Chronic fatigue syndrome in long COVID: prevalence and impact on health-related quality of life and health status. A cross-sectional study. BioICOPER study

Long COVID (LC) and Chronic Fatigue Syndrome (CFS) share clinical features and are associated with reduced quality of life and functional impairment. However, evidence regarding the additional health burden associated with LC–CFS overlap remains limited. We aimed to assess the prevalence of LC–CFS overlap and its association with health-related quality of life (HRQoL) and health status outcomes, including sex differences. Cross-sectional study including 304 patients with LC. CFS was diagnosed using Fukuda criteria. Health status and HRQoL were assessed with Short Form-36 Survey (SF-36), Goldberg’s Anxiety and Depression Scale (GADS), Post-COVID19 Functional Scale (PCFS), Spanish Chronic Pain Grade Scale (SCPGS), modified Medical Research Council Dyspnea Scale (mMRC) and Malnutrition Universal Screening Tool (MUST). Group comparisons and adjusted regression models were performed. In addition, a sex-by-LC-CFS overlap interaction term was included in all regression models. 171 subjects (56.3%) met LC-CFS overlap, more frequently in women (63.8% vs. 40.2%). CFS overlap group was related with worse outcomes compared with those with LC alone in most of health questionnaires, including SF-36, GADS, SCPGS, PCFS and mMRC. Compared with LC alone, LC-CFS overlap was associated with poorer scores in SF-36 physical and mental health components (PCS: B=-9.73, MCS: B=-5.36), anxiety (B = 2.02), depression (B = 2.83), SCPGS (B = 12.56), PCFS A component (OR = 13.98) and B component (OR=11.27), and mMRC (OR = 7.17). No association was observed with MUST and no evidence of effect modification by sex was found. Over half of patients met criteria for LC–CFS overlap, more frequently in women. This subgroup showed worse HRQoL and health status. Identifying overlap in Primary Care may identify patients with greater clinical and support targeted management strategies. This study was carried out with data from subjects of BioICOPER project. The study protocol has been published, and it has been registered in ClinicalTrials.gov in April 2023 with the registration number NCT05819840.