Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study

Abstract

Background: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort.

Methods: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found.

Results: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients.

Conclusions: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.

Keywords: Clusters; Fatigue; Long COVID; ME/CFS; Persistent symptoms; Post COVID-19 condition; Post-viral condition.

Fig. 1

Symptom-based clusters at visit 1 using self-organizing maps. All clusters of patients are displayed in the direction of left to right and bottom to top. Each hexagon represents a cluster, and the number within a hexagon shows the number of patients in the cluster. The x-axis and y-axis indicate the number of clusters, starting from 0. In particular, coordinate (0,0) corresponds to Cluster 1, coordinate (1,0) corresponds to Cluster 2, etc.

Fig. 2

Symptom-based clusters at visit 2 using self-organizing maps. All clusters of patients are displayed in the direction of left to right and bottom to top. Each hexagon represents a cluster, and the number within a hexagon shows the number of patients in the cluster. The x-axis and y-axis indicate the number of clusters, starting from 0. In particular, coordinate (0,0) corresponds to Cluster 1, coordinate (1,0) corresponds to Cluster 2, etc.