diabetes (aHR 1.57; 95% CI: 1.00–2.46), reinfection (aHR 1.86; 95% CI: 1.05–3.29), and hospitalization (aHR 1.08; 95% CI: 1.01–1.16). HRQoL scores remained significantly lower at 6 and 12 months. In the long COVID-19 group, 38.7% of patients normally resumed work within 12 months, compared to 82.3% in the resolved COVID-19 group. Conclusions: Nearly 29% of post-acute COVID-19 patients developed long COVID-19 in this Middle Eastern cohort. Female sex, diabetes, reinfection, and hospitalization predicted delayed recovery. Persistent symptoms and impaired HRQoL highlight the need for early risk stratification and structured post-COVID care.