Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore

ABSTRACT Background Emerging evidence suggests a potential association between COVID‐19 and autoimmune encephalitis (AE). We aimed to evaluate the positivity rate of AE‐ and paraneoplastic neurological syndromes (PNS)‐associated antibodies in relation to COVID‐19. Methods We investigated the frequen...

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Main Authors: Rui Ling Rena Lau, Karine Su Shan Tay, Seyed Ehsan Saffari, Patricia Yut Wan Wong, Mei Ting Lim, Angelia Swee Hoon Koe, Jeanne May May Tan, Kok Pin Yong, Kevin Tan, Josiah Yui Huei Chai, Tianrong Yeo
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Brain and Behavior
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Online Access:https://doi.org/10.1002/brb3.70630
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author Rui Ling Rena Lau
Karine Su Shan Tay
Seyed Ehsan Saffari
Patricia Yut Wan Wong
Mei Ting Lim
Angelia Swee Hoon Koe
Jeanne May May Tan
Kok Pin Yong
Kevin Tan
Josiah Yui Huei Chai
Tianrong Yeo
author_facet Rui Ling Rena Lau
Karine Su Shan Tay
Seyed Ehsan Saffari
Patricia Yut Wan Wong
Mei Ting Lim
Angelia Swee Hoon Koe
Jeanne May May Tan
Kok Pin Yong
Kevin Tan
Josiah Yui Huei Chai
Tianrong Yeo
author_sort Rui Ling Rena Lau
collection DOAJ
description ABSTRACT Background Emerging evidence suggests a potential association between COVID‐19 and autoimmune encephalitis (AE). We aimed to evaluate the positivity rate of AE‐ and paraneoplastic neurological syndromes (PNS)‐associated antibodies in relation to COVID‐19. Methods 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. Results A total of 87 of 4347 samples and 29 of 3393 samples tested for AE‐ and PNS‐associated antibodies, respectively, were positive. A spike in the incidence of AE‐associated antibodies was observed in 2020 at 4.92 (95% CI, 3.05–7.53) per 1,000,000 person‐years, coinciding with the first year of the COVID‐19 “pandemic outbreak.” The cumulative incidence in the “pre‐pandemic” period from 2017 to 2019 was 2.44 (95% CI, 1.66–3.46) per 1,000,000 person‐years (p = 0.034, vs. “pandemic outbreak”), and in the “mid to late pandemic” period from 2021 to 2023, this was 2.74 (95% CI, 1.91–3.82) per 1,000,000 person‐years (p = 0.086, vs. “pandemic outbreak”). The incidence of PNS‐associated antibodies was unaffected by the COVID‐19 pandemic. Conclusions The increased incidence of AE‐associated antibodies during the COVID‐19 “pandemic outbreak” suggests a potential biological link. The subsequent decline in incidence in the “mid to late pandemic” period may be attributable to widespread vaccination and the emergence of new viral variants with less potential to induce autoimmunity. The incidence of PNS‐associated antibodies was stable throughout, reinforcing its primary association with malignancy.
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spelling doaj-art-94c198dba6c84576b3174a64e435902c2025-08-20T03:09:00ZengWileyBrain and Behavior2162-32792025-07-01157n/an/a10.1002/brb3.70630Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in SingaporeRui Ling Rena Lau0Karine Su Shan Tay1Seyed Ehsan Saffari2Patricia Yut Wan Wong3Mei Ting Lim4Angelia Swee Hoon Koe5Jeanne May May Tan6Kok Pin Yong7Kevin Tan8Josiah Yui Huei Chai9Tianrong Yeo10Duke‐NUS Medical School National University of Singapore Singapore SingaporeNeuromuscular Laboratory National Neuroscience Institute Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeNeuromuscular Laboratory National Neuroscience Institute Singapore SingaporeNeuromuscular Laboratory National Neuroscience Institute Singapore SingaporeNeuromuscular Laboratory National Neuroscience Institute Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeDuke‐NUS Medical School National University of Singapore Singapore SingaporeABSTRACT Background Emerging evidence suggests a potential association between COVID‐19 and autoimmune encephalitis (AE). We aimed to evaluate the positivity rate of AE‐ and paraneoplastic neurological syndromes (PNS)‐associated antibodies in relation to COVID‐19. Methods 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. Results A total of 87 of 4347 samples and 29 of 3393 samples tested for AE‐ and PNS‐associated antibodies, respectively, were positive. A spike in the incidence of AE‐associated antibodies was observed in 2020 at 4.92 (95% CI, 3.05–7.53) per 1,000,000 person‐years, coinciding with the first year of the COVID‐19 “pandemic outbreak.” The cumulative incidence in the “pre‐pandemic” period from 2017 to 2019 was 2.44 (95% CI, 1.66–3.46) per 1,000,000 person‐years (p = 0.034, vs. “pandemic outbreak”), and in the “mid to late pandemic” period from 2021 to 2023, this was 2.74 (95% CI, 1.91–3.82) per 1,000,000 person‐years (p = 0.086, vs. “pandemic outbreak”). The incidence of PNS‐associated antibodies was unaffected by the COVID‐19 pandemic. Conclusions The increased incidence of AE‐associated antibodies during the COVID‐19 “pandemic outbreak” suggests a potential biological link. The subsequent decline in incidence in the “mid to late pandemic” period may be attributable to widespread vaccination and the emergence of new viral variants with less potential to induce autoimmunity. The incidence of PNS‐associated antibodies was stable throughout, reinforcing its primary association with malignancy.https://doi.org/10.1002/brb3.70630antibodiesautoimmune encephalitisCOVID‐19incidenceparaneoplastic neurological syndrome
spellingShingle Rui Ling Rena Lau
Karine Su Shan Tay
Seyed Ehsan Saffari
Patricia Yut Wan Wong
Mei Ting Lim
Angelia Swee Hoon Koe
Jeanne May May Tan
Kok Pin Yong
Kevin Tan
Josiah Yui Huei Chai
Tianrong Yeo
Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
Brain and Behavior
antibodies
autoimmune encephalitis
COVID‐19
incidence
paraneoplastic neurological syndrome
title Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
title_full Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
title_fullStr Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
title_full_unstemmed Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
title_short Impact of the COVID‐19 Outbreak on the Incidence of Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Associated Antibodies in Singapore
title_sort impact of the covid 19 outbreak on the incidence of autoimmune encephalitis and paraneoplastic neurological syndromes associated antibodies in singapore
topic antibodies
autoimmune encephalitis
COVID‐19
incidence
paraneoplastic neurological syndrome
url https://doi.org/10.1002/brb3.70630
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