Introduction Long COVID is a heterogeneous chronic condition with symptoms that often overlap with other infection-associated chronic conditions (IACC). These clinical similarities highlight gaps in healthcare education and delivery, leaving many primary care clinicians unprepared to manage these conditions. To address this need, we conducted a two-arm, single-blind, cluster randomized controlled trial (Clinicaltrials.gov ID NCT05167227) in an under-resourced Federally Qualified Health Center primary care setting to evaluate the effectiveness of the Long COVID and Fatiguing Illness Recovery Program in improving patient outcomes with long COVID, myalgic encephalomyelitis/chronic fatigue syndrome, and other IACCs. Methods From December 2021 through October 2023, 20 primary care clinicians were randomized in a 1:1 ratio. The intervention arm participated in weekly multidisciplinary Extension for Community Healthcare Outcomes (ECHO) case-based virtual community of practice sessions, monthly webinars, and quarterly short courses. The control arm participated in monthly webinars and quarterly short courses. A total of 590 patients were assigned to participating clinicians and completed surveys including Patient-Reported Outcomes Measurement Information System (PROMIS)-29 at baseline, 3-, 6-, 9-, and 12-months. Patient-reported outcomes from 298 control and 289 intervention patients completed surveys were analyzed using statistical tests and linear mixed-effects regression to examine between-arm differences and longitudinal treatment effects. Results Both arms showed improvements over 12 months on multiple PROMIS scales including Fatigue, Physical Function, Pain Interference, Social Roles, Dyspnea, and Applied Cognition, approaching reference population norms at study end. A statistically significant difference was observed on pain interference, with the intervention arm having better outcomes than control at 12 months [mean (SD): 57 (11) vs. 60 (10), P = 0.009]. Longitudinal analyses revealed a significant treatment effect on pain interference [estimate = –1.95; 95% CI (–3.79, −0.10); P = 0.04] and a higher proportion of intervention patients achieved clinically meaningful improvements (≥5T-score points) compared with controls (43% vs. 29%; P = 0.01). Discussion The ECHO case-based virtual community of practice model showed evidence that clinician-focused education may enhance primary care management of patients with complex fatiguing illnesses, supporting the model's value in under-resourced settings. Clinical Trial Registration : https://clinicaltrial.gov/ , identifier NCT05167227.
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