[Pubmed] Natural experiment on neuroinflammatory disease incidence and infection links pre- and post-COVID-19

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Brain. 2025 Dec 8:awaf458. doi: 10.1093/brain/awaf458. Online ahead of print.

ABSTRACT

Infections are recognised triggers for several neuroinflammatory disorders. The COVID-19 pandemic's nonpharmaceutical interventions sharply curtailed pathogen exposure, creating a natural experiment to test infection-disease links. Using Japan's National Claims Database, we first validated the nationwide decline with two strictly infection-dependent conditions-epidemic keratoconjunctivitis and influenza-associated encephalopathy-whose monthly incidences fell by >70% after April 2020. Next, we applied an interrupted time-series design, a causal-inference method for longitudinal data, to nine immune-mediated inflammatory diseases. Unsupervised clustering of model-derived level and slope changes identified three data-driven clusters. The first cluster, comprising Guillain-Barré syndrome and acute disseminated encephalomyelitis, showed large, statistically significant level drops (p < 0.001), particularly in women, consistent with infection-susceptible pathophysiology. The second cluster, including myasthenia gravis and optic neuritis, exhibited transient declines followed by significant positive post-intervention slopes (p < 0.001), suggesting deferred diagnosis, treatment interruption, or immune rebound. The third cluster, consisting of sarcoidosis, neuromyelitis optica, multiple sclerosis, Vogt-Koyanagi-Harada disease, and Behçet's disease, remained stable, suggesting limited or complex infectious links. These data-driven trajectories mirror clinical pathophysiology and demonstrate that reduced pathogen exposure affects neuroinflammatory disease onset to varying degrees. This framework supports infection-related risk stratification, preventive strategies, and continuity planning in neuroimmunology practice.

PMID:41359492 | DOI:10.1093/brain/awaf458


Source: https://pubmed.ncbi.nlm.nih.gov/4135949 ... 22+67771e2