This study evaluated central sensitization (CS) in 169 consecutive patients with Long COVID who were referred for assessment of orthostatic intolerance. CS, measured using the Central Sensitization Inventory, was present in 81% of participants. The CS group included a higher proportion of females (79.6%) compared with the non-CS group (53.1%), and this difference reached statistical significance (p = 0.004).
Demographic and diagnostic group differences reported in the abstract indicate that CS in this cohort clustered with certain clinical features and comorbid diagnoses, which are detailed in subsequent sections.
Patients classified with CS had higher rates of several comorbid conditions, including anxiety, depression, fibromyalgia, and headaches, relative to patients without CS. Across standardized symptom measures, those with CS reported a greater burden:
All comparisons of symptom burden between CS and non-CS groups were reported as statistically significant (all p < 0.001) in the abstract, indicating robust differences in self-reported autonomic, sensory, and general health symptoms associated with CS in this Long COVID sample.
Objective autonomic function testing performed in the cohort included deep breathing, the Valsalva maneuver, and a head-up tilt test with concurrent transcranial Doppler and capnography monitoring. These tests were used to characterize autonomic physiology and orthostatic responses.
Despite higher self-reported autonomic symptom burden among patients with CS, the frequency of autonomic failure—most commonly mild—was similar between groups: 84.7% in the CS group versus 84.4% in the non-CS group (p = 0.999). This finding suggests a disconnect between objective autonomic failure prevalence and subjective autonomic symptom severity in this referral population.
During orthostatic testing, changes in cerebral blood flow velocity were measured using transcranial Doppler. The CS group demonstrated a greater decline in orthostatic cerebral blood flow velocity compared with the non-CS group. Reported values were a mean decline of -25.53% ± 11.19 in the CS group versus -22.09% ± 10.53 in those without CS, with this difference achieving statistical significance (p = 0.038).
The authors interpret this greater orthostatic reduction in cerebral blood flow velocity as evidence of more pronounced cerebral hypoperfusion during orthostasis among patients with CS, which could contribute to symptom generation in Long COVID.
Interleukin-6 (IL-6) levels were higher in patients with CS compared with those without CS (p = 0.041), as reported in the abstract. The elevated IL-6 is presented as consistent with a potential neuroinflammatory component related to CS in Long COVID.
No additional cytokines, longitudinal inflammatory profiles, or thresholds for clinical interpretation of IL-6 were provided in the abstract. Details beyond the reported association were not available in the source text provided.
Skin biopsies were performed to assess small-fiber pathology. The prevalence of abnormal skin biopsy findings was comparable between the CS and non-CS groups: 50.8% versus 52.0%, respectively (p = 0.999). This result indicates no clear difference in small-fiber structural abnormalities between groups based on the abstract data.
The authors report that small-fiber abnormality prevalence did not distinguish the CS subgroup from the remainder of the cohort in this sample.
From the data summarized in the abstract, the investigators conclude that central sensitization is highly prevalent among patients with Long COVID referred for orthostatic intolerance and may contribute to their multisystem symptomatology. Two pathophysiological mechanisms highlighted in the abstract as potentially underpinning CS in this population are:
The abstract further notes that autonomic failure and small-fiber pathology were not different in frequency between CS and non-CS groups, suggesting that CS-related symptoms may arise through mechanisms other than measurable autonomic failure or small-fiber loss in this cohort.
The provided source text is the PubMed abstract. It reports cohort size, key outcome comparisons, and p values for main findings. However, several details commonly sought for critical appraisal are not included in the abstract text and therefore were not available here, including:
These specific methodological and contextual details were not reported in the abstract provided and would require consultation of the full text for comprehensive appraisal.
Overall, the abstract indicates a high prevalence of central sensitization in this referral cohort of Long COVID patients and identifies associated features—greater subjective symptom burden, larger orthostatic cerebral blood flow reductions, and higher IL-6—that the authors suggest may reflect cerebral hypoperfusion and neuroinflammation as contributors to CS-related symptomatology in Long COVID.