Clinical Review & Education

JAMA Neurology | Review

SARS-CoV-2 Vaccination and Neuroimmunological Disease

A Review
Alice Grizzel Willison, MRes, MBChB; Marc Pawlitzki, MD; Michael Peter Lunn, MA, MBBS, PhD;
Hugh John Willison, MBBS, PhD; Hans-Peter Hartung, MD; Sven Günther Meuth, MD, PhD

Supplemental content
IMPORTANCE The temporal association between the occurrence of neurological diseases, CME at jamacmelookup.com
many autoimmune diseases, and vaccination against SARS-CoV-2 has been topically
interesting and remains hotly debated both in the medical literature and the clinic. Given the
very low incidences of these events both naturally occurring and in relation to vaccination,
it is challenging to determine with certainty whether there is any causative association and
most certainly what the pathophysiology of that causation could be.

OBSERVATIONS Data from international cohorts including millions of vaccinated individuals

suggest that there is a probable association between the adenovirus-vectored vaccines and
Guillain-Barré syndrome (GBS). Further associations between other SARS-CoV-2 vaccines and
GBS or Bell palsy have not been clearly demonstrated in large cohort studies, but the possible
rare occurrence of Bell palsy following messenger RNA vaccination is a topic of interest.
It is also yet to be clearly demonstrated that any other neurological diseases, such as central
nervous system demyelinating disease or myasthenia gravis, have any causative association
with vaccination against SARS-CoV-2 using any vaccine type, although it is possible that
vaccination may rarely trigger a relapse or worsen symptoms or first presentation
Author Affiliations: Author
in already-diagnosed or susceptible individuals. affiliations are listed at the end of this
article.
CONCLUSIONS AND RELEVANCE The associated risk between SARS-CoV-2 vaccination and
Corresponding Author: Hans-Peter
GBS, and possibly Bell palsy, is slight, and this should not change the recommendation for Hartung, MD (hans-peter.hartung@
individuals to be vaccinated. The same advice should be given to those with preexisting uni-duesseldorf.de), and Sven
neurological autoimmune disease. Günther Meuth, MD, PhD (meuth@
uni-duesseldorf.de), Department of
Neurology, University Hospital
JAMA Neurol. 2024;81(2):179-186. doi:10.1001/jamaneurol.2023.5208 Düsseldorf, Medical Faculty, Heinrich
Published online January 16, 2024. Heine University, Universitätsstraße 1,
40225 Düsseldorf, Germany.

I
nfection with SARS-CoV-2 results in COVID-19 in many, which specific complication of the adenoviral vector (AV) ChAdOx1 (Oxford/
can be severe in some. After a year of variable worldwide AstraZeneca) and Ad26.COV2.S (Janssen) vaccines. 3,4 An
government-mandated social restrictions, the arrival in 2021 increased risk of developing other neurological autoimmune disor-
of vaccines against SARS-CoV-2 was very welcome. These used new ders has been extensively sought, but only the very low incidence
medical technologies, and there was public and medical concern of Guillain-Barré syndrome (GBS) following AV vaccine administra-
about any potential serious neurological adverse effects that might tion has been supported by significant evidence.
occur. As a result, passive and active academic and international clini-
cal surveillance systems focused on public reassurance and ensur-
ing pharmacological safety. The neurological diseases of concern, in-
Methods
cluding specific adverse events of special interest, are all individually
rare. Most occur with a background incidence of naturally occur- Study Selection
ring disease recorded with variable accuracy in nonpandemic his- We performed an extensive literature search for this narrative re-
torical cohorts. Furthermore, a heterogeneity of ascertainment, re- view in the PubMed and Scopus databases, with no limitation on the
cording, and coding strategies have hampered efforts to identify or time period searched, using the MeSH search terms “COVID-19” OR
refute causality. The reporting systems in place are by necessity usu- “SARS-CoV-2” AND “vaccination” AND “autoimmune,” returning 1005
ally passive, with variable ability to corroborate reports and clean articles in PubMed and 1364 articles in Scopus (Figure 1; eMethods
data. Rarely, reliable active ascertainment methods can generate 1 in the Supplement). Relevant studies for inclusion were identified
more accurate data.1 In general, evidence that vaccination is caus- by A. G. W. and M. P., who independently screened all titles and ab-
ally significant in the pathogenesis of autoimmune neurological syn- stracts. A hierarchical selection was used where only high-quality
dromes is rarely validated even by large, well-conducted epidemio- epidemiological studies exploring millions of participants or vac-
logical studies.2 An almost unique exception to this is the cerebral cine doses were included to review the highest certainty evidence.
venous sinus thrombosis, now termed vaccine-associated immune Case studies have only been included where no or very few large
thrombosis and thrombocytopenia (VITT), identified as a rare and studies were identified.

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 Clinical Review & Education Review SARS-CoV-2 Vaccination and Neuroimmunological Disease

Figure 1. PRISMA Flow Diagram

2369 Articles identified through 44 Articles identified through

literature search other sources The first phase of screening excluded
1364 Scopus database 1343 articles. Articles that did not
1005 PubMed database include millions of vaccine doses of
millions of vaccinated patients were
removed if there existed articles
including this number of patients or
1415 Articles after duplicates vaccinations, for example, for
removed Guillain-Barré syndrome. If, as was
1343 Excluded the case of myasthenia gravis, there
was insufficient evidence including
72 Articles identified after title
millions of patients or vaccine doses,
and abstract screening
the articles evaluating the largest
21 Additional articles identified through reference list cohort of patients were included in
searching of 72 articles and the PubMed Cited by feature
the analysis. Articles were screened
93 Full-text articles assessed for a focus on neurological disease
for eligibility occurrence or worsening following
24 Excluded SARS-CoV-2 vaccination. Neurological
17 Case reports or series that were not required due
disease included central and
to the availability of larger studies
7 Articles that described neurological illness following peripheral nervous system
SARS-CoV-2 infection, not following vaccination complications, including but not
69 Studies included in analyses limited to autoimmune diseases,
cerebrovascular disease, and
psychiatric disease.

Statistical Analysis Intravenous Immunoglobulin (IVIG) used by Keh et al.1 The risk of
The forest plot (Figure 1) was created using data hand-extracted from overrepresenting the incidence of neurological disease following vac-
10 articles that recorded cases of GBS following an AV vaccine, the cination is further increased by the background rates of relatively
background incidence in their cohort—or, where the background in- mild diseases being underestimated in some epidemiological co-
cidence could be taken from another cohort, which was possible for horts. People with mild GBS or mild Bell palsy may not present to
the British data—and the number of vaccinated individuals for that hospital, and so the true background rate may well be higher than
specific vaccine. Articles containing GBS data not included in the plot the background rate estimated by the literature. This imbalance is
did not include the parameters needed to calculate the excess cases problematic for then understanding true incidences following vac-
per 100 000 vaccines—for example, only the total number of GBS cination. Additionally, the diagnostic certainty of GBS, Bell palsy,
cases for a given vaccine with no expected or background rate avail- myasthenia gravis, and other diseases is often very limited in pas-
able or without the total number of individuals vaccinated using a sive systems, and to our knowledge, only the NHSE IVIG database
specific vaccine. The excess cases per 100 000 vaccines and the 95% had some prospective diagnostic check. In the Yellow Card UK data
CI were calculated from the number of vaccinated individuals for a set, fewer than 20% of patients were in a diagnostic certainty
given vaccine as well as the number of excess GBS cases in that category or had a Brighton score of 1 to 3.
population. The parameters were calculated in Excel version 16.69
(Microsoft), and the plot was created in RStudio version 2022.12.0
(Posit) using the ggplot2 package.
Observations: Neuroimmunological Complications
of SARS-CoV-2 Vaccination
GBS
Limitations of the Current Evidence
The most frequently investigated temporal association between an
These data are all particularly vulnerable to small study effects, pub- autoimmune neurological disease and SARS-CoV-2 vaccination
lication bias, outcome reporting bias, and clinical heterogeneity, as was GBS, an acute-onset immune-mediated postinfectious
neurological disease following SARS-CoV-2 vaccination is rare, event polyradiculoneuropathy.5 The background incidence of GBS in North
numbers are small, and public interest due to the COVID-19 pan- America and Europe is approximately between 0.8 and 1.9 (me-
demic is huge. We therefore preferentially selected large cohort stud- dian, 1.11) cases per 100 000 person-years.6 GBS usually occurs
ies for this review. Even in these studies, acquisition bias is impor- within 4 weeks of a triggering infection, but an interval of up to 6
tant, as the interest in GBS, facial palsy, and other neurological weeks was established following swine flu vaccination in 1976/
diseases likely led to significant overreporting or duplicate report- 1977, and the consensus is to consider this period of vaccination-
ing. As illustrated in data from the UK, cohorts often interrogated attributable risk the same as the infection’s at-risk period.1,7 Numer-
the same data sets, and so cohorts reporting the same participant ous studies based on national or insurance-based surveillance
were reported in more than 1 article. Multiple reporting of patients systems have been published, many including millions of vaccines
also occurred in the passively reported Yellow Card system in the UK or vaccinated individuals (Table 1).1,8-17 We present these sepa-
and possibly Vaccine Adverse Events Reporting System (VAERS) in rated by country. The major differences in certainty of the conclu-
the US; these systems have limited cross-checking and data clean- sions are diagnostic categorization (from patient-reported passive
ing methods, unlike the National Health Service England (NHSE) reporting to dedicated clinician-identified and criterion-supported

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 SARS-CoV-2 Vaccination and Neuroimmunological Disease Review Clinical Review & Education

Table 1. Association Between Vaccination and Guillain-Barré Syndrome (GBS)

Postvaccination
Vaccinated individuals/ risk window Period of Possible
Source Study type administered doses, No. of interest Country data collection associations
Walker et al,8 Self-controlled Vaccinated individuals: 4-42 d for GBS; UK July 2020- ChAdOx1 and GBS
2022 case series 7 783 441 with ChAdOx1, 4-28 d for Bell palsy July 2021
5 729 152 with BNT162b2, and
255 446 with mRNA-1273
Patone et al,9 Self-controlled Vaccinated individuals: 1-28 d UK December 2020- ChAdOx1 and GBS
2021 case series 20 417 752 with ChAdOx1 and May 2021
12 134 782 with BNT162b2
Hanson et al,10 Cohort study of Vaccinated individuals: 1-21 d vs US December 2020- Ad.26.COV2.S
2022 surveillance data 7 894 989; administered doses: 22-42 d November 2021 and GBS
483 053 Ad.26.COV2.S doses,
8 806 595 BNT162b2 doses, and
5 830 425 mRNA-1273 doses
Abara et al,11 US Vaccine Adverse Administered doses: 17 944 515 0-21 d; US December 2020- Ad26.COV2.S
2023 Event Reporting Ad26.COV2.S doses, 266 859 784 1-42 d January 2022 and GBS
System BNT162b2 doses, and
202 847 486 mRNA-1273 doses
García-Grimshaw Retrospective study of Administered doses: 81 842 426 0-42 d Mexico December 2020- Ad26.CoV2-S and
et al,12 2022 a nationwide registry ChAdOx1, rAd26-rAd5, October 2021 GBS; BNT162b2
Ad5-nCoV, Ad26.COV2.S, and GBS
mRNA-1273, BNT162b2, and
CoronaVac doses
Le Vu et al,13 Self-controlled Administered doses: 107 000 000 1-42 d France December 2020- ChAdOx1 and GBS;
2023 case series BNT162b2 doses, 23 000 000 May 2022 Ad26.COV2.S and
mRNA-1273 doses, 7.7 000 000 GBS
ChAdOx1 doses, and 1 000 000
Ad26.COV2.S doses
Osowicki et al,14 Enhanced Administered doses: 3 749 291 0-42 d Australia February 2021- ChAdOx1 and GBS
2022 spontaneous ChAdOx1 doses September 2021
surveillance system
following COVID-19
vaccination
Woo et al,15 2021 US Vaccine Adverse Administered doses: 13 209 858 1-21 d and US February 2021- Ad26.CoV2-S
Event Reporting Ad26.COV2.S doses 1-42 d July 2021 and GBS
System
Maramattom Observed cases Vaccinated individuals: 28 d India March-April 2021 ChAdOx1 and GBS
et al,16 2021 within 3 districts 1 200 000 with ChAdOx1
of Kerala, India
Li et al,17 2022 Population-based Vaccinated individuals: 0-21 d After UK and December 2020- No evidence
historical rate 4 376 535 with ChAdOx1, the first Spain May 2021 in of increased
comparison study 3 588 318 with BNT162b2, vaccine dose the UK and incidence
and self-controlled 244 913 with mRNA-1273, and December 2020-
case series 120 731 with Ad26.COV.2.S June 2021 in Spain
Keh et al,1 2023 National Administered doses: 20 300 000 Within 6 wk UK December 2021- ChAdOx1 and GBS
Immunoglobulin ChAdOx1 doses, 11 500 000 July 2021 for
Database BNT162b2 doses, and 300 000 retrospective data;
retrospective case mRNA-1273 doses January 2021-
identification and November 2021
prospective case for prospective
collection in UK data
multicenter
surveillance database

diagnoses) and study size; the latter is crucial in rare associations self-controlled English case series looking for GBS, transverse my-
where huge populations are required to identify low event num- elitis, and Bell palsy using a very similar (possibly the same) data set
bers reliably. coded in primary care from emergency department and secondary
institutions but using slightly different methodology included
UK 7 783 441 individuals vaccinated with ChAdOx1.8 New coded but
A UK self-controlled case series including unverified coding data of diagnostically unverified episodes of GBS logged from 4 to 42 days
hospital admissions assessed GBS incidence 1 to 28 days postvac- after vaccination were used in the analysis. A total of 517 cases of
cination. A total of 20 417 752 individuals vaccinated with a first dose GBS resulted in an increased post–ChAdOx1 vaccination IRR of 2.85
of ChAdOx1 were included. An increased incidence rate ratio (IRR) (95% CI, 2.33-3.47), corresponding to 11 excess cases of GBS per 1
for hospital admission or death due to GBS was reported from 15 to million vaccines. The excess was again after the first dose only, and
21 days (IRR, 2.90; 95% CI, 2.15-3.92) and 22 to 28 days (IRR, 2.21; the relative increase in GBS cases was highest among individuals aged
95% CI, 1.59-3.09) after vaccination. An increased risk of GBS in the 40 to 64 years.8 There was no association with the BNT162b2
1 to 28 days postvaccination (IRR, 2.04; 95% CI, 1.60-2.60) equated (BioNTech/Pfizer) vaccine.8
to an excess of 38 GBS cases per 10 million exposed to ChAdOx1.9 Significantly more reliable GBS diagnosis and case ascertain-
No association was demonstrable with BNT162b2. A Scottish ment using the UK National Immunoglobulin Database/NHSE IVIG
validation cohort supported these findings. 9 A subsequent database paired with known immunization type and date allowed

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 Clinical Review & Education Review SARS-CoV-2 Vaccination and Neuroimmunological Disease

for the evaluation of criteria-supported GBS diagnosis in relation to patients had facial weakness or paralysis in addition to limb weak-
20 300 000 ChAdOx1 doses, 11 500 000 of BNT162b2 doses, and ness, and Hanson et al10 suggested that AV vaccines may precipi-
300 000 mRNA-1273 (Moderna) doses.1 Only 90 to 140 excess UK tate a form of GBS that has distinct facial involvement. This was not
GBS cases above the background rate could be identified, distrib- borne out in practice or other larger more reliable series. The slightly
uting in a peak about 24 days after a first dose of the ChAdOx1 larger VAERS reported a small but statistically significant safety con-
vaccine.1 The excess risk of GBS in the first 42 days following vacci- cern for GBS following Ad26.COV2.S vaccination.15 The estimated
nation using ChAdOx1 was 0.576 cases (95% CI, 0.481-0.691) per crude reporting rate was 1 case of GBS per 100 000 doses of
100 000 doses, and this risk is established with higher certainty from Ad26.COV2.S. Woo et al15 calculated in the worst-case-scenario
this study. Using a prospective case collection in a multicenter UK analysis that the estimated absolute rate increase of GBS was 6.36
surveillance database, no specific vaccine-associated GBS pheno- per 100 000 person-years following Ad26.COV2.S vaccination. From
type was identified, illustrating how hard it is to identify cases with these small studies, neither the high incidence of facial paralysis nor
causal association from background occurrences.1 Tamborska et al18 GBS has occurred. A more recent publication from Abara et al11 also
also identified that ChAdOx1 may be associated with GBS using an used VAERS to identify GBS cases among 487 651 785 SARS-CoV-2
independent online open-access passive reporting national surveil- vaccine doses (17 944 515 Ad26.COV2.S doses, 266 859 784
lance system, but it should be noted that the the cases in their study BnT162b2 doses, and 202 847 486 mRNA-1273 doses) within 21 days
are a subset of those in the study by Keh et al.1 and 42 days of vaccination. The data indicated an association be-
tween Ad26.COV2.S and an increased risk of GBS (observed-to-
Germany expected [OE] ratio at 21 days, 3.79; 95% CI, 2.88-4.88; OE ratio at
Cases of GBS occurring between 3 and 42 days postvaccination re- 42 days, 2.34; 95% CI, 1.83-2.94), which was not observed for the
ported to the German national surveillance system were analyzed.19 mRNA vaccines (OE ratio less than 1 for both mRNA vaccines).11
Following vaccination with ChAdOx1 and Ad.26.COV2.S, the ex-
pected number of GBS cases was exceeded by a factor of 3.1 and 4.2, Mexico
respectively. This was not observed for messenger RNA (mRNA) vac- Mexico administered 81 842 426 doses of ChAdOx1, rAd26-rAd5
cines or for the additionally included influenza vaccine. Lehmann (Sputnik V, AV vaccine), Ad5-nCoV (Convidecia, AV vaccine),
et al19 also suggested a higher frequency of bilateral facial paresis Ad26.COV2.S, mRNA-1273, BNT162b2, and CoronaVac (Sinovac,
in GBS cases occurring after vaccination; however, acquisition may inactivated whole virus). Using CoronaVac as a comparator, higher
have been overestimated by the inclusion of Bell phenomenon (nor- incidences of GBS per 1 000 000 administered doses were ob-
mal upward elevation of the ocular globe on voluntary eye closure) served among those vaccinated with Ad26.COV2.S (3.86; 95% CI,
as well as Bell palsy and its synonyms as a search criterion for iden- 1.50-9.93) and BNT162b2 (1.92; 95% CI, 1.36-2.71).12 GBS incidence
tifying cases. per 1 000 000 administered doses was higher among mRNA-
based vaccine recipients in this cohort (1.85; 95% CI, 1.33-2.57). This
France is the only study to suggest a risk from BNT162b2, but it is one of
Using data from the French national health data system (Système the largest population studies reported.
National des Données de Santé), with 139 million doses of 4 vaccin-
ees (BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S), an ex- Australia
cess of approximately 6 cases of GBS per million persons occurred In Victoria, Australia, an enhanced passive (spontaneous) and
within 42 days of the first dose of each of the AV vaccines.13 There active surveillance system was used to identify GBS cases follow-
was no evidence of an increased risk after the second or third doses. ing vaccination against SARS-CoV-2. Within 42 days of vaccination,
An increased risk following Ad26.COV2.S was only observed in the observed GBS incidence rate was 1.85 per 100 000 doses of
individuals 50 years or older. This cohort only included cases of GBS ChAdOx1 following the first dose, with the expected rate given as
for patients requiring hospitalization, possibly underestimating 0.39 presentations per 100 000 adult population.14 The rate was
the true incidence. not increased for BNT162b2 or mRNA-1273.

US India
US reporting systems are smaller in size compared with the UK, as Maramattom et al16 reported a case series in which they observed
they frequently rely on insurance-based monitoring, as no true a 1.4-fold to 10-fold increase in the incidence of GBS during a 4-week
nationwide systems exist. Hanson et al10 performed a cohort study period between mid-March to mid-April 2021 in 3 districts of
of surveillance data (Vaccine Safety Datalink) from 7 894 989 indi- Kerela, India. The number of individuals in this cohort was esti-
viduals. An increased incidence of GBS following the Ad.26.COV2.S mated at only 1.2 million. In the UK, Singapore, and other countries
AV vaccine (only 483 053 doses) was observed in this cohort cal- with comprehensive pre–COVID-19 pandemic reporting of GBS
culated from the 11 reported and confirmed GBS cases following this cases, the case numbers remained largely the same as pre–
vaccine. The unadjusted incidence rate of GBS cases per 100 000 COVID-19 pandemic, and reported significant increases in cases in
person-years (32.4; 95% CI, 14.8-61.5) in the 1 to 21 days following small series is probably artifactual.
vaccination was highest in the first 14 days. This figure is 15-fold to
30-fold the background GBS rate10; subsequent cases of GBS that South Korea
have clearly not occurred at this frequency in larger vaccinated co- Lee et al20 performed a nationwide time series correlation study
horts and overestimated risk illustrates the problems of small stud- using data collected from the National Health Insurance Service and
ies with low event numbers. As a further illustration of this, 91% of Korea Disease Control and Prevention Agency databases to assess

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 SARS-CoV-2 Vaccination and Neuroimmunological Disease Review Clinical Review & Education

Figure 2. Excess Cases of Guillain-Barré Syndrome per 100 000 Adenoviral Vector (AV) Vaccines

Source Vaccine studied

Le Vu et al,14 2023 ChAdOx1, first dose, and
Ad26.COV2.S, first dose
Woo et al,16 2021 Ad26.COV2.S
Walker et al,9 2022 ChAdOx1
Abara et al,12 2023 Ad26.COV2.S
Patone et al,10 2021 ChAdOx1, first dose
Li et al,18 2022 ChAdOx1, first dose
Maramattom et al,17 2021 ChAdOx1, first dose
Osowicki et al,15 2022 ChAdOx1
Hanson et al,11 2022 Ad26.COV2.S, first dose
Keh et al,1 2022 ChAdOx1, first dose

0 1 2 3 4
Excess cases per 100 000 AV vaccines

The forest plot was created using data hand-extracted from 9 articles that for example, only the total number of Guillain-Barré syndrome cases for a given
recorded cases of Guillain-Barré syndrome following an AV vaccine, the vaccine with no expected or background rate available or without the total
background incidence in their cohort—or where the background incidence could number of individuals vaccinated using a specific vaccine. The excess cases
be taken from another cohort, which was possible for the British data—and the per 100 000 vaccines and the 95% CIs were calculated from the number of
number of vaccinated individuals for that specific vaccine. Articles containing vaccinated individuals for a given vaccine as well as the number of excess
Guillain-Barré syndrome data not included in the plot did not include the Guillain-Barré syndrome cases in that population. All the articles identified
parameters needed to calculate the excess cases per 100 000 vaccines, an excess of GBS cases following AV vaccination.

incidence of GBS prior to and during the COVID-19 pandemic. The (Figure 2).1,8-11,13-17 The data demonstrate a relatively equivalent
cumulative incidence rate of GBS was significantly lower during the number of cases of excess GBS per 100 000 vaccinations using AV
COVID-19 pandemic (2.1 per 100 000 population in 2020 to 2021 vaccines. One limitation of this graph is that the observed postvac-
vs 2.4 per 100 000 population in 2017 to 2019), but time series cor- cination time period varies as follows: Keh et al,1 42 days; Hanson
relation analysis demonstrated a strongly positive temporal asso- et al,10 21 days; Osowicki et al,14 28 days; Maramattom et al,16 28
ciation between SARS-CoV-2 vaccination and GBS in 2021. Lee et al20 days; Li et al,17 21 days; Patone et al,9 28 days; Abara et al,11 42 days;
did not specifically assess whether this could be attributed to a single Walker et al,8 4 to 42 days; Woo et al,15 42 days; and Le Vu et al,13
vaccine. In a prospective surveillance study including 38 828 691 total 42 days.
vaccine doses, of which 6 465 097 were AV vaccines (ChAdOx1 and
Ad26.CoV2.S), Ha et al21 concluded AV vaccines were associated with Bell Palsy
a 3-fold to 4-fold increased risk of developing GBS than mRNA vac- Studies including millions of vaccines or vaccinated individuals have
cines in the same cohort, with GBS following the AV vaccine asso- been included (Table 2).8,9,17,24 The unilateral lower motor neuron
ciated with the first dose.21 facial nerve palsy, often referred to as Bell palsy, describes paralysis
of the facial nerve that occurs in the absence of an identifiable cause,
International (Mixed Countries) with an annual incidence of 15 to 30 per 100 000 persons.25 The
Li et al17 evaluated 4 376 535 ChAdOx1, 3 588 318 BNT162b2, 244 913 phase 3 clinical trials of the mRNA vaccines identified a numerical
mRNA-1273, and 120 731 Ad26.CoV2 vaccinated individuals com- imbalance between Bell palsy occurrence in the vaccinated
pared with a historical cohort of 14 330 080 individuals in the gen- group compared with placebo, which instigated investigation into
eral populations of the UK and Spain. The authors did not identify whether there was an association of Bell palsy with SARS-CoV-2
an increased risk of GBS following any vaccine 0 to 21 days after the vaccination.26,27 This safety signal concern raised from the mRNA
first dose. Using the World Health Organization global pharmacovigi- vaccine clinical trials was investigated in a disproportionality analy-
lance database (VigiBase), Kim et al22 also found no association be- sis using the World Health Organization VigiBase, and the report-
tween GBS and SARS-CoV-2 vaccination compared with the influ- ing rate of facial paralysis was not found to be higher than that
enza vaccines but warned regarding the heterogeneity of sources observed with other vaccines.28 This finding of no association was
of information in the database. However, a further case report from supported by an interim analysis of surveillance data from 6.2 mil-
VigiBase suggested that there is a risk of GBS following AV vaccines.23 lion individuals in the US vaccinated with 11.8 million doses of mRNA
vaccine.29 However, following separate, independent analyses of
Summary of GBS Data the clinical trial data, Cirillo and Doan30 and Ozonoff et al31 both sug-
The 4 UK studies highlight the major difficulties of the rush to study gested a higher risk of developing facial palsy associated with the
and, subsequently, of any systematic synthesis. Estimates of risk were mRNA vaccines compared with the background population. A safety
generated with differing reliability, and for any future synthesis, sig- assessment by Sato et al32 using the VAERS database then demon-
nificant numbers of the cases in these 4 studies are likely the same strated that the incidence of Bell palsy following SARS-CoV-2 vac-
case reported multiple times but with variable diagnostic certainty. cination was lower than or equivalent to the rates associated with
We calculated and demonstrated the excess number of cases of GBS influenza vaccines; however, there was a statistically significant
per 100 000 vaccines for 10 studies that evaluated AV vaccines relationship between SARS-CoV-2 vaccination and BNT162b2 or

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 Clinical Review & Education Review SARS-CoV-2 Vaccination and Neuroimmunological Disease

Table 2. Association Between Vaccination and Bell Palsy

Vaccinated individuals/ Postvaccination risk Period of Possible
Source Study type administered doses, No. window of interest Country data collection associations
Walker et al,8 Self-controlled Vaccinated individuals: 7 783 441 with 4-42 d for GBS; 4-28 d UK July 2020- ChAdOx1 and
2022 case series ChAdOx1, 5 729 152 with BNT162b2, for Bell palsy July 2021 Bell palsy
and 255 446 with mRNA-1273
Patone et al,9 Self-controlled Vaccinated individuals: 20 417 752 with 1-28 d UK December 2020- ChAdOx1 and
2021 case series ChAdOx1 and 12 134 782 with May 2021 Bell palsy
BNT162b2
Shibli et al,24 Retrospective Administered doses: 2 594 990 first Within 21 d of the first Israel December 2020 BNT162b2 and
2021 cohort study with doses and 2 434 674 second doses vaccine and 30 d of the (first dose) and Bell palsy
noncurrent historic of BNT162b2 second vaccine January 2021
comparative group (second dose)-
April 2021,
followed until
May 2021
Li et al,17 Population-based Vaccinated individuals: 4 376 535 with 0-21 d After the first UK and December 2020- No evidence
2022 historical rate ChAdOx1, 3 588 318 with BNT162b2, vaccine dose Spain May 2021 of increased
comparison study 244 913 with mRNA-1273, and 120 731 in the UK and incidence
and self-controlled with Ad26.COV.2 December 2020-
case series June 2021 in
Spain

mRNA-1273 vaccination above the background prevalence.32 An im- of the COVID-19 pandemic and the inherent complexity of autoim-
portant major flaw in the data is the inclusion of Bell phenomenon munity, finding an autoimmunity and SARS-CoV-2 link will be chal-
in the search criteria.33 A full analysis of the articles evaluating the lenging. It does not appear that the spike protein is a causal trigger
association between Bell palsy and vaccination is available in of autoimmunity; if it were, then autoimmune diseases and GBS would
eMethods 2 in the Supplement. In summary, an association of occur with equal frequency in all vaccines. Repeated stimulation of
vaccination with Bell palsy is unclear. C57B1/6 mice with recombinant SARS-CoV-2 spike protein does not
induce any measurable autoimmunity.36 It follows that the vaccine
Myasthenia Gravis, Multiple Sclerosis and Central component common to the AV vaccines is the stimulus associated
Demyelination, Neuromyelitis Optica Spectrum Disorders, with the development of GBS. Despite the likelihood that AV com-
and Myelin Oligodendrocyte Glycoprotein ponents are the causative stimulus, it is then unclear if it is the in-
Antibody–Associated Disease flammatory response to the vaccination, host genetic factors such
An association between vaccination and myasthenia gravis, multiple as HLA haplotypes, autoreactivity of the adenovirus particles, or any
sclerosisandcentraldemyelination,neuromyelitisopticaspectrumdis- or all of these could therefore be involved in the pathogenesis of GBS.
orders, and myelin oligodendrocyte glycoprotein antibody–associated Identified adenoviral infection does not classically precede GBS
disease occurrence is not clearly supported by the literature. A detailed onset in a frequency higher than background rates of infection and
analysis is included in eMethods 2 in the Supplement. has not often been linked to GBS pathogenesis.37 One study stands
out as finding very high seroconversion rates,38 but this finding has
never been replicated. The adenoviral serotypes used in vaccina-
tions are deliberately selected for their low virulence in humans. AV
Discussion
vaccines, in part due to the broad tissue tropism of adenovirus, are
GBS remains the neurological condition with the clearest evidence nonetheless potently immunogenic. The ChAdOx1 vaccine is based
of a causal link with SARS-CoV-2 vaccination. However, neither SARS- on the chimpanzee adenovirus (ChAd) Y25, and Ad26.COV2.S is
CoV-2 nor adenoviruses have been convincingly associated with GBS based on species D human adenovirus serotype 26 (Ad26). Ad26
pathogenesis. Whether the vaccine data indicate that adenovirus has a low seroprevalence in humans,39 and a notable benefit to using
may be of undetermined pathogenic importance in GBS is unclear,34 ChAds is also the circumventing of any more generic preexisting hu-
but it would not be impossible. Discussion of the underlying patho- man adenoviral immunity in the general population; the presence
genesis of AV vaccine–driven GBS remains purely hypothetical of antibodies against a given adenovirus serotype would greatly
owing to rarity, unstructured case ascertainment, and absence of impede the immunogenicity of the vaccine antigen.40 Whether this
widespread clinical biomarker sampling. potent and distinctive immunogenicity of AV vaccination could be
Identifying the molecular agent driving autoimmunity aids in any linked to driving autoimmunity through, for example, activating
discussion of pathogenesis. This concerns some or all of the spike pro- anergic B cells or activation of bystander T cells in susceptible indi-
tein, the AV components, and the immune response to vaccination viduals is pure speculation.41,42 To our knowledge, both processes
or infection. The autoimmune diseases that are reported to have yet to be associated with GBS. In addition, while there have
occur following COVID-19 only very rarely involve the peripheral ner- been no known genetic associations when studying GBS as a group,
vous system.35 The studies and data suggesting an association be- there is little known about individual precipitating infections for
tween SARS-CoV-2 infection and self-reactivity are dependent on HLA linkage, for example. Further investigation of this topic could
temporal associations and have little else to support a proven aim to identify distinctive antibody or T-cell receptor signatures to
causality.35 Unlike vaccination, it is difficult to pinpoint an infection AV fragments in individuals with post–AV vaccine GBS compared with
date or time of immune response in infection adding additional unaffected AV vaccine–immunized controls, a unique HLA haplo-
uncertainty to coassociation. Given the unprecedented conditions type in those with post–AV vaccine GBS compared with controls, or

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 SARS-CoV-2 Vaccination and Neuroimmunological Disease Review Clinical Review & Education

specific neural/myelin-centric molecular targets for AV antibodies of large cohorts convincingly reproduced consistent similar numeri-
in those with post–AV vaccine GBS. cal associations for the AV-based ChAdOx1 vaccine, and these have
The occurrence of VITT following vaccination with ChAdOx and been replicated in other international studies. The risk of Bell palsy
Ad26.COV2.S has a clearer pathomechanism.43 VITT is estimated to following SARS-CoV-2 vaccination was unclear. No quantifiable
occur in 3 to 15 persons per million first doses of AV vaccine, with some excess risk was identified for myasthenia gravis, multiple sclerosis,
rare cases occurring after a second vaccination. Biomarkers such as or neuromyelitis optica spectrum disorders.
thrombocytopenia, D-dimer elevation, and reduced plasma fibrino- There are substantial confounding factors in all of the studies,
gen were identified in many cases. VITT was also associated with im- limiting the certainty of their conclusions. Vaccination of a substan-
munoglobulin G antibodies directed against platelet factor 4, which tial proportion of the world’s population happened after a year of
leads to greatly enhanced platelet activation.44 Whether cross- severe pandemic illness and restricted interperson mixing, with back-
reactivity of AV components and peripheral nerve (glyco-)proteins ground health and environmental risk substantially modifying health
could similarly lead to GBS has been suggested in the literature. How- and immune exposures. The global search for a vaccine solution was
ever, the electrostatic interaction of platelet factor 4 that initiates met in many quarters by suspicion and criticism of new technol-
VITT is not easily replicated by peripheral nerve components. ogy. There were many motivations for physicians, the public, and
Further research is needed to investigate the cross-reactivity of politicians to report any perceived complication. The lack of many
antibodies against different vectors after immunization as well as organized, effective, and highly accurate national surveillance sys-
the possible interaction between components of adenoviruses and tems was quickly realized, and the data generated by multiple,
surface molecules of peripheral nerve structures. heterogeneous acquisition and diagnosis-based systems are of ques-
tionable certainty for these rare and difficult-to-diagnose events.
It is very unlikely that the risks of vaccination for any associated con-
dition have been underestimated. But it is very clear that the reduc-
Conclusions
tions in illness episodes, hospitalizations, and deaths were the
In this review, we found there was a small increased risk of GBS result of the huge, conferred benefits of SARS-CoV-2 vaccination at
following AV-based SARS-CoV-2 vaccines. High-quality UK studies the individual and societal levels.45

ARTICLE INFORMATION outside the submitted work. Dr Meuth reported Front Public Health. 2020;8:361. doi:10.3389/
Accepted for Publication: November 10, 2023. personal fees from Academy 2, Argenx, Alexion, fpubh.2020.00361
Almirall, Amicus Therapeutics Germany, Bayer 3. Kerr S, Joy M, Torabi F, et al. First dose ChAdOx1
Published Online: January 16, 2024. Health Care, Biogen, BioNTech, Bristol Myers
doi:10.1001/jamaneurol.2023.5208 and BNT162b2 COVID-19 vaccinations and cerebral
Squibb, Celgene, Datamed, Demecan, Desitin, venous sinus thrombosis: a pooled self-controlled
Author Affiliations: Department of Neurology, Diamed, Diaplan, DIU Dresden, DPmed, Genzyme, case series study of 11.6 million individuals in
University Hospital Düsseldorf, Medical Faculty, Hexal AG, Impulze GmbH, Janssen Cilag, KW England, Scotland, and Wales. PLoS Med. 2022;19
Heinrich Heine University, Düsseldorf, Germany Medipoint, MedDay Pharmaceuticals, Merck (2):e1003927. doi:10.1371/journal.pmed.1003927
(A. G. Willison, Pawlitzki, Hartung, Meuth); Centre Serono, MICE, Mylan, Neuraxpharm, Neuropoint,
for Neuromuscular Disease, National Hospital for Novartis, Novo Nordisk, ONO Pharma, Oxford 4. Whiteley WN, Ip S, Cooper JA, et al;
Neurology and Neurosurgery, Queen Square, PharmaGenesis, Roche, Sanofi-Aventis, Springer CVD-COVID-UK consortium. Association of
London, United Kingdom (Lunn); Department of Medizin Verlag, STADA, Chugai Pharma, COVID-19 vaccines ChAdOx1 and BNT162b2 with
Neuromuscular Disease, Institute of Neurology, QuintilesIMS, Teva, Wings for Life International, and major venous, arterial, or thrombocytopenic
University College London, London, United Xcenda as well as grants from the German Ministry events: a population-based cohort study of 46
Kingdom (Lunn); College of Medicine, Veterinary for Education and Research (BMBF), Bundesinstitut million adults in England. PLoS Med. 2022;19(2):
and Life Sciences, University of Glasgow, Glasgow, für Risikobewertung (BfR), Deutsche e1003926. doi:10.1371/journal.pmed.1003926
United Kingdom (H. J. Willison); Department of Forschungsgemeinschaft (DFG), Else Kröner 5. Willison HJ, Jacobs BC, van Doorn PA.
Neurology, Medical University of Vienna, Vienna, Fresenius Foundation, Gemeinsamer Guillain-Barré syndrome. Lancet. 2016;388
Austria (Hartung); Brain and Mind Center, Bundesausschuss (G-BA), German Academic (10045):717-727. doi:10.1016/S0140-6736(16)
University of Sydney, Sydney, Australia (Hartung); Exchange Service, Hertie Foundation, 00339-1
Department of Neurology, Palacky University, Interdisciplinary Center for Clinical Studies (IZKF) 6. Sejvar JJ, Baughman AL, Wise M, Morgan OW.
Olomouc, Czech Republic (Hartung). Munster, German Foundation Neurology, Alexion, Population incidence of Guillain-Barré syndrome:
Author Contributions: Drs Willison and Pawlitzki Almirall, Amicus Therapeutics Germany, Biogen, a systematic review and meta-analysis.
were co–first authors. Drs Hartung and Meuth were Diamed, Deutsche Gesellschaft für Materialkunde Neuroepidemiology. 2011;36(2):123-133.
co–senior authors. (DGM), Fresenius Medical Care, Genzyme, doi:10.1159/000324710
Gesellschaft von Freunden und Förderern der
Conflict of Interest Disclosures: Dr A. Willison Heinrich-Heine-Universität Düsseldorf, HERZ 7. Breman JG, Hayner NS. Guillain-Barré syndrome
reported personal fees from Merck, Sanofi Aventis, Burgdorf, Merck Serono, Novartis, ONO Pharma, and its relationship to swine influenza vaccination
and Novartis outside the submitted work. Roche, and Teva outside the submitted work. in Michigan, 1976-1977. Am J Epidemiol. 1984;119
Dr Pawlitzki reported personal fees from Argenx, No other disclosures were reported. (6):880-889. doi:10.1093/oxfordjournals.aje.a113810
Alexion, Hexal, Janssen, Merck, Novartis, Bayer, 8. Walker JL, Schultze A, Tazare J, et al. Safety of
and Biogen outside the submitted work. REFERENCES COVID-19 vaccination and acute neurological
Dr H. Willison reported grants from Argenx and events: a self-controlled case series in England
Annexon Biosciences as well as personal fees from 1. Keh RYS, Scanlon S, Datta-Nemdharry P, et al;
BPNS/ABN COVID-19 Vaccine GBS Study Group. using the OpenSAFELY platform. Vaccine. 2022;40
Argenx, AOA Dx, AstraZeneca, Boehringer (32):4479-4487. doi:10.1016/j.vaccine.2022.06.010
Ingelheim, Coronex, CSL, Gene Tx Therapeutics, COVID-19 vaccination and Guillain-Barré syndrome:
GSK, Hoffman La Roche, Immunic Therapeutics, analyses using the National Immunoglobulin 9. Patone M, Handunnetthi L, Saatci D, et al.
Longboard Pharma, Novartis, UCB Biopharma SRL, Database. Brain. 2023;146(2):739-748. Neurological complications after first dose of
and Annexon Biosciences outside the submitted doi:10.1093/brain/awac067 COVID-19 vaccines and SARS-CoV-2 infection.
work. Dr Hartung reported personal fees from 2. Principi N, Esposito S. Do vaccines have a role as Nat Med. 2021;27(12):2144-2153. doi:10.1038/
Horizon Therapeutics, Merck, Novartis, and Roche a cause of autoimmune neurological syndromes? s41591-021-01556-7

jamaneurology.com (Reprinted) JAMA Neurology February 2024 Volume 81, Number 2 185

© 2024 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Stephen Arbeit on 03/04/2024
 Clinical Review & Education Review SARS-CoV-2 Vaccination and Neuroimmunological Disease

10. Hanson KE, Goddard K, Lewis N, et al. 21. Ha J, Park S, Kang H, et al. Real-world data on Self-Reporting Database” by Sato et al. Int J Infect Dis.
Incidence of Guillain-Barré syndrome after the incidence and risk of Guillain-Barré syndrome 2022;116:10. doi:10.1016/j.ijid.2021.12.346
COVID-19 vaccination in the Vaccine Safety following SARS-CoV-2 vaccination: a prospective 34. Lunn MP. Guillain-Barré syndrome in an era of
Datalink. JAMA Netw Open. 2022;5(4):e228879. surveillance study. Sci Rep. 2023;13(1):3773. global infections and 21st century vaccination. Curr
doi:10.1001/jamanetworkopen.2022.8879 doi:10.1038/s41598-023-30940-1 Opin Neurol. 2022;35(5):571-578. doi:10.1097/WCO.
11. Abara WE, Gee J, Marquez P, et al. Reports of 22. Kim JE, Park J, Min YG, Hong YH, Song TJ. 0000000000001086
Guillain-Barré syndrome after COVID-19 vaccination Associations of Guillain-Barré syndrome with 35. Sharma C, Bayry J. High risk of autoimmune
in the United States. JAMA Netw Open. 2023;6(2): coronavirus disease 2019 vaccination: diseases after COVID-19. Nat Rev Rheumatol. 2023;
e2253845. doi:10.1001/jamanetworkopen.2022. disproportionality analysis using the World Health 19(7):399-400. doi:10.1038/s41584-023-00964-y
53845 Organization pharmacovigilance database.
J Peripher Nerv Syst. 2022;27(3):206-214. 36. Scherlinger M, Sibilia J, Tsokos GC, Gottenberg
12. García-Grimshaw M, Galnares-Olalde JA, JE. Chronic stimulation with SARS-CoV-2 spike
Bello-Chavolla OY, et al. Incidence of Guillain-Barré doi:10.1111/jns.12507
protein does not trigger autoimmunity. Clin Immunol.
syndrome following SARS-CoV-2 immunization: 23. Atzenhoffer M, Auffret M, Pegat A, et al. 2023;248:109264. doi:10.1016/j.clim.2023.109264
analysis of a nationwide registry of recipients of 81 Guillain-Barré syndrome associated with COVID-19
million doses of seven vaccines. Eur J Neurol. 2022; vaccines: a perspective from spontaneous report 37. Jacobs BC, Rothbarth PH, van der Meché FG,
29(11):3368-3379. doi:10.1111/ene.15504 data. Clin Drug Investig. 2022;42(7):581-592. et al. The spectrum of antecedent infections in
doi:10.1007/s40261-022-01164-4 Guillain-Barré syndrome: a case-control study.
13. Le Vu S, Bertrand M, Botton J, et al. Risk of Neurology. 1998;51(4):1110-1115. doi:10.1212/
Guillain-Barré syndrome following COVID-19 24. Shibli R, Barnett O, Abu-Full Z, et al. Association WNL.51.4.1110
vaccines: a nationwide self-controlled case series between vaccination with the BNT162b2 mRNA
study. Neurology. 2023;101(21):e2094-e2102. COVID-19 vaccine and Bell’s palsy: 38. Terryberry JW, Thor G, Peter JB.
doi:10.1212/WNL.0000000000207847 a population-based study. Lancet Reg Health Eur. Autoantibodies in neurodegenerative diseases:
2021;11:100236. doi:10.1016/j.lanepe.2021.100236 antigen-specific frequencies and intrathecal
14. Osowicki J, Morgan HJ, Harris A, et al; SAEFVIC analysis. Neurobiol Aging. 1998;19(3):205-216.
and VicSIS investigators. Guillain-Barré syndrome 25. Tiemstra JD, Khatkhate N. Bell’s palsy: doi:10.1016/S0197-4580(98)00049-9
temporally associated with COVID-19 vaccines in diagnosis and management. Am Fam Physician.
Victoria, Australia. Vaccine. 2022;40(52):7579-7585. 2007;76(7):997-1002. 39. Geisbert TW, Bailey M, Hensley L, et al.
doi:10.1016/j.vaccine.2022.10.084 Recombinant adenovirus serotype 26 (Ad26) and
26. Baden LR, El Sahly HM, Essink B, et al; COVE Ad35 vaccine vectors bypass immunity to Ad5 and
15. Woo EJ, Mba-Jonas A, Dimova RB, Study Group. Efficacy and safety of the mRNA-1273 protect nonhuman primates against ebolavirus
Alimchandani M, Zinderman CE, Nair N. Association SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5): challenge. J Virol. 2011;85(9):4222-4233.
of receipt of the Ad26.COV2.S COVID-19 vaccine 403-416. doi:10.1056/NEJMoa2035389 doi:10.1128/JVI.02407-10
with presumptive Guillain-Barré syndrome, 27. Polack FP, Thomas SJ, Kitchin N, et al;
February-July 2021. JAMA. 2021;326(16):1606-1613. 40. Ewer K, Sebastian S, Spencer AJ, Gilbert S, Hill
C4591001 Clinical Trial Group. Safety and efficacy of AVS, Lambe T. Chimpanzee adenoviral vectors as
doi:10.1001/jama.2021.16496 the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. vaccines for outbreak pathogens. Hum Vaccin
16. Maramattom BV, Krishnan P, Paul R, et al. 2020;383(27):2603-2615. doi:10.1056/ Immunother. 2017;13(12):3020-3032. doi:10.1080/
Guillain-Barré syndrome following NEJMoa2034577 21645515.2017.1383575
ChAdOx1-S/nCoV-19 vaccine. Ann Neurol. 2021;90 28. Renoud L, Khouri C, Revol B, et al. Association
(2):312-314. doi:10.1002/ana.26143 41. Shim CH, Cho S, Shin YM, Choi JM. Emerging
of facial paralysis with mRNA COVID-19 vaccines: role of bystander T cell activation in autoimmune
17. Li X, Raventós B, Roel E, et al. Association a disproportionality analysis using the World Health diseases. BMB Rep. 2022;55(2):57-64. doi:10.5483/
between COVID-19 vaccination, SARS-CoV-2 Organization Pharmacovigilance Database. JAMA BMBRep.2022.55.2.183
infection, and risk of immune mediated Intern Med. 2021;181(9):1243-1245. doi:10.1001/
neurological events: population based cohort and jamainternmed.2021.2219 42. Tanaka S, Ise W, Baba Y, Kurosaki T. Silencing
self-controlled case series analysis. BMJ. 2022;376: and activating anergic B cells. Immunol Rev. 2022;
29. Klein NP, Lewis N, Goddard K, et al. 307(1):43-52. doi:10.1111/imr.13053
e068373. doi:10.1136/bmj-2021-068373 Surveillance for adverse events after COVID-19
18. Tamborska AA, Singh B, Leonhard SE, et al; UK mRNA vaccination. JAMA. 2021;326(14):1390-1399. 43. Baker AT, Boyd RJ, Sarkar D, et al. ChAdOx1
Covid Vaccine GBS Study Group. Guillain-Barré doi:10.1001/jama.2021.15072 interacts with CAR and PF4 with implications for
syndrome following SARS-CoV-2 vaccination in the thrombosis with thrombocytopenia syndrome. Sci
30. Cirillo N, Doan R. Bell’s palsy and SARS-CoV-2 Adv. 2021;7(49):eabl8213. doi:10.1126/sciadv.abl8213
UK: a prospective surveillance study. BMJ Neurol vaccines-an unfolding story. Lancet Infect Dis. 2021;
Open. 2022;4(2):e000309. doi:10.1136/bmjno-2022- 21(9):1210-1211. doi:10.1016/S1473-3099(21)00273-5 44. Greinacher A, Schönborn L, Siegerist F, et al.
000309 Pathogenesis of vaccine-induced immune
31. Ozonoff A, Nanishi E, Levy O. Bell’s palsy and thrombotic thrombocytopenia (VITT). Semin
19. Lehmann HC, Oberle D, Keller-Stanislawski B, SARS-CoV-2 vaccines. Lancet Infect Dis. 2021;21(4):
Rieck T, Streit R. Rare cases of Guillain-Barré Hematol. 2022;59(2):97-107. doi:10.1053/
450-452. doi:10.1016/S1473-3099(21)00076-1 j.seminhematol.2022.02.004
syndrome after COVID-19 vaccination, Germany,
December 2020 to August 2021. Euro Surveill. 32. Sato K, Mano T, Niimi Y, Toda T, Iwata A, 45. Doneddu PE, Spina E, Briani C, Fabrizi GM,
2023;28(24):2200744. doi:10.2807/1560-7917.ES. Iwatsubo T. Facial nerve palsy following the Manganelli F, Nobile-Orazio E; Italian Peripheral
2023.28.24.2200744 administration of COVID-19 mRNA vaccines: Nervous System Association (ASNP). Acute and
analysis of a self-reporting database. Int J Infect Dis. chronic inflammatory neuropathies and COVID-19
20. Lee H, Heo N, Kwon D, Ha J. Deciphering 2021;111:310-312. doi:10.1016/j.ijid.2021.08.071
changes in the incidence of the Guillain-Barré vaccines: practical recommendations from the task
syndrome during the COVID-19 pandemic: 33. O’Fee JR, Li J, Chang JR. Response to “Facial force of the Italian Peripheral Nervous System
a nationwide time-series correlation study. BMJ Nerve Palsy Following the Administration of Association (ASNP). J Peripher Nerv Syst. 2021;26
Neurol Open. 2022;4(2):e000378. doi:10.1136/ COVID-19 mRNA Vaccines: Analysis of a (2):148-154. doi:10.1111/jns.12435
bmjno-2022-000378

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