Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

Observed Findings

• A single latent trait explained 64.8% of shared variance across 30 symptoms, with positive loadings for all measured symptoms.
• Fatigue, psychiatric symptoms, and cognitive impairment were the most discriminative symptoms (IRT coefficients >1.5, p<0.001).
• Increased latent trait severity was associated with decreased body weight and reduced physical performance (β>0.240, p≤0.003).
• Greater symptom severity correlated with elevated C-reactive protein (β=0.378, 95% CI 0.215–0.541, p<0.001) and D-dimer (β=0.412, 95% CI 0.123–0.702, p=0.005).
• Results remained significant after excluding subjects with pro-inflammatory comorbidities, suggesting findings were not driven by pre-existing inflammatory conditions.

Inferred Conclusions

• Multiple persistent post-COVID symptoms reflect a single underlying disease process or latent trait, rather than independent problems.
• Fatigue and neuropsychiatric manifestations are core features of PASC and may serve as sensitive markers of disease severity.
• Objective signs of systemic inflammation (elevated CRP and D-dimer) and physical disability represent measurable biological correlates of PASC symptom burden.
• The unified latent trait model suggests PASC is a coherent medical condition with biological underpinnings, not a collection of psychogenic complaints.

Remaining Questions