The article posits that a broader clinical and research framework — post-acute infection syndromes (PAISs) — is increasingly needed to understand a range of chronic illnesses that can follow acute infections. PAISs include conditions such as long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which share many common symptoms (fatigue, cognitive dysfunction, post-exertional malaise, unrefreshing sleep, orthostatic intolerance, etc.) despite being triggered by different infectious agents. These overlapping clinical features suggest shared underlying biological mechanisms and justify studying them collectively rather than as isolated diseases.
Komaroff highlights that while long COVID has brought widespread attention to post-infection sequelae, PAISs have long existed with diverse pathogens (viruses, bacteria, protozoa and fungi) acting as triggers. Both long COVID and ME/CFS can be debilitating and persist for months or years, affecting tens to hundreds of millions worldwide. The author emphasises that the biological abnormalities seen across PAISs — including immune dysregulation, neuroinflammation, endothelial dysfunction, mitochondrial and metabolic disturbances — point toward common pathological pathways.
Framing these illnesses under PAISs has several benefits: it encourages integrated research, helps clinicians recognise and validate post-infection conditions, and supports investigations into shared mechanisms that might lead to targeted diagnostics and treatments. However, PAIS remains under-recognised in medical practice and research funding, and more work is needed to define its causes, distinct subtypes, and effective clinical interventions.
Reference
A.L. Komaroff, Growing recognition of post-acute infection syndromes, Proc. Natl. Acad. Sci. U.S.A. 122 (29) e2513877122, https://doi.org/10.1073/pnas.2513877122 (2025).