Herbal medicine (Kyungok-go) for fatigue in Long COVID patients: A prospective multicenter pilot study

Background: Long COVID, defined as symptoms persisting beyond 12 weeks after acute SARS-CoV-2 infection, has emerged as a significant global health concern. Fatigue is one of its most common and disabling symptoms, yet robust clinical evidence for effective treatments remains limited. Methods: We conducted a multicenter, prospective, single-arm pilot study to evaluate the feasibility and potential effectiveness of Kyungok-go (Qiong-Yu-Gao), a traditional Korean herbal medicine, in individuals with Long COVID-related fatigue. A total of 100 participants experiencing fatigue for at least 12 weeks following a COVID-19 diagnosis received Kyungok-go (22.5 g twice daily) for 12 weeks. The primary outcome was the change in Fatigue Severity Scale (FSS) scores. Secondary outcomes included fatigue severity assessed by a Visual Analog Scale (VAS) and the Chalder Fatigue Scale (ChFS), along with sleep quality, depressive symptoms, cognitive and physical function, and quality of life. Feasibility was assessed through recruitment rate, treatment adherence, and dropout rates. Results: Ninety-four participants completed the study. FSS scores improved significantly (mean difference (MD) -2.1; 95% CI, -2.4, -1.9), accompanied by significant reductions in fatigue severity on the VAS (MD -35.6; 95% CI, -39.7, -31.4) and ChFS total score (MD -29.1; 95% CI, -32.3, -25.9). Sleep quality (MD -4.0; 95% CI, -4.8, -3.2), depressive symptoms (MD -8.1; 95% CI, -9.6, -6.7), and overall quality of life (EQ-5D-5L, MD 0.1; 95% CI, −0.1, 0.1) also showed improvements. Cognitive (MD 0.9; 95% CI, 0.2, 1.5) and physical function (MD 0.2; 95% CI, 0.0, 0.3) showed modest or limited changes. Medication adherence exceeded 97%, and no serious treatment-related adverse reactions were observed. Conclusion: Kyungok-go was well-tolerated and showed promising effects in alleviating fatigue among patients with Long COVID. These findings support its feasibility and potential as a therapeutic option, warranting further evaluation in randomized controlled trials. Trial registration: CRIS, KCT0009410 (https://cris.nih.go.kr/).