Publication date: Jun 01, 2025

Many patients experience long-lasting health problems after COVID-19. The study aimed to assess 3-year trajectories of a comprehensive set of patient-reported outcome measures (PROMs) in patients hospitalized for COVID-19, particularly focusing on the 2- to 3-year trajectory. Additionally, we evaluated prevalence of post-exertional malaise (PEM) at 3 years, its risk factors, co-occurring health problems, and the 3-year trajectories of patients with and without PEM. The CO-FLOW multicentre prospective cohort study followed up adults hospitalized for COVID-19 in 7 hospitals, located in the Netherlands. Study assessments were performed at 3, 6, 12, 24, and 36 months post-discharge, conducted between July 1, 2020, and May 22, 2024. PROMs on recovery, symptoms, fatigue, mental health, cognition, participation, sleep quality, work status, health-related quality of life (HRQoL), and PEM were collected. Generalized estimating equations were used to assess health trajectories and multivariable logistic regression to identify risk factors for PEM. In total, 299/344 (87%) patients completed the 3-year follow-up and were included in the analysis. Complete recovery rates increased (p < 0. 001), from 12% at 3 months to 24% at 3 years. Symptoms of impaired fitness, fatigue, and muscle weakness (all p < 0. 0019) and PROMs for fatigue score, participation, return to work, and HRQoL (all p < 0. 005) improved significantly over time, while PROMs for cognitive failures worsened (p < 0. 001). Between the 2- and 3-year visits, memory problems (OR 1. 4 [1. 1-1. 7], p < 0. 001), and scores of fatigue (MD +1. 0 [0. 4-1. 6], p = 0. 002), cognitive failures (MD +2. 2 [0. 9-3. 4], p < 0. 001), and SF-36 mental component summary (-2. 2 [-3. 1 to -1. 3], p < 0. 001) significantly worsened. At 3 years, 66% of patients experienced fatigue, 63% impaired fitness, 59% memory problems, and 53% concentration problems. PROMs showed that 62% reported poor sleep quality, 55% fatigue, and 28% cognitive failures. PEM was reported by 105/292 (36%) patients at 3 years; risk factors were female sex (OR 3. 4 [95% CI 1. 9-6. 0], p < 0. 001), pre-existing pulmonary disease (3. 0 [1. 7-5. 6], p < 0. 001), physical inactivity pre-COVID-19 (2. 3 [1. 2-4. 1], p = 0. 008), and ICU treatment for COVID-19 (1. 8 [1. 02-3. 0], p = 0. 04). Concurrent fatigue, cognitive failures, and dyspnea were more common in patients with (42%) than without (6%) PEM. Patients with PEM showed poor health outcomes throughout the entire follow-up period, including worsening fatigue and HRQoL during the third year. Many health problems persisted up to 3 years post-discharge, with self-reported fatigue and cognitive problems worsening in the third year. PEM was common, and linked to a more severe phenotype of long COVID. These findings highlight the urgent need to optimize treatment options and investigate underlying pathological mechanisms of COVID-19. The Netherlands Organisation for Health Research and Development (ZonMw); Rijndam Rehabilitation; Laurens.

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