A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study

Objective To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. Design Prospective, multicentre cohort study. Setting Six Dutch hospitals. Participants 205 initially hospitalized (March-June 2020), confirmed SARS-CoV-2 patients, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, MRI contraindication, or severe neurological damage post-hospital discharge. Interventions Not applicable. Main Outcome Measures Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences following Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: 1. Demographic and premorbid factors (sex, age, education, comorbidities), 2. Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), 3. Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), and 4. Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), 5. Fatigue or cognitive complaints. Results The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (p=.01), lower PROMIS-PF (p<.001), higher HADS-Depression (p=.03), and CLC-high (p=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, p<.05). Conclusions Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.