This narrative review evaluated immune dysregulation across four post-infectious syndromes—PTLDS, long COVID, ME/CFS, and PANS/PANDAS—and assessed the rationale and evidence for immunomodulatory therapies including IVIG, rituximab, and therapeutic plasma exchange (TPE).
Evidence for immune-targeted treatments is strongest in patients with identifiable immunologic abnormalities. The phase III RituxME trial (rituximab in ME/CFS) and a phase II TPE trial in post-COVID both failed to show efficacy in unselected populations, highlighting the need for biomarker-guided patient selection.
Narrative review design limits causal inference; evidence synthesis across heterogeneous syndromes may obscure condition-specific signals; lack of controlled trials with immunologic phenotyping leaves treatment recommendations largely observational.
Avoid broad use of TPE or rituximab in unselected post-infectious syndrome patients—reserve immune-directed therapies for those with demonstrable autoantibody burden or defined immunologic phenotypes. Controlled trials with biomarker-based stratification are urgently needed.
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