Author Response: Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination
AnnaFrancis, NMO Clinical Fellow, John Radcliffe Hospital, Oxford
Submitted December 20, 2022
We thank the author for his interest but respectfully disagree with his statement that our conclusions are not supported by our data. We are cautious, stating ‘this suggests vaccination may influence the phenotypic presentation of MOGAD, and some adult-onset ADEM-like MOGAD cases might be triggered by environmental factors. Further study is required to determine the sequence of immunologic events that link vaccination and autoimmune CNS disease’.
In brief the author may have missed what mainly drove us to suggest this may be a rare association:
1) The cases occurred with the ChAdOx1S vaccine rather than the BNT162b2 vaccine, despite the latter vaccine being more commonly given to young adults in this period, and that this is the vaccine causing other immune conditions in a similar age group as our patients.
2) It was only the first and not subsequent vaccines doses that were associated with the onset attacks.
3) Optic neuritis is the commonest presentation in MOGAD and these patients were presenting with ADEM-like phenotypes.
4) It is not implausible that vaccination could occasionally trigger inflammatory CNS disease. Vaccination is an accepted trigger of ADEM1 and approximately 50% ADEM cases are associated with MOGAD antibodies2.
It is the above observations we were most interested in.
During the COVID pandemic, patterns of patient presentations were altered and generally reduced, so we agree that to rely on case patterns alone would not be enough. However, when we looked for seasonal variations in MOGAD attacks, we identified a single peak at the time vaccines were introduced but no seasonal variation in the preceding years of study. We agree this alone may invoke other hypotheses.
Our data is not at odds with the literature. The single NMOSD study by Qiu and colleagues cited in the letter looked only at a mixed cohort of aquaporin-4-positive and seronegative NMOSD, excluding those with MOGAD and those with monophasic disease, thereby losing many onset attacks. The other studies referenced (Jin et al., 2020; Spelman et al., 2014) report seasonal variations in attacks of multiple sclerosis and optic neuritis, which are clearly distinct from MOGAD.
We have in the Oxford National NMOSD service over 500 UK patients with aquaporin-4 antibody-positive-NMOSD and MOGAD and have one of the longest running NMOSD/MOGAD services. Analysis of this large dataset has not revealed seasonal variation in attacks, which is likely to be more relevant to UK patients than studies of different diseases or studies from Chinese cohorts.
Of note, several other studies from different parts of the world also report new-onset MOGAD following the Astra-Zeneca vaccine in case series (e.g., 3) and case reports (e.g., 4,5).
We do thank the author for his raising cautions and allowing us to highlight the main reasons for us reporting these cases. We hope these cases may afford an opportunity to better understand how MOGAD could be triggered by investigating these patients further.
Disclosures: Contact the editorial office at nnnjournal@neurology.org for the full disclosures.
2. Hennes EM, Baumann M, Schanda K, et al. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology. 2017;89(9):900-908
3. Netravathi M, Dhamija K, Gupta M, et al. COVID-19 vaccine associated demyelination & its association with MOG antibody. Mult Scler Relat Disord. 2022;60:103739. doi: 10.1016/j.msard.2022.103739.
4. Mumoli L, Vescio V, Pirritano D, Russo E, Bosco D. ADEM anti-MOG antibody-positive after SARS-CoV2 vaccination. Neurol Sci. 2022;43(2):763-766. doi: 10.1007/s10072-021-05761-7.
5. Sehgal V, Bansal P, Arora S, Kapila S, Bedi GS. Myelin Oligodendrocyte Glycoprotein Antibody Disease After COVID-19 Vaccination - Causal or Incidental? Cureus. 2022;14(7):e27024. doi: 10.7759/cureus.27024
We thank the author for his interest but respectfully disagree with his statement that our conclusions are not supported by our data. We are cautious, stating ‘this suggests vaccination may influence the phenotypic presentation of MOGAD, and some adult-onset ADEM-like MOGAD cases might be triggered by environmental factors. Further study is required to determine the sequence of immunologic events that link vaccination and autoimmune CNS disease’.
In brief the author may have missed what mainly drove us to suggest this may be a rare association:
1) The cases occurred with the ChAdOx1S vaccine rather than the BNT162b2 vaccine, despite the latter vaccine being more commonly given to young adults in this period, and that this is the vaccine causing other immune conditions in a similar age group as our patients.
2) It was only the first and not subsequent vaccines doses that were associated with the onset attacks.
3) Optic neuritis is the commonest presentation in MOGAD and these patients were presenting with ADEM-like phenotypes.
4) It is not implausible that vaccination could occasionally trigger inflammatory CNS disease. Vaccination is an accepted trigger of ADEM1 and approximately 50% ADEM cases are associated with MOGAD antibodies2.
It is the above observations we were most interested in.
During the COVID pandemic, patterns of patient presentations were altered and generally reduced, so we agree that to rely on case patterns alone would not be enough. However, when we looked for seasonal variations in MOGAD attacks, we identified a single peak at the time vaccines were introduced but no seasonal variation in the preceding years of study. We agree this alone may invoke other hypotheses.
Our data is not at odds with the literature. The single NMOSD study by Qiu and colleagues cited in the letter looked only at a mixed cohort of aquaporin-4-positive and seronegative NMOSD, excluding those with MOGAD and those with monophasic disease, thereby losing many onset attacks. The other studies referenced (Jin et al., 2020; Spelman et al., 2014) report seasonal variations in attacks of multiple sclerosis and optic neuritis, which are clearly distinct from MOGAD.
We have in the Oxford National NMOSD service over 500 UK patients with aquaporin-4 antibody-positive-NMOSD and MOGAD and have one of the longest running NMOSD/MOGAD services. Analysis of this large dataset has not revealed seasonal variation in attacks, which is likely to be more relevant to UK patients than studies of different diseases or studies from Chinese cohorts.
Of note, several other studies from different parts of the world also report new-onset MOGAD following the Astra-Zeneca vaccine in case series (e.g., 3) and case reports (e.g., 4,5).
We do thank the author for his raising cautions and allowing us to highlight the main reasons for us reporting these cases. We hope these cases may afford an opportunity to better understand how MOGAD could be triggered by investigating these patients further.
Disclosures: Contact the editorial office at nnnjournal@neurology.org for the full disclosures.
References
1. Torisu H, Okada K. Vaccination-associated acute disseminated encephalomyelitis. Vaccine. 2019;37(8):1126-1129.
2. Hennes EM, Baumann M, Schanda K, et al. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology. 2017;89(9):900-908
3. Netravathi M, Dhamija K, Gupta M, et al. COVID-19 vaccine associated demyelination & its association with MOG antibody. Mult Scler Relat Disord. 2022;60:103739. doi: 10.1016/j.msard.2022.103739.
4. Mumoli L, Vescio V, Pirritano D, Russo E, Bosco D. ADEM anti-MOG antibody-positive after SARS-CoV2 vaccination. Neurol Sci. 2022;43(2):763-766. doi: 10.1007/s10072-021-05761-7.
5. Sehgal V, Bansal P, Arora S, Kapila S, Bedi GS. Myelin Oligodendrocyte Glycoprotein Antibody Disease After COVID-19 Vaccination - Causal or Incidental? Cureus. 2022;14(7):e27024. doi: 10.7759/cureus.27024