Fatigue can influence the development of late-onset pain in post-COVID-19 syndrome: An observational study

Background: Late-onset pain is frequent following COVID-19, and many pathogenetic mechanisms have been proposed. Identifying the main features of patients may help in designing tailored rehabilitative interventions.Methods: We enrolled post-COVID-19 patients with an increase in pain intensity of two points on the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) at 52 weeks compared to the pre-COVID-19 condition. All subjects were retrospectively monitored at 12, 26, and 52 weeks. A specific pain assessment was performed to determine the characteristics and mechanisms of pain. Catastrophizing, kinesiophobia, and other psychological symptoms were evaluated. The pressure pain threshold (PPT) and temporal summation (TS) were measured and compared in age- and sex-matched healthy controls to analyse pain characteristics.Results: A total of 67 patients were recruited, with 20 of them presenting an increase in pain at 52 weeks. Subjects of the two subgroups were similar in demographic and clinical characteristics at baseline; significant differences in fatigue, anxiety, mobility, ability to perform daily activities, and general health perception were recorded at 26 weeks. Fatigue significantly predicted pain onset (beta = 0.54, p = 0.002). Sixteen different body regions were identified as painful, with a pain intensity of 6.0 +/- 1.9. Most of the samples did not show neuropathic or nociplastic mechanisms. No differences in PPT and TS were recorded between patients and healthy controls.Conclusions: Almost one out of three patients hospitalized for COVID-19 developed pain 1 year later, and fatigue seems responsible for chronicity. An overlapping of conditions may explain late-onset post-COVID-19 pain, and a comprehensive approach must be considered for patient management.Significance: Late-onset pain is frequent in post-COVID-19 syndrome and an overlapping of different mechanisms seems to be responsible for its development. Among many predisposing factors, fatigue in the months before seems to be one of the primary causes of pain one year following infection and its management may help to identify new strategies for prevention and treatment of late-onset pain.