We aimed to evaluate the occurrence of antibody-positive AE and paraneoplastic neurological syndromes (PNS) in relation to COVID-19.

While COVID-19 infection is primarily recognised for causing respiratory symptoms, emerging evidence suggests it may precipitate autoimmune neurological conditions, including autoimmune encephalitis (AE). The aetiology for this is unclear; proposed mechanisms include molecular mimicry and immune system dysregulation.

We investigated the frequency and incidence of AE- and PNS-associated antibodies amongst clinical tests performed at the National Neuroscience Institute, Singapore, before and during the COVID-19 pandemic. Antibodies against surface-exposed antigens associated with AE were tested using cell-based assays; antibodies against intracellular antigens in PNS were detected by immunoblot and tissue-based assays. 

From 2017-2023, 4,347 samples were screened for AE Ab; 87 were positive (43 NMDAR, 29 LGI1, 13 GABA_b, 1 CASPR2, 1 DPPX). From 2018-2023, 29 of 3,393 samples tested for PNS Ab were positive (9 GAD, 5 Yo, 4 Hu, 3 SOX1, 2 Zic4, 2 Ri, 1 Ma2, 1 Tr, 1 CV2, 1 Amphiphysin). A spike in incidence of AE-associated antibodies was observed in 2020 at 4.92 (95% CI 3.05-7.53)/100,000, coinciding with the COVID-19 ‘outbreak’. The cumulative incidence in the ‘pre-pandemic’ period from 2017 to 2019 was 2.44 (95% CI 1.66–3.46)/100,000 (p=0.034, vs. ‘outbreak’), and in the ‘post-outbreak’ period from 2021 to 2023, this was 2.74 (95% CI 1.91–3.82)/100,000 (p=0.086, vs. ‘outbreak’). Incidence of PNS-associated antibodies was unaffected by COVID-19.

The temporal association of Ab positive AE and COVID-19 outbreak suggests a potential causal link. Subsequent decline in cases may be due to SARS-CoV2 vaccination and new variants. PNS incidence remained stable, given its association with malignancy.