Low-grade persistent poliovirus infection in long-term polio survivors diagnosed with post-polio syndrome: diagnostic and clinical implications.

Despite extensive research, the pathogenesis of Post-Polio Syndrome (PPS) remains unclear. We investigated 251 participants from Northern Italy: long-term polio survivors with PPS, long-term polio survivors with stable polio, family members of both groups, subjects with neurological disorders other than poliomyelitis, and healthy controls. This study investigated whether persistent viral activity or the existence of viral reservoirs contributes to causing PPS. Poliovirus (PV) genomes and proteins were detected in 87.2% of PPS cases versus 12.0% of stable polio cases and 3.5% of control family members, but not in pathologic and healthy controls. Among PPS patients, the highly concordant detection of PV strains in both peripheral blood leukocytes and cerebrospinal fluid (CSF) suggests the presence of an ongoing low-grade infection. Conversely, the very low detection rate in family members indicates the minimal transmissibility of these PV variants. Molecular analysis of the detected PV strains revealed mutations across most genome regions, likely leading to defects in virus replication. Furthermore, in cell cultures, PPS-derived PV strains induced the release of inflammatory mediators (IL6, IL8, MCP1) that may play a pathogenic role. These findings have several clinical implications. First, the presence of mutated PV forms in blood leukocytes and CSF could serve as a diagnostic marker for PPS. Second, the persistent virus infection suggests that antiviral treatments might help reduce PPS progression. Furthermore, advanced genome sequencing techniques hold potential for distinguishing vaccine-derived from wild-type PV strains, thereby refining our understanding of PPS and the full spectrum of polio disorders.