Comparison of the symptom networks of long-COVID and chronic fatigue syndrome: From modularity to connectionism

The objective was to compare the symptom networks of long-COVID and chronic fatigue syndrome (CFS) in conjunction with other theoretically relevant diagnoses in order to provide insight into the etiology of medically unexplained symptoms (MUS). This was a cross-sectional comparison of questionnaire items between six groups identified by clinical diagnosis. All participants completed a 65-item psychological and somatic symptom questionnaire (GSQ065). Diagnostically labelled groups were long-COVID (N = 107), CFS (N = 254), irritable bowel syndrome (IBS, N = 369), fibromyalgia (N = 1,127), severe asthma (N = 100) and healthy group (N = 207). The 22 symptoms that best discriminated between the six groups were selected for network analysis. Connectivity, fragmentation and number of symptom clusters (statistically related symptoms) were assessed. Compared to long-COVID, the symptom networks of CFS, IBS and fibromyalgia had significantly lower connectivity, greater fragmentation and more symptom clusters. The number of clusters varied between 9 for CFS and 3 for severe asthma, and the content of clusters varied across all groups. Of the 33 symptom clusters identified over the six groups 30 clusters were unique. Although the symptom networks of long-COVID and CFS differ, the variation of cluster content across the six groups is inconsistent with a modular causal structure but consistent with a connectionist (network, parallel distributed processing) biological basis of MUS. A connectionist structure would explain why symptoms overlap and merge between different functional somatic syndromes, the failure to discover a biological diagnostic test and how psychological and behavioral interventions are therapeutic.