Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation

Background: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features.

Methods: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria.

Results: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension.

Conclusions: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications.

Significance: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.