Core features and inherent diversity of post-acute infection syndromes.

Observed Findings

• PAIS share a common core of four symptoms: pathological fatigue, cognitive problems, sleep disorders, and pain
• Symptoms typically begin suddenly after an apparently common infection and persist for years with periods of relapse and remission
• Clinical presentation varies substantially depending on the initial pathogen and individual pre-existing factors
• Multiple biological mechanisms are implicated including immune dysregulation, mitochondrial dysfunction, and tryptophan-kynurenine pathway disruption
• Interoceptive dysfunction may be central to understanding fatigue, dysautonomia, and HPA axis dysfunction in PAIS

Inferred Conclusions

• PAIS represent self-sustained pathological processes involving both core and diverse symptoms that develop from individual predispositions interacting with infection-triggered biological changes
• Characterization of PAIS heterogeneity requires composite assessment including biomarkers, questionnaires, and functional tests rather than single diagnostic parameters
• Interoceptive dysfunction provides a unifying nervous system mechanism linking diverse PAIS manifestations
• Multiple self-sustained biological loops (immune, metabolic, mitochondrial) can assemble in different combinations across individuals, explaining symptom variability

Remaining Questions