Efficacy of a psychotherapeutic group intervention for patients with Post-COVID-19 condition: a randomized controlled trial (PsyLoCo study)

BACKGROUND: Persistent physical symptoms such as fatigue following SARS-CoV-2 infection are common and often accompanied by cognitive complaints. Alongside biological mechanisms, psychosocial processes can contribute to symptom persistence. Psychotherapeutic interventions could be beneficial in symptom reduction. However, evidence of group-based psychotherapies tailored to Post-COVID-19 condition (PCS) remains limited. METHODS: In this randomized waitlist-controlled crossover study in an outpatient psychosomatic setting, adults with prior SARS-CoV-2 infection and persisting functionally impairing symptoms were randomized to immediate group psychotherapeutic treatment (intervention group, IG) or treatment as usual with delayed group treatment (control/waitlist group, CG). The intervention comprised 10 bi-weekly manual-guided group sessions (50 min) covering psychoeducation, somatic symptom processing, emotional regulation, and social reintegration. Primary outcome was somatic symptom burden (SSS-8). Secondary outcomes were depressive symptoms (PHQ-9) and anxiety symptoms (GAD-7). Childhood maltreatment (CTS) was examined as a moderator. Efficacy in the randomized phase was tested using ANCOVA comparing post-treatment outcomes in the IG with post-waiting outcomes in the CG, adjusted for baseline severity. Three-month follow-up assessments were analyzed descriptively and exploratorily. TRIAL REGISTRATION: https://osf.io/tdn38/overview on Feb 13, 2024 and German Clinical Trials Register DRKS00040598, registered on 12th June 2026. Retrospectively registered. RESULTS: Forty-eight patients were included (IG n = 21; CG n = 27; mean age 53.3 years; 68.8% females). At baseline, somatic symptom burden was high (SSS-8 M = 15.21; SD = 5.62) with clinically relevant depressive symptoms (PHQ-9 M = 10.94, SD = 4.61) and moderate anxiety (GAD-7 M = 7.22; SD = 4.38). Fatigue-related physical exhaustion and cognitive complaints were the most prominent symptoms. No significant efficacy of the psychotherapeutic group intervention over TAU was observed for SSS-8 (β = - 2.20, SE = 1.25, 95% CI [- 4.77, 0.38], t(27) = - 1.75, p = .091), PHQ-9 (β = - 1.77, SE = 1.51, 95% CI [- 4.87, 1.33], t(26) = - 1.18, p = .251), or GAD-7 (β = - 0.81, SE = 1.47, 95% CI [- 3.84, 2.22], t(26) = - 0.55, p = .588) comparing post-treatment outcomes in the IG with post-waiting outcomes in the CG. Baseline symptom severity robustly predicted post-randomization outcomes during the randomized phase (p < .001). CTS was no moderator for the intervention effect. CONCLUSIONS: In this exploratory randomized controlled trial, the intervention did not show significant superiority over the control condition; findings should be interpreted cautiously given limited statistical power. Future psychotherapeutic group interventions for patients with PCS have to consider outcome measures beyond severity of persistent physical symptoms rather than evaluating global symptom scores. Group-based psychotherapeutic approaches might benefit from flexibility in adaptation for individual patients' needs. Stratification by baseline severity and dominant symptom profiles (e.g., fatigue severity, trauma history) may improve sensitivity to clinically meaningful change. TRIAL REGISTRATION: Trial registration: DRKS German Clinical Trials Register DRKS00040598, registered on 12th June 2026. Retrospectively registered.