AbstractSince coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain–Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most findings were reported in the form of case reports or case series, whereas a comprehensive overview is still lacking. We conducted a systematic review and searched for all published cases until July 20th 2020. We included 73 patients reported in 52 publications. A broad age range was affected (mean 55, min 11–max 94 years) with male predominance (68.5%). Most patients showed respiratory and/or systemic symptoms, and developed GBS manifestations after COVID-19. However, asymptomatic cases for COVID-19 were also described. The distributions of clinical variants and electrophysi-ological subtypes resemble those of classic GBS, with a higher prevalence of the classic sensorimotor form and the acute inflammatory demyelinating polyneuropathy, although rare variants like Miller Fisher syndrome were also reported. Cer-ebrospinal fluid (CSF) albuminocytological dissociation was present in around 71% cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin. Patients with less favorable outcome were associated with a significantly older age in accordance with previous findings regarding both classic GBS and COVID-19. COVID-19-associated GBS seems to share most features of classic post-infectious GBS and possibly the same immune-mediated pathogenetic mechanisms. Nevertheless, more extensive epidemiological studies are needed to clarify these issues.
Coronavirus disease 2019 (COVID-19) pandemic has rap-idly spread around the world from Jan-2020, with more than 14,000,000 cases confirmed so far [1]. Although primary
affecting the respiratory system, central and peripheral neu-rological manifestations associated with severe acute respir-atory syndrome coronavirus 2 (SARS-CoV-2) infection have been increasingly reported [2–4]. In detail, several pieces of evidence suggested an association between SARS-CoV-2 infection and the development of Guillain–Barré Syndrome (GBS) [5–56].
GBS represents the most common cause of acute flac-cid paralysis [57]. The classic form is an immune-mediated acute-onset demyelinating polyradiculoneuropathy (acute inflammatory demyelinating polyneuropathy—AIDP) typi-cally presenting with ascending weakness, loss of deep ten-don reflexes, and sensory deficits. Diagnosis of GBS relies on the results of clinical, electrophysiological, and cerebro-spinal fluid (CSF) examinations (classically albuminocyto-logical dissociation) [57–59]. The clinical spectrum of GBS encompasses a classic sensorimotor form, Miller Fisher syn-drome (MFS), bilateral facial palsy with paraesthesia, pure
motor, pure sensory, paraparetic, pharyngeal–cervical–bra-chial variants, polyneuritis cranialis (GBS–MFS overlap), and Bickerstaff brainstem encephalitis [57–60]. As regard electrophysiological features, three main subtypes are rec-ognized: AIDP, acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN) [57, 58, 61]. Peripheral nerve damage is thought to be provoked by an aberrant immune response to infections, in some cases driven by the production of autoreactive antibodies (anti-ganglioside antibodies) [57–59]. Potential trigger-ing pathogens include both viruses [e.g., cytomegalovirus (CMV), Epstein–Barr virus (EBV), influenza virus, hepatitis E virus, and Zika virus] and bacteria (e.g., Campylobacter Jejuni, Mycoplasma Pneumoniae) [57, 58, 62]. However, a relationship with other events has been also described (e.g., vaccinations, surgery, administration of checkpoint inhibi-tors, and malignancy) [57, 58]. Given that a potential causal association with beta-coronaviruses [Middle East Respira-tory Syndrome (MERS-CoV)] has already been speculated, the relationship between COVID-19 and GBS deserves undoubtedly further attention [63, 64].
With this background, our systematic review aimed to provide a comprehensive and updated overview of all case reports and series of COVID-19-related GBS to identify pre-dominant clinical, laboratory, and neurophysiological pat-terns and to discuss the possible underlying pathophysiology.
Methods
We performed a systematic review according to the SALSA (Search, Appraisal, Synthesis, and Analysis) analytic frame-work [65]. We screened in PubMed and Google Scholar databases for all case descriptions of GBS associated with COVID-19 that were published from January 1st 2020 up to July 20th 2020. Keywords (including all commonly used abbreviations of these terms) used in the search strategy were as follows: [“acute autoimmune neuropathy” OR “acute inflammatory demyelinating polyneuropathy” OR “acute inflammatory demyelinating polyradiculoneuropathy,” OR “acute inflammatory polyneuropathy” OR “Demyelinating Polyradiculoneuropathy” OR “Guillain–Barre Syndrome” OR “Guillain–Barre” OR ““Miller–Fisher” OR “Bickerstaff encephalitis” OR “AIDP” OR “AMAN” OR “AMSAN” OR polyneuritis cranialis] AND [“COVID-19” OR “Wuhan coronavirus” OR “novel coronavirus” OR “novel corona-virus 2019” OR “SARS” OR “SARS-CoV-2”]. Suitable references were also identified in the authors’ archives of scientific literature on GBS. We restricted our search to stud-ies published in English, Spanish, or Italian. Publications that were not peer-reviewed were excluded from this study. PRISMA criteria were applied. For each case, we extracted data concerning demographic and clinical variables, results
of diagnostic investigations, and outcome. If the GBS clini-cal variant [57] or the electrophysiological subtype [61] was not explicitly reported in the paper, we reconstructed it, when possible, from reported details. We also classified the diagnostic certainty of all cases according to the Brighton Criteria [66]. Searches were performed by SAR, AA, and MF. The selection of relevant articles was shared with all authors.
For statistical analysis, we used IBM SPSS Statistics ver-sion 21 (IBM, Armonk, NY, USA). Based on the distribu-tion of values, continuous data were expressed as mean ± standard deviation or as median and interquartile range (IQR). Depending on the number of groups and data distri-bution, we applied the t test, the Mann–Whitney U test or the Kruskal–Wallis test (followed by Dunn–Bonferroni post hoc test). All reported p values were adjusted for multiple comparisons. We adopted the Chi-square test for categorical variables. Differences were considered statistically signifi-cant at p < 0.05.
For the present study, no authorization to an Ethics Com-mittee was asked, because the original reports, nor this work, provided any personal information of the patients.
Results
Our literature search identified 101 papers, including 37 case reports, 12 case series, 3 reviews with case reports, 42 reviews, 4 letters, 1 original article, 1 point of view, and 1 brief report. Four and one patients were excluded from the analysis because of a missing laboratory-proven SARS-CoV-2 infection or an ambiguous GBS diagnosis [disease course resembling chronic inflammatory demyelinating neu-ropathy (CIDP)], respectively. A total of 52 studies were included in the final analysis (total patients = 73) [5–56]. All data concerning the analyzed patients are reported in Table 1. For one case [20], most clinical and diagnostic details were not reported; therefore, many of our analyses were limited to 72 patients.
Epidemiological distribution and demographic characteristics of the patients
To date, GBS cases (n = 73) were reported from all conti-nents except Australia. In details, patients were originally from Italy (n = 20), Iran (n = 10), Spain (n = 9), USA (n = 8), United Kingdom (n = 5), France (n = 4), Switzerland (n = 4), Germany (n = 3), Austria (n = 1), Brazil (n = 1), Canada (n = 1), China (n = 1), India (n = 1), Morocco (n = 1), Saudi Arabia (n = 1), Sudan (n = 1), The Netherlands (n = 1), and Turkey (n = 1) (Table 1, Fig. 1). The mean age at onset was 55 ± 17 years (min 11–max 94), including four pediatric cases [21, 27, 35, 41]. A significative prevalence of men
1135Journal of Neurology (2021) 268:1133–1170
1 3
compared to women was noticed (50 vs. 23 cases: 68.5% vs. 31.5%) with no significant difference in age at onset between men and women (mean: 55 ± 18 vs. 56 ± 16 years, p = 0.643). Comorbidities were variably reported with no prevalence of a particular disease.
Clinical picture, diagnosis, and therapy of COVID‑19
All reported GBS cases (n = 72) except two were sympto-matic for COVID-19 with various severity. Most common manifestations of COVID-19 included fever (73.6%, 53/72), cough (72.2%, 52/72), dyspnea and/or pneumonia (63.8%, 46/72), hypo-/ageusia (22.2%, 16/72), hypo-/anosmia (20.8%, 15/72), and diarrhea (18.1%, 13/72). One of the two asymptomatic subjects never developed fever, respiratory symptoms, or pneumonia [10], whereas the other patient showed an asymptomatic pneumonia at chest computed tomography (CT) [12]. In all but six patients with available data [22, 24, 36, 44, 45, 52], SARS-CoV-2 RT-PCR with naso- or oropharyngeal swab or fecal exam was positive at first or following tests. Nevertheless, these six patients tested positive at SARS-CoV-2 serology. In four patients, the laboratory exam for the diagnostic confirmation was not specified [20, 40]. Typical “ground glass” aspects at chest-CT or similar findings at CT, Magnetic Resonance Imag-ing (MRI) or X-ray compatible with COVID-19 interstitial pneumonia were reported in 40 cases. The detailed therapies for COVID-19 are described in Table 1.
Clinical features of GBS spectrum
In all (n = 72) but four patients [10, 37, 40, 56], GBS manifes-tations developed after those of COVID-19 [median (IQR): 14 (7–20), min 2–max 33 days]. Differently, COVID-19 symptoms began concurrent in one case [37], 1 day [40] and 8 days [55] after GBS onset in two other cases and never developed in another one [10] (Table 1). Common clinical manifestations at onset included sensory symptoms (72.2%, 52/72) alone or in combination with paraparesis or tetrapa-resis (65.2%, 47/72, respectively). Cranial nerve involvement (e.g., facial, oculomotor nerves) was less frequently described at onset (16.7%, 12/72). Moreover, all cases but one [26] showed lower limbs or generalized areflexia, whereas in 37.5% (27/72) of the cases, gait ataxia was reported at onset or during the disease course. Even if ascending weakness evolving into flaccid tetraparesis (76.4%, 55/72) and spread-ing/persistence of sensory symptoms (84.7%, 61/72) repre-sented the most common clinical evolutions, 50.0% (36/72) and 23.6% (17/72) patients showed cranial nerve deficits and dysphagia, respectively, during disease course (Table 1). Moreover, 36.1% (26/72) of the patients developed respira-tory symptoms, and some of them evolved to respiratory fail-ure (Table 1). Autonomic disturbances were rarely reported
(16.7%, 12/72). In cases with MFS/MFS-GBS overlap, are-flexia, oculomotor disturbances, and ataxia were present in 100% (9/9), 66.7% (6/9) and 66.7% (6/9), respectively [8, 19, 23, 30, 32, 33, 43, 44]. The median of time to nadir was cal-culated in 40 patients with available data and resulted 4 days (IQR 3–9) (Table 1).
Results of electrophysiological, CSF, biochemical, and neuroimaging investigations
Detailed electroneurography results were reported in 84.9% (62/73) of the cases. Specifically, 77.4% (48/62) cases showed a pattern compatible with a demyelinating polyra-diculoneuropathy. In contrast, axonal damage was prominent in 14.5% (9/62). In a minority of the patients (8.1%), a mixed pattern was reported (5/62). Regarding CSF analysis (full results were available in 59 out of 73 cases), the classical albuminocytological dissociation (cell count < 5/µl with elevated CSF proteins) was detected in 71.2% of the cases (42/59) with a median CSF protein of 100.0 mg/dl (min: 49, max: 317 mg/dl). Mild pleocytosis (i.e., cell count ≥ 5/µl), with a maximum cell count of 13/µl, was evident in 5/59 cases (8.5%). Furthermore, CSF SARS-CoV-2 RNA was undetectable in all tested patients (n = 31) (Table 1).
Furthermore, anti-GD1b and anti-GM1 antibodies were positive in one patient with MFS [23] and in one with clas-sic sensorimotor GBS [13], respectively, whereas 33 cases tested negative (one in equivocal range) for anti-ganglioside antibodies.
Cranial and spinal MRI scans were performed in a minor-ity of the patients (23/73, 31.5%). Five patients (three cases with AIDP [9, 12, 25], one case with MFS [30], and one case with bilateral facial palsy with paresthesia [52]) showed cranial nerve contrast enhancement in the context of cor-respondent cranial nerve palsies. Moreover, brainstem lep-tomeningeal enhancement was described in two cases with AIDP, both with clinical cranial nerve involvement [18, 46]. On the other hand, spinal nerve roots and leptomeningeal enhancement were reported in eight [9, 27, 31, 36, 37, 42, 52] and two cases [17, 46], respectively (Table 1).
Distribution of clinical and electrophysiological variants and diagnosis of GBS
From the clinical point of view, most examined patients presented with a classic sensorimotor variant (70.0%,
1136 Journal of Neurology (2021) 268:1133–1170
1 3
51/73), whereas Miller Fisher syndrome, GBS/MFS over-lap variants (including polyneuritis cranialis), bilateral facial palsy with paresthesia, pure motor, and paraparetic were described in seven, two, five, four, and one patients, respectively. In three cases, no clinical variant could be established using the reported details (Table 1). In the examined population, 81.8% subjects fulfilled electro-physiological criteria for AIDP (45/55), 12.7% (7/55) for AMSAN, and 5.4% (3/55) for AMAN subtypes. Finally, a specific electrophysiological subtype was not attributable in 18 patients due to the lack of detailed information. The diagnosis of GBS was established based on clinical, CSF, and electrophysiological findings in 44/73 (60.3%) patients, clinical, and electrophysiological data in 18/73 (24.7%) cases, clinical, and CSF data in 8/73 (11.0%), and only clinical findings in 3/73 (4.1%) patients. Indeed, the highest level of diagnostic certainty (level one) was confirmed in 44/73 cases (60.3%). Level two and three were obtained in 24/73 cases (32.9%) and 5/73 (6.8%), respectively (Table 1).
Management of GBS and patient outcomes
All cases with available therapy data (n = 70) except ten [13, 15, 23, 25, 26, 33, 35–37, 41] were treated with intrave-nous immunoglobulin (IVIG) (Table 1). Conversely, plasma exchange and steroid therapy were performed in ten (four of them received also IVIG) and two cases, respectively. In two patients, no therapy was given. Mechanical or non-invasive ventilation was implemented in 21.4% (15/70) and 7.1% (5/70) patients due to worsening of GBS or COVID-19, respectively. At further observation (n = 68), 72.1% (49/68) patients demonstrated clinical improvement with partial or complete remission, 10.3% (7/68) cases showed no improve-ment, 11.8% (8/68) still required critical care treatment, and 5.8% (4/68) died (Table 1).
Interestingly, patients with no improvement or poor outcome (n = 19) showed a slightly higher (but not signif-icant) frequency of clinical history and/or a radiological picture of COVID-19 pneumonia (14/19, 73.7%) com-pared to those with a favorable prognosis (29/48, 60.4%, p = 0.541). Moreover, the former group of patients was significantly older (mean 62.7 ± 17.8 years, p = 0.011), but with comparable distribution of sex (p = 0.622) and electrophysiological subtypes (p = 0.144) and simi-lar latency between COVID-19 and GBS (p = 0.588) and nadir (p = 0.825), compared to the latter (mean age 51.8 ± 16.6 years). The same findings were confirmed even after excluding cases with no improvement from the analysis (to prevent a possible bias related to the short follow-up time).
Discussion
COVID-19 pandemic prompts all efforts for the early rec-ognition and treatment of its manifestations. In analogy to other viruses, belonging or not to the coronavirus fam-ily [63, 67], neurologic complications in COVID-19 are emerging as one of the most significant clinical chapters of this pandemic. In this regard, peripheral and central nerv-ous system damage in COVID-19 has been postulated to be the consequence of two different mechanisms: 1) hema-togenous (infection of endothelial cells or leucocytes) or trans-neuronal (via olfactory tract or other cranial nerves) dissemination to central nervous system in relation with viral neurotropism, and 2) abnormal immune-mediated response causing secondary neurological involvement [62, 68, 69]. The first mechanism is supposed to be responsible for the most common neurological symptoms developed by patients with COVID-19 (e.g., hypogeusia, hyposmia, headache, vertigo, and dizziness). In contrast, the second can lead to severe complications during or after the course of the ill-ness, either dysimmune (e.g., myelitis, encephalitis, GBS) or induced by cytokine overproduction (hypercoagulable state and cerebrovascular events) [68, 69].
In the present systematic review, we reviewed clinical features, results of diagnostic investigations, and outcome in 73 cases of COVID-19-associated GBS spectrum [5–56].
In the present study, mean age at onset in patients with GBS largely overlapped that of classic COVID-19 sub-jects [70, 71]. However, pediatric cases with GBS have been increasingly reported in the literature [21, 27, 35, 41], sug-gesting that, with the spreading of the pandemic, a broader age range might be affected. Moreover, we found a higher prevalence of GBS in males compared to females, as previ-ously reported for Zika virus–GBS [72]. This finding may also reflect the gender epidemiology of SARS-CoV-2. In this regard, males typically show a worse COVID-19 outcome compared to the females [70, 71], possibly due to a generally shorter life expectancy or to higher circulating Angiotensin-Converting-Enzyme 2 (ACE2) levels, the cellular receptor for SARS-CoV-2, in the former compared to the latter [71]. Moreover, given that GBS is a rare disease [57] the epide-miological distribution of the reported cases seems to reflect current worldwide outbreaks, with Europe being the “hot-test” spot in March–May 2020 and USA together with Asia in the following period [73, 74]. On another issue, despite a few GBS cases seemed to have a para-infectious profile [10, 37, 38, 40, 55, 56] as described for Zika virus [75], all other reported patients developed neurological symptoms with a typical latency after COVID-19 (median time 14 days). This feature, together with the frequently reported negative naso-pharyngeal swab at GBS onset [22, 24, 36, 44, 45, 52] and clinical improvement after IVIG therapy, seems to support
1137Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
Sum
mar
y of
clin
ical
find
ings
, res
ults
of d
iagn
ostic
inve
stiga
tions
, and
out
com
e in
73
GB
S ca
ses
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Ago
sti e
t al.
[5]
Italy
68M
5 da
ys a
fter
LL w
eakn
ess
Bila
tera
l fac
ial
pals
y, p
rogr
es-
sive
sym
met
ric
asce
ndin
g fla
ccid
te
trapa
resi
s, ac
hille
s ten
don
arefl
exia
NA
No
NA
Dry
cou
gh
asso
ciat
ed
with
feve
r, dy
sgeu
sia,
an
d hy
posm
ia
Dys
-lip
idem
ia,
beni
gn
pros
tatic
hy
pertr
o-ph
y, h
yper
-te
nsio
n,
abdo
min
al
aorti
c an
eury
sm
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Pure
mot
or
Alb
erti
et a
l. [6
]Ita
ly71
M4
days
afte
r (n
o re
so-
lutio
n of
pn
eum
o-ni
a)
LL p
arae
sthe
sia
Asc
enda
nt w
eak-
ness
, flac
cid
tetra
pare
sis,
hypo
esth
esia
an
d pa
raes
-th
esia
in th
e 4
limbs
, gen
eral
-iz
ed a
refle
xia,
dy
spne
a
Non
eYe
s (co
ncur
-re
nt p
neu-
mon
ia)
4 da
ys a
fter
sym
ptom
s on
set
(24
h af
ter
the
adm
is-
sion
)
Feve
r (lo
w
grad
e),
dysp
nea,
pn
eum
onia
Hyp
erte
n-si
on,
treat
ed
abdo
min
al
aorti
c an
eury
sm,
treat
ed
lung
can
cer
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Arn
aud
et a
l. [7
]Fr
ance
64M
23 d
ays
afte
rFa
st pr
ogre
s-si
ve L
L w
eakn
ess
Gen
eral
ized
ar
eflex
ia,
seve
re fl
acci
d pr
oxim
al
para
pare
sis,
decr
ease
d pr
oprio
cept
ive
leng
th-
depe
nden
t se
nsiti
vity
and
LL
pin
pric
k an
d lig
ht to
uch
hypo
esth
esia
Non
eN
o4
days
afte
r sy
mpt
oms
onse
t
Feve
r, co
ugh,
di
arrh
ea,
dysp
nea,
se
vere
in
ters
titia
l pn
eum
onia
DM
type
2C
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Ass
ini e
t al.
[8]
Italy
55M
20 d
ays
afte
rB
ilate
ral
eyel
id p
tosi
s, dy
spha
gia,
dy
spho
nia
Mas
sete
r wea
k-ne
ss, t
ongu
e pr
otus
ion
(bila
tera
l hyp
o-gl
ossa
l ner
ve
para
lysi
s),
UL
and
LL
hypo
refle
xia
with
out m
uscl
e w
eakn
ess,
soft
pala
te e
leva
-tio
n de
fect
Non
eYe
s (co
ncur
-re
nt p
neu-
mon
ia)
NA
Feve
r, an
osm
ia,
ageu
sia,
co
ugh,
pne
u-m
onia
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
Cla
ssic
sen-
sorim
otor
ov
erla
p-pi
ng w
ith
Mill
er-
Fish
er
1138 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Ass
ini e
t al.
[8]
Italy
60M
20 d
ays
afte
rD
istal
tetra
pare
-si
s with
righ
t fo
ot d
rop,
au
tono
mic
di
sturb
ance
s
UL
and
LL d
istal
w
eakn
ess,
right
foot
dro
p,
gene
raliz
ed
arefl
exia
Gas
tropl
egia
, pa
raly
tic
ileus
, los
s of
blo
od
pres
sure
co
ntro
l
Yes (
conc
ur-
rent
pne
u-m
onia
)
NA
Feve
r, se
vere
in
ters
titia
l pn
eum
onia
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
Pure
mot
or
Big
aut e
t al.
[9]
Fran
ce43
M21
day
s af
ter
UL
and
LL
para
esth
esia
, di
stal
LL
wea
knes
s
Exte
nsio
n to
m
idth
igh
and
tips o
f the
fin
ger w
ith
atax
ia, r
ight
pe
riphe
ral
faci
al n
erve
pa
lsy,
gen
eral
-iz
ed a
refle
xia
Non
eN
o2
days
afte
r sy
mpt
oms
onse
t
Cou
gh,
asth
enia
, m
yalg
ia in
le
gs, f
ollo
wed
by
acu
te
anos
mia
and
ag
eusi
a w
ith
diar
rhea
, mild
in
ters
titia
l pn
eum
onia
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Big
aut e
t al.
[9]
Fran
ce70
F10
day
s af
ter
Acu
te p
roxi
mal
te
trapa
re-
sis,
dist
al
fore
limb
and
perio
ral
para
esth
esia
Resp
irato
ry
wea
knes
s, lo
ss
of a
mbu
latio
n
Non
eYe
s3
days
afte
r sy
mpt
oms
onse
t
Ano
smia
, age
u-si
a, d
iarr
hea,
as
then
ia,
mya
lgia
, m
oder
ate
inte
rstit
ial
pneu
mon
ia
Obe
sity
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Bra
cagl
ia e
t al.
[10]
Italy
66F
Unk
now
n (d
ue to
as
ymp-
tom
atic
in
fec-
tion)
Acu
te p
roxi
mal
an
d di
stal
te
trapa
resi
s, lu
mba
r pai
n an
d di
stal
tin
glin
g se
n-sa
tion
Loss
of a
mbu
la-
tion,
diffi
culty
in
spee
chin
g an
d sw
allo
w-
ing,
gen
eral
-iz
ed a
refle
xia
Non
eN
oN
AA
sym
ptom
atic
Non
eC
linic
al +
ele
ctro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Cam
dess
anch
e et
al.
[11]
Fran
ce64
M11
day
s af
ter
UL
and
LL
para
esth
esia
Asc
ende
nt w
eak-
ness
, flac
cid
tetra
pare
sis,
gene
raliz
ed
arefl
exia
, dy
spha
gia
Non
eYe
s3
days
afte
r sy
mpt
oms
onse
t
Feve
r (hi
gh
grad
e),
coug
h, p
neu-
mon
ia
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Cha
n et
al.
[12]
Can
ada
58M
20 d
ays
afte
r ho
me
isol
a-tio
n fo
r su
spec
ted
cont
act
Bila
tera
l fac
ial
wea
knes
s, dy
sarth
ria,
feet
par
aes-
thes
ia, L
L ar
eflex
ia
NA
Non
eN
oN
AA
sym
ptom
atic
, in
ters
titia
l pn
eum
onia
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1B
ilate
ral
faci
al
pals
yw
ith p
arae
s-th
esia
1139Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Cha
n et
al.
[13]
USA
68M
18 d
ays
afte
rG
ait d
istur
-ba
nce,
han
ds
and
feet
pa
raes
thes
ia
LL p
roxi
mal
w
eakn
ess,
abse
nt v
ibra
-to
ry a
nd
prop
rioce
p-tiv
e se
nse
at
the
toes
, UL
hypo
refle
xia,
LL
are
flexi
a,
unste
ady
gait
with
inab
ility
to
toe
or h
eel
wal
k, b
ilate
ral
faci
al w
eak-
ness
, dys
pha-
gia,
dys
arth
ria,
neck
flex
ion
wea
knes
s
Non
eN
o8
days
afte
r th
e on
set
of sy
mp-
tom
s
Feve
r and
upp
er
resp
irato
ry
sym
ptom
s
NA
Clin
ical
+ C
SF2
Cla
ssic
se
nsor
i-m
otor
Cha
n et
al.
[13]
USA
84M
16 d
ays
afte
rH
ands
and
feet
pa
raes
thes
ia,
prog
ress
ive
gait
distu
r-ba
nce
Bila
tera
l fac
ial
wea
knes
s, pr
ogre
ssiv
e ar
m w
eakn
ess,
neur
omus
cula
r re
spira
tory
fa
ilure
Yes (
not
spec
ified
au
tono
mic
dy
sfun
c-tio
n)
Yes
25 d
ays a
fter
the
onse
t of
sym
p-to
ms
Feve
rN
AC
linic
al +
CSF
2C
lass
ic
sens
ori-
mot
or
Coe
n et
al.
[14]
Switz
er-
land
70M
6 da
ys a
fter
Para
pare
sis,
dist
al a
llo-
dyni
a
Gen
eral
ized
ar
eflex
iaD
ifficu
lties
in
voi
ding
an
d co
nsti-
patio
n
No
NA
Dry
cou
gh,
mya
lgia
, fa
tigue
Non
eC
linic
al +
CSF
+
0ele
ctro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Ebra
him
zade
h et
al.
[15]
Iran
46M
18 d
ays
afte
rPa
in a
nd n
umb-
ness
in d
istal
LL
and
UL
extre
miti
es,
asce
ndin
g w
eakn
ess i
n le
gs
Mild
per
iphe
ral
right
faci
al
nerv
e pa
lsy,
ge
nera
lized
ar
eflex
ia
Non
eN
o7
days
afte
r sy
mpt
oms
onse
t
Low
-gra
de
feve
r, so
re
thor
at, d
ry
coug
h an
d m
ild d
yspn
ea,
bila
tera
l in
ters
titia
l pn
eum
onia
(c
oncu
r-re
nt w
ith
neur
olog
ical
sy
mpt
oms)
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
1140 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Ebra
him
zade
h et
al.
[15]
Iran
65M
10 d
ays
afte
rPr
ogre
ssiv
e as
cend
ing
LL a
nd U
L ex
trem
ities
w
eakn
ess a
nd
para
esth
esia
Prox
imal
and
di
stal
UL
and
LL w
eakn
ess,
UL
hypo
re-
flexi
a an
d LL
ar
eflex
ia
Non
eN
o14
day
s afte
r sy
mpt
oms
onse
t
Hist
ory
of
COV
ID-1
9 (s
ympt
oms
not s
peci
-fie
d), fi
ne
crac
kles
in
both
lung
s (c
oncu
r-re
nt w
ith
neur
olog
ical
sy
mpt
oms)
Hyp
erte
nsio
nC
linic
al +
ele
ctro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
El O
tman
i et a
l. [1
6]M
oroc
co70
F3
days
afte
rW
eakn
ess a
nd
para
esth
esia
in
the
4 lim
bs
Tetra
pare
sis,
hypo
toni
a,
gene
raliz
ed
arefl
exia
, bila
t-er
al p
ositi
ve
Lasè
gue
sign
Non
eN
oN
AD
ry c
ough
, pn
eum
onia
Rhe
umat
oid
arth
ritis
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Este
ban
Mol
ina
et a
l. [1
7]Sp
ain
55F
14 d
ays
afte
rPa
raes
thes
ia
and
wea
knes
s in
the
4 lim
bs
Lum
bar p
ain,
dy
spha
gia,
te
trapl
egia
, ge
nera
l ar
eflex
ia,
bila
tera
l fac
ial
pals
y, li
ngua
l an
d pe
riora
l pa
raes
thes
ia
Non
eYe
s3
days
afte
r sy
mpt
oms
onse
t (4
8 h
afte
r th
e ad
mis
-si
on)
Feve
r, dr
y co
ugh
and
dysp
noea
, pn
eum
onia
Dys
lipid
emia
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Farz
i et a
l. [1
8]Ir
an41
M10
day
s af
ter
Para
esth
esia
of
the
feet
Tetra
pare
sis,
arefl
exia
at
the
LL a
nd
hypo
refle
xia
at th
e U
L,
stock
ing-
and-
glov
e hy
pes-
thes
ia a
nd
redu
ced
sens
e of
vib
ratio
n an
d po
sitio
n
Non
eN
o7
days
afte
r sy
mpt
oms
onse
t
Cou
gh, d
yspn
ea
and
feve
rD
M ty
pe II
Clin
ical
+ el
ectro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Fern
ánde
z–D
omín
guez
et
al.
[19]
Spai
n74
F15
day
s af
ter
Gai
t ata
xia
and
gene
raliz
ed
arefl
exia
NA
NA
No
NA
Resp
irato
ry
sym
ptom
s (n
ot fu
rther
de
taile
d)
Hyp
erte
n-si
on a
nd
folli
cula
r ly
mph
oma
Clin
ical
+ C
SF2
Mill
er
Fish
er
varia
nt
Fins
tere
r et a
l. [2
0]In
dia
20M
5 da
ys a
fter
NA
NA
NA
NA
NA
NA
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
NA
1141Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Fran
k et
al.
[21]
Bra
zil
15M
> 5
day
s af
ter
Para
pare
sis,
pain
in th
e LL
Rap
idly
pro
gres
-si
ve a
scen
ding
te
trapa
resi
s, ar
eflex
ia
NA
No
NA
Feve
r, in
tens
e sw
eatin
gN
AC
linic
al +
elec
tro-
phys
iolo
gy2
Cla
ssic
se
nsor
i-m
otor
Gig
li et
al.
[22]
Italy
53M
NA
Para
esth
esia
, ga
it at
axia
NA
NA
NA
NA
Feve
r, di
arrh
eaN
AC
linic
al +
CSF
+ el
ec-
troph
ysio
logy
1N
A
Gut
iérr
ez-O
rtiz
et a
l. [2
3]Sp
ain
50M
3 da
ys a
fter
Verti
cal d
iplo
-pi
a, p
erio
ral
para
esth
esia
, ga
it at
axia
Rig
ht in
tern
u-cl
ear o
phth
al-
mop
ares
is a
nd
right
fasc
icul
ar
ocul
omot
or
pals
y, a
taxi
a,
gene
raliz
ed
arefl
exia
Non
eN
oN
AFe
ver,
coug
h,
mal
aise
, he
adac
he,
low
bac
k pa
in, a
nos-
mia
, age
usia
Bro
nchi
al
asth
ma
Clin
ical
+ C
SF2
Mill
er
Fish
er
varia
nt
Gut
iérr
ez-O
rtiz
et a
l. [2
3]Sp
ain
39M
3 da
ys a
fter
Dip
lopi
a (b
ilat-
eral
abd
ucen
s pa
lsy)
Gen
eral
ized
ar
eflex
iaN
one
No
NA
Dia
rrhe
a, lo
w-
grad
e fe
ver
Non
eC
linic
al +
CSF
2Po
lyne
uriti
s cr
ania
lis
(GB
S–M
iller
Fi
sher
In
terfa
ce)
Hel
bok
et a
l. [2
4]A
ustri
a68
M14
day
s af
ter
Hyp
oaes
thes
ia
and
para
es-
thes
ia in
the
LL, p
roxi
mal
w
eakn
ess,
arefl
exia
, st
and
atax
ia
Asc
endi
ng w
eak-
ness
, flac
cid
tetra
pare
sis,
gene
raliz
ed
arefl
exia
NA
Yes
2 da
ys a
fter
sym
ptom
s on
set
(24
h af
ter
the
adm
is-
sion
)
Feve
r, dr
y co
ugh,
mya
l-gi
a, a
nosm
ia
and
ageu
sia.
Non
eC
linic
al +
CSF
+ el
ec-
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Hut
chin
s et a
l. [2
5]U
SA21
M16
day
s af
ter
Rig
ht-s
ided
fa
cial
num
b-ne
ss a
nd
wea
knes
s
Bila
tera
l fac
ial
pals
y, se
vere
dy
sarth
ria,
bila
tera
l LL
wea
knes
s , b
ilate
ral U
L pa
raes
thes
ia,
arefl
exia
NA
No
3 da
ys a
fter
sym
ptom
s on
set
Feve
r, co
ugh,
dy
spno
ea,
diar
rhea
, na
usea
, he
adac
he
Hyp
erte
n-si
on, p
re-
diab
etes
, an
d cl
ass I
ob
esity
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Bila
tera
l fa
cial
pa
lsy
with
pa
raes
-th
esia
Julia
o C
aam
año
et a
l. [2
6]Sp
ain
61M
10 d
ays
afte
rFa
cial
dip
legi
aN
o pr
ogre
ssio
nN
one
No
1 da
y af
ter
sym
ptom
s on
set
Feve
r and
co
ugh
Non
eC
linic
al +
elec
tro-
phys
iolo
gy3
Bila
tera
l fa
cial
ne
rve
pals
y
1142 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Kha
lifa
et a
l. [2
7]K
ingd
om
of S
audi
A
rabi
a
11M
20 d
ays
afte
rG
ait a
taxi
a,
arefl
exia
and
pa
raes
thes
ia
in th
e LL
Gra
dual
mot
or
impr
ovem
ent,
pers
isten
t hy
pore
flexi
a
NA
No
NA
Acu
te u
pper
re
spira
tory
tra
ct in
fec-
tion,
low
-gr
ade
feve
r, dr
y co
ugh.
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Kili
nc e
t al.
[28]
The
Net
h-er
land
s50
M24
day
s af
ter
Faci
al d
iple
gia,
sy
mm
etric
al
prox
imal
w
eakn
ess,
para
esth
esia
of
dist
al
extre
miti
es,
gait
atax
ia,
arefl
exia
Prog
ress
ion
of
limb
wea
knes
s an
d in
abili
ty to
w
alk
NA
No
11 d
ays a
fter
sym
ptom
s on
set
Dry
cou
ghN
one
Clin
ical
+ el
ectro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Lam
pe e
t al.
[29]
Ger
man
y65
M2
days
afte
rA
cute
righ
t UL
and
LL w
eak-
ness
cau
sing
re
curr
ent f
alls
Rig
ht U
L pa
re-
sis,
slig
ht p
ara-
pare
sis m
ore
pron
ounc
ed o
n th
e rig
ht si
de,
gene
raliz
ed
hypo
refle
xia
Non
eN
o3
days
afte
r sy
mpt
oms
onse
t
Feve
r and
dry
co
ugh
Non
eC
linic
al +
CSF
+ el
ec-
troph
ysio
logy
1Pu
re m
otor
Lant
os e
t al.
[30]
USA
36M
4 da
ys a
fter
Opt
halm
opa-
resi
sa a
nd
hypo
esth
esia
be
low
kne
e
Prog
ress
ive
oph-
thal
mop
ares
is
(incl
udin
g in
itial
left
III c
rani
al
nerv
e an
d ev
entu
al b
ilat-
eral
VI c
rani
al
nerv
e pa
lsie
s),
atax
ia, a
nd
hypo
refle
xia
Non
eN
oN
AFe
ver,
chill
s, an
d m
yalg
iaN
one
Clin
ical
3M
iller
Fi
sher
va
riant
Lasc
ano
et a
l. [3
1]Sw
itzer
-la
nd52
F15
day
s af
ter (
no
reso
lu-
tion
of
pneu
mo-
nia)
Bac
k pa
in, d
iar-
rhea
, rap
idly
pr
ogre
ssiv
e te
trapa
resi
s, di
stal
par
aes-
thes
ia
Wor
seni
ng o
f pr
oxim
al
wea
knes
s (te
trapl
egia
), ge
nera
lized
ar
eflex
ia,
atax
ia
Con
stipa
tion,
ab
dom
inal
pa
in
Yes
4 da
ys a
fter
sym
ptom
s on
set
Dry
cou
gh,
dysg
eusi
a,
caco
smia
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
1143Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Lasc
ano
et a
l. [3
1]Sw
itzer
-la
nd63
F7
days
afte
r (n
o re
so-
lutio
n of
pn
eum
o-ni
a)
Lim
b w
eak-
ness
, pai
n on
th
e le
ft ca
lf
Mod
erat
e te
trapa
resi
s, LL
and
left
UL
arefl
exia
, dist
al
hypo
esth
esia
an
d pa
raes
-th
esia
Non
eN
o5
days
afte
r sy
mpt
oms
onse
t
Dry
cou
gh,
shiv
erin
g,
brea
thin
g di
fficu
lties
, ch
est p
ain,
od
ynop
hagi
a
DM
type
2C
linic
al +
ele
ctro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Lasc
ano
et a
l. [3
1]Sw
itzer
-la
nd61
F22
day
s af
ter
LL w
eakn
ess,
dizz
ines
s, dy
spha
gia
Mod
erat
e te
trapa
resi
s, bi
late
ral f
acia
l pa
lsy,
low
er
limb
allo
dyni
a,
seve
re h
ypo-
palle
sthe
sia,
ar
eflex
ia
(exc
ept f
or
bici
pita
l ten
-do
n re
flexe
s)
Non
eYe
s4
days
afte
r sy
mpt
oms
onse
t
Prod
uctiv
e co
ugh,
hea
d-ac
hes,
feve
r, m
yalg
ia, d
iar-
rhea
, nau
sea,
vo
miti
ng,
wei
ght l
oss,
recu
rren
t ep
isod
es o
f tra
nsie
nt lo
ss
of c
onsc
ious
-ne
ss
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Man
gano
tti e
t al.
[32]
Italy
50F
16 d
ays
afte
rD
iplo
pia
and
faci
al p
arae
s-th
esia
Ata
xia,
dip
lopi
a in
ver
tical
and
la
tera
l gaz
e,
left
uppe
r arm
dy
smet
ria,
gene
raliz
ed
arefl
exia
, mild
lo
wer
faci
al
defe
cts,
and
mild
hyp
oes-
thes
ia in
the
left
man
dibu
lar
and
max
illar
y br
anch
Non
eYe
s (co
ncur
-re
nt p
neu-
mon
ia)
NA
Feve
r, co
ugh,
ag
eusi
a,
bila
tera
l pn
eum
onia
Non
eC
linic
al +
CSF
2M
iller
Fi
sher
va
riant
Man
gano
tti e
t al.
[33]
Italy
72M
18 d
ays
afte
rTe
trapa
resi
s U
L >
LL,
LL
para
esth
esia
, g
ener
aliz
ed
arefl
exia
, fa
cial
wea
k-ne
ss o
n th
e rig
ht si
de
NA
NA
No
NA
Feve
r, dy
spne
a,
hypo
smia
and
ag
eusi
a
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
1144 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Man
gano
tti e
t al.
[33]
Italy
72M
30 d
ays
afte
rTe
trapa
resi
s LL
> U
L,
para
esth
e-si
a, g
loba
l ar
eflex
ia
NA
NA
No
NA
Feve
r, co
ugh,
dy
spne
a,
hypo
smia
and
ag
eusi
a
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Man
gano
tti e
t al.
[33]
Italy
49F
14 d
ays
afte
rO
phth
al-
mop
legi
a,
limb
atax
ia,
gene
raliz
ed
arefl
exia
, di
plop
ia,
faci
al h
ypoe
s-th
esia
, fac
ial
wea
knes
s
NA
NA
No
NA
Feve
r, co
ugh,
dy
spne
a,
hypo
smia
and
ag
eusi
a
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Mill
er
Fish
er
varia
nt
Man
gano
tti e
t al.
[33]
Italy
94M
33 d
ays
afte
rLL
wea
knes
s, ge
nera
lized
hy
pore
flexi
a
NA
NA
No
NA
Feve
r, co
ugh,
ga
stroi
ntes
ti-na
l sym
ptom
s
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
Cla
ssic
se
nsor
i-m
otor
Man
gano
tti e
t al.
[33]
Italy
76M
22 d
ays
afte
rQ
uadr
ipar
esis
U
L >
LL,
ge
nera
lized
ar
eflex
ia,
faci
al
wea
knes
s, tra
nsie
nt
dipl
opia
NA
NA
No
NA
Feve
r, co
ugh,
dy
suria
, hy
posm
ia,
ageu
sia
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Pure
mot
or
Mar
ta-E
ngui
ta
et a
l. [3
4]Sp
ain
76F
8 da
ys a
fter
Bac
k pa
in a
nd
prog
ress
ive
tetra
pare
-si
s with
di
stal
-ons
et
para
esth
esia
Prog
ress
ive
with
dy
spha
gia
and
cran
ial n
erve
s in
volv
emen
t, ge
nera
lized
ar
eflex
ia
NA
Yes
10 d
ays a
fter
sym
ptom
on
set
Cou
gh a
nd
feve
r with
out
dysp
nea
Non
eC
linic
al3
NA
Moz
hdeh
ipan
ah
et a
l. [3
5]Ir
an38
M16
day
s af
ter
Prog
ress
ive
LL p
arae
s-th
esia
, fac
ial
dipl
egia
, lo
bal a
re-
flexi
a
Mild
LL
wea
k-ne
ss ,
bulb
ar
sym
ptom
s de
velo
ped
Blo
od
pres
sure
in
stab
ility
, ta
chyc
ar-
dia
No
8 da
ys a
fter
sym
ptom
s on
set
Upp
er re
spira
-to
ry in
fect
ion
(no
furth
er
deta
ils)
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Bila
tera
l fa
cial
pa
lsy
with
pa
raes
-th
esia
Moz
hdeh
ipan
ah
et a
l. [3
5]Ir
an14
FN
AA
scen
ding
qu
adrip
a-re
sis,
UL
hypo
refle
xia,
LL
are
flexi
a,
dist
al h
ypoe
s-th
esia
, ata
xia
NA
NA
No
NA
Upp
er re
spira
-to
ry in
fect
ion
(no
furth
er
deta
ils)
NA
Clin
ical
+ C
SF2
Cla
ssic
se
nsor
i-m
otor
1145Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Moz
hdeh
ipan
ah
et a
l. [3
5]Ir
an44
F26
day
s af
ter
Wea
knes
s of
LLTe
trapa
resi
s, ge
nera
lized
ar
eflex
ia,
sym
met
rical
hy
poes
thes
ia
NA
Yes
NA
Dry
cou
gh,
feve
r, m
yalg
ia,
prog
ress
ive
dysp
nea
COPD
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Moz
hdeh
ipan
ah
et a
l. [3
5]Ir
an66
F30
day
s af
ter
Prog
ress
ive
UL
and
LL w
eakn
ess,
gene
raliz
ed
arefl
exia
, sy
mm
etric
al
hypo
esth
esia
NA
No
No
NA
Feve
r, dr
y co
ugh,
seve
re
mya
lgia
DM
, hy
perte
n-si
on, a
nd
rheu
mat
oid
arth
ritis
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Nad
daf e
t al.
[36]
USA
58F
17 d
ays
afte
rPr
ogre
ssiv
e pa
rapa
resi
s, im
bala
nce,
se
vere
low
er
thor
acic
pa
in w
ithou
t ra
diat
ion
Mild
nec
k fle
x-io
n w
eakn
ess,
mild
/mod
er-
ate
dist
al U
L
and
prox
imal
an
d di
stal
LL
w
eakn
ess,
UL
hypo
refle
xia,
LL
are
flexi
a,
mod
erat
ely
seve
re le
ngth
-de
pend
ent
sens
ory
loss
in
the
feet
, ata
xic
gait
Non
eN
oN
AFe
ver,
dysg
eu-
sia
with
out
anos
mia
, bi
late
ral
inte
rstit
ial
pneu
mon
ia
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Ogu
z-A
kars
u et
al.
[37]
Turk
ey53
FC
oncu
rren
t pn
eum
o-ni
a
Dys
arth
ria,
prog
ress
ive
LL w
eakn
ess
and
num
b-ne
ss
Ata
xia,
gen
eral
-iz
ed a
refle
xia
Non
eN
oN
AM
ild fe
ver
(37.
5 °C
), pn
eum
onia
Non
eC
linic
al +
ele
ctro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Otta
vian
i et a
l. [3
8]Ita
ly66
F7
days
afte
r (c
oncu
r-re
nt
pneu
mo-
nia)
Flac
cid
para
pare
sis,
no se
nsor
y sy
mpt
oms
Prog
ress
ivel
y de
velo
ped
prox
imal
w
eakn
ess
in a
ll lim
bs,
dyse
sthe
sia,
an
d un
ilate
ral
faci
al p
alsy
, ge
nera
lized
ar
eflex
ia
NA
Yes
13 d
ays a
fter
sym
ptom
s on
set
Feve
r and
co
ugh,
pne
u-m
onia
NA
Clin
ical
+ C
SF +
elec
-tro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
1146 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Padr
oni e
t al.
[39]
Italy
70F
23 d
ays
afte
rU
L an
d LL
pa
raes
thes
ia,
gait
diffi
cul-
ties,
asth
enia
Asc
enda
nt w
eak-
ness
, tet
rapa
re-
sis,
gene
raliz
ed
arefl
exia
Non
eYe
s6
days
afte
r sy
mpt
oms
onse
t
Feve
r (38
.5 °C
), dr
y co
ugh,
pn
eum
onia
Non
eC
linic
al +
CSF
+ E
lec-
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Pate
rson
et a
l. [4
0]U
K42
M13
day
afte
rD
istal
lim
b nu
mb-
ness
and
w
eakn
ess,
dysp
hagi
a
Tetra
pare
sis,
gene
raliz
ed
arefl
exia
, se
nsor
y lo
ss
NA
Yes
16 d
ays a
fter
sym
ptom
on
set
Cou
gh, f
ever
dy
spne
a,
diar
rhea
, an
osm
ia
Non
eC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Pate
rson
et a
l. [4
0]U
K60
M1
day
befo
reD
istal
lim
b nu
mbn
ess
and
wea
knes
s
Tetra
pare
sis,
gene
raliz
ed
arefl
exia
, se
nsor
y lo
ss,
dysa
uton
omia
, fa
cial
and
bul
-ba
r wea
knes
s
Yes
Yes
5 da
ys a
fter
sym
ptom
on
set
Hea
dach
e,
ageu
sia,
an
osm
ia
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Pate
rson
et a
l. [4
0]U
K38
M21
day
afte
rD
istal
lim
b nu
mbn
ess,
wea
knes
s, cl
umsi
ness
Mild
dist
al w
eak-
ness
, sen
sory
at
axia
Non
eN
oN
AC
ough
, dia
rrhe
aN
AC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Payb
ast e
t al.
[41]
Iran
38M
21 d
ays
afte
rA
cute
pr
ogre
ssiv
e as
cend
ing
para
esth
esia
of
dist
al L
L
Qua
drip
ares
the-
sia,
bila
tera
l fa
cial
dro
op
with
dro
olin
g of
saliv
a an
d sl
urre
d sp
eech
, ge
nera
lized
ar
eflex
ia,
swal
low
ing
inab
ility
, bila
t-er
ally
abs
ent
gag
refle
x
Tach
ycar
dia
and
bloo
d pr
essu
re
inst
abili
ty
No
3 da
ys a
fter
sym
ptom
s on
set
Sym
ptom
s of
uppe
r res
-pi
rato
ry tr
act
infe
ctio
n
Hyp
erte
nsio
nC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
1147Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Payb
ast e
t al.
[41]
Iran
14F
21 d
ays
afte
rPr
ogre
ssiv
e as
cend
ing
quad
ripar
es-
thes
ia, m
ild
LL w
eakn
ess
Mild
pro
xim
al
and
dist
al L
L w
eakn
ess,
hypo
activ
e de
ep te
ndon
re
flexe
s in
UL
and
abse
nt in
LL
, dec
reas
ed
light
touc
h,
posi
tion,
and
vi
brat
ion
sens
atio
n in
all
dist
al li
mbs
up
to a
nkle
and
el
bow
join
ts,
gait
atax
ia
Non
eN
o2
days
afte
r sy
mpt
oms
onse
t
Sym
ptom
s of
uppe
r res
-pi
rato
ry tr
act
infe
ctio
n
Non
eC
linic
al +
CSF
2C
lass
ic
sens
ori-
mot
or
Pfeff
erko
rn e
t al.
[42]
Ger
man
y51
M14
day
s af
ter
UL
and
LL
wea
knes
s, ac
ral p
arae
s-th
esia
Tetra
pare
sis,
gene
raliz
ed
arefl
exia
, de
terio
ratio
n to
an
alm
ost
com
plet
e pe
riphe
ral
lock
ed-in
sy
ndro
me
with
te
trapl
egia
, co
mpl
ete
sen-
sory
loss
at 4
lim
bs, b
ilate
ral
faci
al a
nd
hypo
glos
sal
pare
sis
Non
eYe
s15
day
s afte
r sy
mpt
oms
onse
t
Fluc
tuat
ing
feve
r, flu
-like
sy
mpt
oms
with
mar
ked
fatig
ue a
nd
dry
coug
h,
pneu
mon
ia
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Ran
a et
al.
[43]
USA
54M
14 d
ays
afte
rLL
par
esth
esia
s of
LL
Asc
endi
ng
tetra
pare
sis,
gene
ral a
re-
flexi
a, b
urni
ng
sens
atio
n di
plop
ia, f
acia
l di
pleg
ia, m
ild
opht
halm
opa-
resi
s
Resti
ng
tach
ycar
-di
a an
d ur
inar
y re
tent
ion
Yes
NA
Rhi
norr
hea,
od
ynop
hagi
a,
feve
r, ch
ills,
and
nigh
t sw
eats
Hyp
erte
n-si
on,
hype
r-lip
idem
ia,
restl
ess l
eg
synd
rom
e,
and
chro
nic
back
pai
n,
conc
urre
nt
C. D
iffici
le
infe
ctio
n
Clin
ical
+ el
ectro
-ph
ysio
logy
2M
iller
Fi
sher
va
riant
1148 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Reye
s-B
ueno
et
al.
[44]
Spai
n50
F15
day
s af
ter
Root
-type
pai
n in
all
four
lim
bs, d
orsa
l an
d lu
mba
r ba
ck p
ain
LL W
eakn
ess,
atax
ia, d
iplo
-pi
a, b
ilate
ral
faci
al p
alsy
, ge
nera
lized
ar
eflex
ia
Dry
mou
th,
diar
rhea
an
d un
sta-
ble
bloo
d pr
essu
re
No
12 d
ays a
fter
sym
ptom
s on
set
Dia
rrhe
a,
odyn
opha
gia
and
coug
h
NA
Clin
ical
+ C
SF +
elec
-tro
phys
iolo
gy1
Mill
er
Fish
er
varia
nt
Riv
a et
al.
[45]
Italy
60+
M17
day
s af
ter
Prog
res-
sive
lim
b w
eakn
ess
and
dist
al
pare
sthe
sia
at
four
lim
bs
Asc
endi
ng p
ara-
pare
sis w
ith
invo
lvem
ent
of th
e cr
ania
l ne
rves
(fac
ial
dipl
egia
), ge
nera
lized
ar
eflex
ia
Non
eN
o10
day
s afte
r sy
mpt
oms
onse
t
Feve
r, he
ad-
ache
, mya
l-gi
a, a
nosm
ia
and
ageu
sia
NA
Clin
ical
+ el
ectro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
Sanc
ho-S
alda
ña
et a
l. [4
6]Sp
ain
56F
15 d
ays
afte
rU
nste
adin
ess
and
para
es-
thes
ia in
bot
h ha
nds
Lum
bar p
ain
and
asce
ndin
g w
eakn
ess,
glob
al
arefl
exia
, bi
late
ral f
acia
l ne
rve
pals
y,
orop
hary
ngea
l w
eakn
ess
and
seve
re
prox
imal
te
trapa
resi
s
No
Yes
3 da
ys a
fter
sym
ptom
s on
set
Feve
r, dr
y co
ugh
and
dysp
nea,
pn
eum
onia
NA
Clin
ical
+ C
SF +
elec
-tro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Sche
idl e
t al.
[47]
Ger
man
y54
F11
day
s af
ter
Prox
imal
wea
k-ne
ss o
f LL,
nu
mbn
ess o
f 4
limbs
Initi
al w
orse
ning
of
the
para
pa-
resi
s with
rapi
d im
prov
emen
t up
on in
itiat
ion
of th
e tre
at-
men
t, ar
eflex
ia
Non
eN
o12
day
s afte
r sy
mpt
oms
onse
t
Tem
pora
ry
ageu
sia,
Non
eC
linic
al +
CSF
+ el
ec-
troph
ysio
logy
1Pa
rapa
retic
va
riant
Seda
ghat
et a
l. [4
8]Ir
an65
M14
day
s af
ter
LL d
istal
wea
k-ne
ssA
scen
ding
w
eakn
ess,
tetra
pare
sis,
faci
al b
ilate
ral
pals
y, g
ener
al-
ized
are
flexi
a,
LL d
istal
hy
poes
thes
ia
and
hypo
pall-
esth
esia
Non
eN
o4
days
afte
r sy
mpt
oms
onse
t
Feve
r, co
ugh
and
som
etim
es
dysp
nea,
pn
eum
onia
DM
type
2C
linic
al +
ele
ctro
-ph
ysio
logy
2C
lass
ic
sens
ori-
mot
or
1149Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Sidi
g et
al.
[49]
Suda
n65
M5
days
afte
rN
umbn
ess a
nd
wea
knes
s in
both
UL
and
LL
Asc
endi
ng
wea
knes
s, bi
late
ral f
acia
l pa
raes
thes
ia
and
pals
y,
clum
sine
ss o
f U
L, te
trapa
-re
sis,
slig
ht
pala
tal m
uscl
e w
eakn
ess,
arefl
exia
Urin
ary
inco
nti-
nenc
e
Yes
NA
Low
-gra
de
feve
r, so
re
thro
at, d
ry
coug
h,
head
ache
and
ge
nera
lized
fa
tigab
ility
DM
and
H
yper
ten-
sion
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
Cla
ssic
se
nsor
i-m
otor
Su e
t al.
[50]
USA
72M
6 da
ys a
fter
Prox
imal
UL
and
LL w
eak-
ness
Prog
ress
ion
with
w
orse
ning
of
the
pare
sis,
arefl
exia
, hy
poes
thes
ia
Hyp
oten
sion
al
tern
at-
ing
with
hy
perte
n-si
on a
nd
tach
ycar
-di
a
Yes
8 da
ys a
fter
sym
ptom
s on
set
Mild
dia
rrhe
a,
anor
exia
an
d ch
ills
with
out f
ever
or
resp
irato
ry
sym
ptom
s
Cor
onar
y ar
tery
di
seas
e,
hype
rten-
sion
and
al
coho
l ab
use
Clin
ical
+ C
SF +
elec
-tro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Tiet
et a
l. [5
1]U
nite
d K
ingd
om49
M21
day
s af
ter
Dist
al L
L pa
r-ae
sthe
sia
LL a
nd U
L w
eakn
ess,
faci
al d
iple
gia,
di
stal
redu
ced
sens
atio
n to
pi
npric
k an
d vi
brat
ion
sens
e, L
L dy
sest
hesi
a,
gene
raliz
ed
arefl
exia
Non
eN
o4
days
afte
r sy
mpt
oms
onse
t
Shor
tnes
s of
bre
ath,
he
adac
he a
nd
coug
h
Sinu
sitis
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Tosc
ano
et a
l. [5
2]Ita
ly77
F7
days
afte
rU
L an
d LL
pa
raes
thes
iaFl
acci
d te
trapl
egia
, ar
eflex
ia, f
acia
l w
eakn
ess,
dys-
phag
ie, t
ongu
e w
eakn
ess
Non
eYe
sN
AFe
ver,
coug
h,
ageu
sia,
pn
eum
onia
Prev
ious
is
chem
ic
strok
e,
dive
rticu
lo-
sis,
arte
rial
hype
rten-
sion
, atri
al
fibril
latio
n
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Tosc
ano
et a
l. [5
2]Ita
ly23
M10
day
s af
ter
Faci
al d
iple
gia
LL p
arae
sthe
sia,
ge
nera
lized
ar
eflex
ia, s
en-
sory
ata
xia
Non
eN
o2
days
afte
r sy
mpt
oms
onse
t
Feve
r, ph
aryn
-gi
tisN
AC
linic
al +
CSF
+
elec
troph
ysio
logy
1B
ilate
ral
faci
al
pals
y w
ith
para
es-
thes
ia
1150 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
Cou
ntry
Age
Sex
GB
S cl
inic
al p
ictu
reCO
VID
-19
clin
ical
pic
ture
Prev
ious
co
mor
bidi
ties
GB
S di
agno
sis
Leve
l of
diag
nosti
c ce
rtain
tyb
GB
S va
riant
Day
s be
twee
n CO
VID
-19
sym
ptom
s an
d G
BS
onse
t
Ons
etD
isea
se c
ours
eA
uton
omic
di
sturb
ance
sRe
spira
tory
sy
mpt
oms/
failu
re
Tim
e to
N
adira
Tosc
ano
et a
l. [5
2]Ita
ly55
M10
day
s af
ter
Nec
k pa
in, P
ar-
esth
esia
s in
the
4 lim
bs,
LL w
eakn
ess
Flac
cid
tetra
pa-
resi
s, ar
eflex
ia,
faci
al w
eak-
ness
Non
eYe
sN
AFe
ver,
coug
h,
pneu
mon
iaN
AC
linic
al +
CSF
+
elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Tosc
ano
et a
l. [5
2]Ita
ly76
M5
days
afte
rLu
mba
r pai
n,
LL w
eakn
ess
Flac
cid
tetra
pare
-si
s, ge
nera
lized
ar
eflex
ia,
atax
ia
Non
eN
o4
days
afte
r sy
mpt
oms
onse
t
Cou
gh a
nd
hypo
smia
NA
Clin
ical
+ C
SF+
Elec
troph
ysio
logy
1C
lass
ic
sens
ori-
mot
or
Tosc
ano
et a
l. [5
2]Ita
ly61
M7
days
afte
rLL
wea
knes
s an
d pa
raes
-th
esia
Asc
endi
ng
wea
knes
s, te
trapl
egia
, fa
cial
wea
k-ne
ss, a
refle
xia,
dy
spha
gia
Non
eYe
sN
AC
ough
, age
usia
an
d an
osm
ia,
pneu
mon
ia
NA
Clin
ical
+ C
SF+
ele
c-tro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Vela
yos G
alán
et
al.
[53]
Spai
n43
M10
day
s af
ter
Dist
al w
eak-
ness
and
nu
mbn
ess o
f th
e 4
limbs
, ga
it at
axia
Prog
ress
ion
of
the
wea
knes
s w
ith b
ilate
ral
faci
al p
ares
is
and
dysp
hagi
a,
gene
raliz
ed
arefl
exia
NA
No
2 da
ys a
fter
adm
issi
onC
ough
, pne
u-m
onia
NA
Clin
ical
+ e
lect
ro-
phys
iolo
gy2
Cla
ssic
se
nsor
i-m
otor
Vira
ni e
t al.
[54]
USA
54M
8 da
ys a
fter
LL w
eakn
ess,
num
bnes
sA
scen
ding
w
eakn
ess,
tetra
pare
sis,
arefl
exia
Urin
ary
rete
ntio
nYe
sSh
ortly
afte
r pr
esen
ta-
tion
in th
e ou
tpat
ient
cl
inic
(a
fter
2 da
ys o
f sy
mpt
oms
onse
t)
Feve
r (10
2 F)
, dr
y co
ugh,
pn
eum
onia
Clo
stri
dium
di
ffici
le
colit
is
2 da
ys
befo
re G
BS
onse
t
Clin
ical
3C
lass
ic
sens
ori-
mot
or
Web
b et
al.
[55]
Uni
ted
Kin
gdom
576
days
afte
rA
taxi
a, p
ro-
gres
sive
lim
b w
eakn
ess a
nd
foot
dys
aes-
thes
ia,
Tetra
pare
sis,
gene
raliz
ed
arefl
exia
, hy
poes
thes
ia
in th
e 4
limbs
, hy
popa
lles-
thes
ia in
LL,
dy
spha
gia
Non
eYe
s3
days
afte
r sy
mpt
oms
onse
t
Mild
cou
gh a
nd
head
ache
, m
yalg
ia a
nd
mal
aise
, sl
ight
feve
r, di
arrh
ea,
pneu
mon
ia
Unt
reat
ed
hype
rten-
sion
and
ps
oria
sis
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
Zhao
et a
l. [5
6]C
hina
61F
8 da
ys
befo
reLL
wea
knes
sA
scen
ding
w
eakn
ess,
tetra
pare
sis,
arefl
exia
, LL
dist
al h
ypoe
s-th
esia
Non
eN
o4
days
afte
r sy
mpt
oms
onse
t
Feve
r (38
·2 °C
), dr
y co
ugh
pneu
mon
ia
NA
Clin
ical
+ C
SF +
el
ectro
phys
iolo
gy1
Cla
ssic
se
nsor
i-m
otor
1151Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Ago
sti e
t al.
[5]
RT-P
CR
+ ch
est C
TTh
rom
bocy
tope
nia
(101
× 10
9 /L,
refe
renc
e va
lue:
12
5–30
0 × 10
9 /L),
lym
phoc
ytop
enia
(0
.48 ×
109 /L
, ref
er-
ence
val
ue: 1
.1–3
.2 ×
10
9 /L)
Neg
ativ
e A
NA
, ant
i-D
NA
, c-A
NCA
, p-
AN
CA, n
ega-
tive
scre
enin
g fo
r Cam
pylo
-ba
cter
jeju
ni,
Myc
opla
sma
pneu
mon
iae,
Sal
-m
onel
la e
nter
ica,
C
MV,
HSV
1 a
nd
2, V
ZV, i
nflue
nza
viru
s A a
nd B
, H
IV, n
orm
al B
12
and
seru
m p
rote
in
elec
troph
ores
is
Incr
ease
d to
tal
prot
ein
(98
mg/
dl),
cell
coun
t: 2/
106 L
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Ant
ivira
l dru
gs (n
ot
spec
ifica
lly m
en-
tione
d)
Impr
ovem
ent,
disc
harg
ed h
ome
afte
r 30
days
Alb
erti
et a
l. [6
]RT
-PC
R +
ches
t CT
NA
NA
Incr
ease
d to
tal p
ro-
tein
(54
mg/
dl),
9 ce
lls/µ
l, ne
gativ
e SA
RS-
CoV
-2
PCR
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
+ m
echa
nica
l in
vasi
ve v
entil
atio
n
Lopi
navi
r/rito
navi
r, hy
drox
ychl
oroq
uine
24 h
afte
r adm
issi
on,
deat
h be
caus
e of
re
spira
tory
failu
re
Arn
aud
et a
l. [7
]RT
-PC
R +
ches
t CT
NA
Neg
ativ
e an
ti-ga
nglio
side
and
an
tineu
ral a
nti-
bodi
es, n
egat
ive
Cam
pylo
bact
er
Jeju
ni, H
IV,
syph
ilis,
CM
V,
EBV
sero
logy
Incr
ease
d to
tal p
ro-
tein
(1.6
5 g/
L), n
o pl
eyoc
itosi
s, ne
ga-
tive
olig
oclo
nal
band
s, ne
gativ
e SA
RS-
CoV
-2
PCR
, neg
ativ
e EB
V a
nd C
MV
RT
-PC
R
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
in,
cefo
taxi
me,
azi
thro
-m
ycin
e
Prog
ress
ive
impr
ovem
ent
Ass
ini e
t al.
[8]
RT-P
CR
Lym
phoc
ytop
enia
, in
crea
sed
LDH
an
d in
flam
mat
ion
mar
kers
; low
seru
m
albu
min
(2.9
mg/
dL)
NA
Nor
mal
tota
l pro
tein
le
vel,
incr
ease
d Ig
G/a
lbum
in ra
tio
(233
), ne
gativ
e SA
RS-
CoV
-2
PCR
, pre
senc
e of
ol
igoc
lona
l ban
ds
(bot
h in
seru
m
and
CSF
)
Dem
yelin
atin
g w
ith
sura
l spa
ring
AID
P
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
ro-
quin
e, a
rbid
ol,
riton
avir
and
lopi
-na
vir +
mec
hani
cal
inva
sive
ven
tilat
ion
5 da
ys a
fter I
VIG
, im
prov
emen
t of
swal
low
ing,
sp
eech
, ton
gue
mot
ility
, eye
lid
ptos
is a
nd st
reng
th
Ass
ini e
t al.
[8]
RT-P
CR
+ ch
est C
TLy
mph
ocyt
open
ia,
incr
ease
d LD
H a
nd
GG
T, le
ucoc
ytos
is,
low
seru
m a
lbum
in
(2.6
mg/
dL)
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies
Nor
mal
tota
l pro
tein
le
vel,
incr
ease
d Ig
G/a
lbum
in ra
tio
(170
), ne
gativ
e SA
RS-
CoV
-2
PCR
, pre
senc
e of
ol
igoc
lona
l ban
ds
(bot
h in
seru
m
and
CSF
)
Mot
or se
nsor
y ax
onal
, mus
cula
r ne
urog
enic
ch
ange
sA
MSA
N
NA
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
an
tiret
rovi
ral
ther
apy,
toci
li-zu
mab
+ tr
ache
os-
tom
y an
d as
siste
d ve
ntila
tion
5 da
ys a
fter I
VIG
, im
prov
emen
t of
vege
tativ
e sy
mp-
tom
s, pe
rsist
ence
of
hyp
orefl
exia
an
d rig
ht fo
ot d
rop
1152 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Big
aut e
t al.
[9]
RT-P
CR
+ ch
est C
TN
orm
al b
lood
cou
nt,
nega
tive
CR
PN
egat
ive
anti-
gang
liosi
de a
nti-
bodi
es, n
egat
ive
HIV
, Lym
e an
d sy
phili
s ser
olog
y
Incr
ease
d to
tal
prot
ein
(0.9
5 g/
L),
cell
coun
t: 1 ×
106 /L
, neg
a-tiv
e SA
RS-
CoV
-2
PCR
Dem
yelin
atin
gA
IDP
Spin
al:
Rad
icul
itis
and
plex
itis o
n bo
th b
rach
ial
and
lum
bar
plex
us; m
ul-
tiple
cra
nial
ne
uriti
s (in
III,
VI,
VII
, and
V
III n
erve
s)
IVIG
400
mg/
kg
(5 d
ays)
+ no
n-in
va-
sive
ven
tilat
ion
NA
Prog
ress
ive
impr
ovem
ent
Big
aut e
t al.
[9]
RT-P
CR
+ ch
est C
TIn
crea
sed
CR
PN
egat
ive
anti-
gang
liosi
de
antib
odie
s
Incr
ease
d to
tal p
ro-
tein
(1.6
g/L
), ce
ll co
unt:
6 × 10
6 /L,
nega
tive
SAR
S-C
oV-2
PC
R
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
NA
Slow
pro
gres
sive
im
prov
emen
t
Bra
cagl
ia e
t al.
[10]
RT-P
CR
(nor
mal
ch
est C
T)El
evat
ed C
PK (4
61
U/L
, nor
mal
< 14
5),
CR
P 5,
65 m
g/dL
(nor
mal
< 0.
5),
lym
phoc
yto-
pen
ia
(0·6
8 × 10
9 /L, n
orm
al
1·10
–4),
mild
incr
ease
of
LD
H (2
84 U
/L,
norm
al <
248)
, GO
T an
d G
PT (5
49 a
nd
547
U/L
, nor
-m
al <
35),
elev
atio
n of
IL-6
(11
pg/m
L,
norm
al <
5.9)
Neg
ativ
e an
ti-ga
nglio
side
ant
i-bo
dies
; neg
ativ
e m
icro
biol
ogic
te
sting
on
CSF
an
d se
rum
fo
r HSV
1-2,
EB
V, V
ZV,
CM
V, H
IV,
Myc
opla
sma
Pneu
mon
iae
and
Bor
relia
.
Incr
ease
d to
tal
prot
ein
(245
mg/
dL) a
nd in
crea
sed
cell
coun
t: 13
ce
lls/m
m3 , p
oly-
mor
phon
ucle
ate
61.5
%
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
rit
onav
ir, d
arun
avir
Impr
ovem
ent o
f UL
and
LL w
eakn
ess,
deve
lopm
ent o
f fa
cial
dip
legi
a
Cam
dess
anch
e et
al.
[11]
RT-P
CR
+ ch
est C
TN
AN
egat
ive
anti-
gang
liosi
des
antib
odie
s;
nega
tive
scre
en-
ing
for C
ampy
-lo
bact
er je
juni
, M
ycop
lasm
a pn
eum
onia
e,
Salm
onel
la
ente
rica,
CM
V,
EBV,
HSV
1-2,
V
ZV, I
nflue
nza
viru
s A &
B,
HIV
, and
hep
a-tit
is E
Incr
ease
d to
tal
prot
ein
(1.6
6 g/
L),
norm
al c
ell c
ount
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
+ m
echa
nica
l in
vasi
ve v
entil
atio
n
Oxy
gen
ther
apy,
pa
race
tam
ol,
low
mol
ecul
ar
wei
ght h
epar
in,
lopi
navi
r/rito
navi
r 40
0/10
0 m
g tw
ice
a da
y fo
r 10
days
NA
1153Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Cha
n et
al.
[12]
RT-P
CR
+ ch
est C
TPe
rsist
ent t
hrom
bocy
-to
sis (
max
imum
PC
68
8 ×1
09 /L),
elev
ated
d
-dim
er (1
.47
mg/
L)
NA
Incr
ease
d to
tal
prot
ein
(1.0
0 g/
L),
cell
coun
t: 4
× 10
6 /L (n
or-
mal
), ne
gativ
e SA
RS-
CoV
-2
PCR
Dem
yelin
atin
gA
IDP
Bra
in: b
ilate
ral
intra
cran
ial
faci
al n
erve
en
hanc
emen
t
IVIG
400
mg/
kg
(5 d
ays)
Empi
ric a
zith
rom
ycin
an
d ce
ftria
xone
Slig
ht im
prov
emen
t of
faci
al w
eak-
ness
, unc
hang
ed
para
esth
esia
Cha
n et
al.
[13]
RT-P
CR
NA
Neg
ativ
e an
ti-ga
nglio
side
s an
tibod
ies
Incr
ease
d to
tal
prot
ein
(226
mg/
dL),
leuc
ocyt
es:
3 ce
lls/m
m3 , g
lu-
cose
: 56
mg/
dL,
nega
tive
SAR
S-C
oV-2
PC
R
NA
Lum
bosa
cral
sp
ine:
no
path
olog
ical
fin
ding
s
5 se
ssio
ns o
f pla
sma-
pher
esis
NA
Reso
lutio
n of
dys
-ph
agia
, am
bula
-tio
n w
ith m
inim
al
assi
stan
ce 2
8 da
ys
afte
r sym
ptom
s on
set
Cha
n et
al.
[13]
RT-P
CR
NA
Elev
ated
GM
2 Ig
G/Ig
M a
nti-
bodi
es
Incr
ease
d to
tal
prot
ein
(67
mg/
dL),
leuc
ocyt
es:
1 ce
lls/m
m3 ,
gluc
ose
58 m
g/dL
, ne
gativ
e SA
RS-
CoV
-2 P
CR
NA
NA
Mec
hani
cal i
nvas
ive
vent
ilatio
n + 5
ses-
sion
s of p
lasm
aphe
re-
sis (
with
out b
enefi
t on
vent
ilatio
n) +
IVIG
NA
Pers
isten
ce o
f qu
adrip
ares
is
with
inte
rmitt
ent
auto
nom
ic d
ys-
func
tion,
slow
ly
wea
ned
from
the
vent
ilato
r
Coe
n et
al.
[14]
RT-P
CR
+ se
rolo
gyN
orm
al (n
ot sp
ecifi
ed)
Neg
ativ
e an
ti-ga
nglio
side
s an
tibod
ies;
ne
gativ
e m
enin
-gi
tis/e
ncep
halit
is
pane
l
Alb
umin
ocyt
olog
i-ca
l dis
soci
atio
n,
no in
trath
ecal
IgG
sy
nthe
sis,
nega
-tiv
e SA
RS-
CoV
-2
PCR
Dem
yelin
atin
g w
ith
sura
l spa
ring
AID
P
Bra
in: N
ASp
inal
: no
path
olog
ical
fin
ding
s
IVIG
400
mg/
kg
(5 d
ays)
NA
Rap
id im
prov
emen
t. Fr
om d
ay 1
1 fro
m
hosp
italis
atio
nRe
habi
litat
ion
Ebra
him
zade
h et
al.
[15]
RT-P
CR
+ ch
est C
TN
orm
al C
RP
(5 m
g/L)
, no
rmal
seru
m p
rote
in
imm
unoe
lect
roph
o-re
sis
Neg
ativ
e an
ti-G
Q1b
ant
ibod
-ie
s, ne
gativ
e sc
reen
ing
for
Cam
pylo
bact
er
jeju
ni, H
IV,
EBV,
CM
V,
influ
enza
viru
s (ty
pe A
and
B
), H
CV,
non
-re
activ
e V
DR
L
Incr
ease
d to
tal p
ro-
tein
(78
mg/
dL),
norm
al c
ell c
ount
(e
ryth
rocy
te =
0/m
m3 , l
euko
-cy
te =
4/m
m3 ),
norm
al g
luco
se
(70
mg/
dL)
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Spin
al: n
o pa
thol
ogic
al
findi
ngs
Non
eH
ydro
xych
loro
quin
e fo
r 5 d
ays
Impr
ovem
ent o
f m
uscl
e str
engt
h to
ne
ar n
orm
al a
fter
16 d
ays
1154 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Ebra
him
zade
h et
al.
[15]
RT-P
CR
+ ch
est C
TSl
ight
ly e
leva
ted
CR
P (3
4 m
g/L)
, nor
mal
se
rum
pro
tein
imm
u-no
elec
troph
ores
is
Neg
ativ
e an
ti-G
Q1b
ant
ibod
-ie
s, ne
gativ
e sc
reen
ing
for
Cam
pylo
bact
er
jeju
ni, H
IV,
EBV,
CM
V,
influ
enza
viru
s (ty
pe A
and
B
), H
CV,
non
-re
activ
e V
DR
L
NA
Dem
yelin
atin
gA
IDP
NA
IVIG
NA
Impr
ovem
ent o
f m
uscl
e str
engt
h in
all
extre
miti
es
afte
r 14
days
El O
tman
i et a
l. [1
6]RT
-PC
R +
ches
t CT
Lym
phoc
ytop
enia
(5
20/m
l)N
AIn
crea
sed
tota
l pr
otei
n (1
g/L
), no
rmal
cel
l cou
nt,
nega
tive
PCR
as
say
for
SAR
S-C
oV-2
Mot
or se
nsor
y ax
onal
AM
SAN
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
ro-
quin
e 60
0 m
g/da
y; a
zith
rom
ycin
50
0 m
g at
the
first
day,
then
250
mg
per d
ay
At w
eek
1 fro
m
adm
issi
on n
o si
g-ni
fican
t neu
rolo
gi-
cal i
mpr
ovem
ent
Este
ban
Mol
ina
et a
l. [1
7]RT
-PC
R +
ches
t X-r
ayLe
ucoc
yte
7400
/mm
3 , ly
mph
ocyt
e 24
00/
mm
3 . Hb
14 g
/dl.
PC 4
08,0
00/m
m3 ,
d-D
imer
556
ng/
ml.
Ferr
itin
544
ng/
ml,
CR
P 2.
04 m
g/dl
, Fi
brin
ogen
6.8
g/d
l
Neg
ativ
e ba
cter
io-
logi
cal a
nd v
iral
tests
Incr
ease
d to
tal
prot
ein
(86
mg/
dL),
cell
coun
t: 3x
106 /L
Dem
yelin
atin
gA
IDP
Bra
in: l
ep-
tom
enin
geal
en
hanc
emen
t in
mid
brai
n an
d ce
rvic
al
spin
e
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
az
ithro
myc
in,
ceftr
iaxo
n
Mot
or im
prov
emen
t bu
t per
siste
nce
of
para
esth
esia
Farz
i et a
l. [1
8]RT
-PC
R +
ches
t CT
Lym
phop
enia
(W
BC
:5.9
× 10
9 /L,
neut
roph
ils: 8
5%,
lym
phoc
yte:
15%
), el
evat
ed le
vels
of
CR
P, E
SR 6
9 m
m/h
NA
NA
Dem
yelin
atin
gA
IDP
NA
IVIG
(2 g
/kg
over
5
days
)Lo
pina
vir/r
itona
vir
and
hydr
oxyc
hlo-
roqu
ine
Impr
ovem
ent a
fter
3 da
ys, f
avor
able
ou
tcom
e
Fern
ánde
z–D
omín
guez
et a
l. [1
9]
RT-P
CR
NA
Neg
ativ
e an
ti-G
D1b
ant
i-bo
dies
, ne
gativ
e ot
her
anti-
gang
liosi
de
antib
odie
s
Incr
ease
d to
tal p
ro-
tein
(110
mg/
dL),
albu
min
ocyt
olog
i-ca
l dis
soci
atio
n
Dem
yelin
atin
gN
AB
rain
: no
path
olog
ical
fin
ding
s
IVIG
20
g/da
y (5
day
s)H
ydro
xych
loro
quin
e,
lopi
navi
r/rito
navi
rN
A
Fins
tere
r et a
l. [2
0]N
AN
AN
AN
AA
xona
lA
MA
NN
AIV
IGN
ARe
cove
ry
1155Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Fran
k et
al.
[21]
RT-P
CR
, + se
rolo
gy
(IgG
and
IgM
)W
BC
and
CR
P no
rmal
Neg
ativ
e he
patit
is
B a
nd C
, HIV
an
d V
DR
L te
sts
Two
CSF
ana
lysi
s 2
wee
ks a
part,
bo
th sh
owin
g no
r-m
al c
ell c
ount
and
C
SF b
ioch
emist
ry,
nega
tive
SAR
S-C
oV-2
PC
R,
nega
tive
PCR
for
HSV
1, H
SV2,
C
MV,
EBV
, V
ZV; Z
ika
viru
s;
Den
gue
viru
s an
d C
hiku
ngun
ya
viru
s
Axo
nal
AM
AN
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Spin
al: n
o pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Met
hylp
redn
isol
one,
az
ithro
myc
in,
albe
ndaz
ole
Som
e im
prov
e-m
ent,
wea
knes
s pe
rsist
ed
Gig
li et
al.
[22]
Che
st C
T +
sero
logy
(n
egat
ive
RT-P
CR
)N
AN
egat
ive
anti-
gang
liosi
de
antib
odie
s, ne
gativ
e PC
R
for i
nflue
nza
A
and
B v
iruse
s (n
asal
swab
)
Incr
ease
d to
tal p
ro-
tein
(192
.8 m
g/L)
, le
ucoc
ytes
: 2.6
ce
lls/µ
L, p
ositi
ve
Ig fo
r SA
RS-
CoV
-2, n
egat
ive
SAR
S-C
oV-2
PC
R
Dem
yelin
atin
gA
IDP
NA
NA
NA
NA
Gut
iérr
ez-O
rtiz
et a
l. [2
3]RT
-PC
RLy
mph
ocyt
es 1
000
cells
/UI,
CR
P 2.
8 m
g/dl
Posi
tive
anti-
GD
1b a
nti-
bodi
es, o
ther
an
ti-ga
nglio
side
an
tibod
ies
nega
tive
Incr
ease
d to
tal
prot
ein
(80
mg/
dl),
no le
ucoc
ytes
, gl
ucos
e62
mg/
dl, n
egat
ive
SAR
S-C
oV-2
PC
R
NA
NA
IVIG
400
mg/
kg
(5 d
ays)
NA
Afte
r 2 w
eeks
from
ad
mis
sion
com
-pl
ete
reso
lutio
n ex
cept
ano
smia
, ag
eusi
a
Gut
iérr
ez-O
rtiz
et a
l. [2
3]RT
-PC
RLe
ucop
enia
(310
0 ce
lls/µ
l)N
AIn
crea
sed
tota
l pr
otei
n (6
2 m
g/dl
), W
BC
: 2/μ
l (a
ll m
onoc
ytes
), gl
ucos
e: 5
0 m
g/dl
, ne
gativ
e SA
RS-
CoV
-2 P
CR
NA
NA
Non
ePa
race
tam
ol2
wee
ks la
ter c
om-
plet
e ne
urol
ogic
al
reco
very
with
no
ageu
sia,
com
plet
e ey
e m
ovem
ents
, an
d no
rmal
dee
p te
ndon
refle
xes
1156 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Hel
bok
et a
l. [2
4]C
hest
CT
+ se
rolo
gy
(rep
eate
d ne
gativ
e RT
-PC
R)
WB
C 8
.1G
/L (n
orm
al:
4.0–
10.0
G/L
), C
RP
2.3
mg/
dL, (
norm
al:
0.0–
0.5
mg/
dL),
fibrin
ogen
leve
l 65
0 m
g/dL
(nor
mal
: 21
0–40
0 m
g/dL
), LD
H 2
76 U
/L
(nor
mal
: 100
–250
U
/L),
eryt
hroc
yte
sedi
men
tatio
n ra
te
55 m
m/1
h
Neg
ativ
e PC
R
for C
MV,
EBV
, in
fluen
za v
irus
A/B
, Res
pira
-to
ry S
yncy
tial
Viru
s and
IgM
an
tibod
ies f
or
Chl
amyd
ia
pneu
mon
iae
and
Myc
opla
sma
pneu
mon
iae
Incr
ease
d to
tal
prot
ein
(64
mg/
dl),
cell
coun
t: 2
cells
/mm
3 , ser
um/
CSF
glu
cose
ratio
of
0.8
3, n
egat
ive
SAR
S-C
oV-2
PC
R, p
ositi
ve
anti-
SAR
S-C
oV-2
an
tibod
ies (
not
dete
rmin
ed
if in
trath
ecal
sy
nthe
sis o
r pas
-si
ve tr
ansf
er fr
om
bloo
d)
Dem
yelin
atin
g w
ith
sura
l spa
ring
AID
P
Spin
al: n
o pa
thol
ogic
al
findi
ngs
IVIG
30
g + pl
asm
a ex
chan
ge (4
cy
cles
) + m
echa
nica
l in
vasi
ve v
entil
atio
n
Non
eIm
prov
emen
t of
mus
cle
forc
es
with
reco
very
of
mob
ility
with
out
sign
ifica
nt h
elp
afte
r 8 w
eeks
Hut
chin
s et a
l. [2
5]RT
-PC
R +
ches
t CT
Lym
phop
enia
(abs
olut
e ly
mph
ocyt
e co
unt o
f 0.
7 K
/mm
3 )
Seru
m H
SV
IgG
and
IgM
. Re
spira
tory
vira
l pa
nel P
CR
neg
a-tiv
e N
egat
ive
GM
1, G
D1b
, an
d G
Q1b
IgG
an
d Ig
M),
aqua
-po
rin-4
rece
ptor
(I
gG),
HIV
1/2
, H
SV 1
/2 (I
gG
and
IgM
), C
MV
(I
gM),
Myc
o-pl
asm
a pn
eum
o-ni
ae (I
gG a
nd
IgM
), Bo
rrel
ia
burg
dorf
eri (
IgG
an
d Ig
M),
Bar-
tone
lla sp
ecie
s (I
gG a
nd Ig
M),
and
syph
ilis
(Ven
erea
l Dis
-ea
se R
esea
rch
Labo
rato
ry te
st)
Incr
ease
d to
tal p
ro-
tein
(49 m
g/dL
), no
rmal
glu
cose
le
vels
(65
mg/
dL),
no le
ukoc
ytes
Mix
ed d
emye
linat
-in
g an
d ax
onal
EM
G su
btyp
e un
know
n
Bra
in: e
nhan
ce-
men
t of t
he
faci
al a
nd
abdu
cens
ne
rves
bila
ter-
ally
, as w
ell
as th
e rig
ht
ocul
omot
or
nerv
eSp
inal
: no
path
olog
ical
fin
ding
s
Plas
ma
exch
ange
(5
cycl
es)
NA
Dis
char
ged
to in
pa-
tient
reha
bilit
atio
n
1157Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Julia
o C
aam
año
et a
l. [2
6]RT
-PC
RN
AN
AN
orm
al to
tal p
rote
in
(44
mg/
dL),
no
pleo
cyto
sis
Abs
ent b
link-
refle
xEM
G su
btyp
e un
know
n
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Ora
l pre
dnis
olon
eH
ydro
xych
loro
quin
e an
d lo
pina
vir/r
itona
-vi
r for
14
days
Min
imal
impr
ove-
men
t of m
uscl
e w
eakn
ess a
fter
2 w
eeks
Kha
lifa
et a
l. [2
7]RT
-PC
R +
ches
t X
-ray
+ ch
est C
TW
BC
5.5
× 10
3 , PC
35
6 × 10
3 , CR
P 0.
5 m
g/dL
(nor
mal
0.
0–0.
5), s
erum
fe
rriti
n 87
.3 n
g/m
l (n
orm
al 1
2.0–
150.
0),
elev
ated
d-D
imer
le
vels
0.7
2 m
g/L
(0.0
0–0.
49)
Neg
ativ
e sc
reen
ing
for:
influ
enza
A
and
B v
iruse
s;
influ
enza
A
viru
s sub
type
s H
1, H
3, a
nd
H5
incl
udin
g su
btyp
e H
5N1
of th
e A
sian
lin
eage
; par
ain-
fluen
za v
irus
type
s 1, 2
, 3, a
nd
4; re
spira
tory
sy
ncyt
ial v
irus
type
s A a
nd
B; a
deno
viru
s;
met
apne
umov
i-ru
s; rh
inov
irus;
en
tero
viru
s;
Cor
onav
irus
229E
, HK
U1,
N
L63,
and
O
C43
Cel
l cou
nt: 5
mm
3 , in
crea
sed
tota
l pr
otei
n (3
16.7
mg/
dL)
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Spin
al: e
nhan
ce-
men
t of t
he
caud
a eq
uina
ne
rve
root
s
IVIG
1 g
/kg
(2 d
ays)
Para
ceta
mol
, azi
thro
-m
ycin
, hyd
roxy
chlo
-ro
quin
e
Dis
char
ge to
hom
e af
ter 1
5 da
ys w
ith
clin
ical
and
ele
c-tro
phys
iolo
gica
l im
prov
emen
t
Kili
nc e
t al.
[28]
Feca
l PC
R +
sero
logy
NA
Neg
ativ
e an
ti-G
Q1b
ant
ibod
-ie
s, se
rolo
gic
tests
on
Borr
elia
bu
rgdo
rfer
i, sy
phili
s, C
ampy
-lo
bact
er je
juni
, C
MV,
hep
atiti
s E,
Myc
opla
sma
pneu
mon
iae
and
CM
V
Nor
mal
cel
l cou
nt,
norm
al p
rote
ins
Pred
omin
antly
de
mye
linat
ing
AID
P
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
2 g
/kg
(5 d
ays)
Non
ePe
rsist
ence
of m
ild
sym
ptom
s at t
he
disc
harg
e (a
fter
14 d
ays)
1158 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Lam
pe e
t al.
[29]
RT-P
CR
(neg
ativ
e ch
est X
-ray
)Sl
ight
ly in
crea
sed
CR
P (1
.92
mg/
dL)
Neg
ativ
e an
ti-ga
nglio
side
ant
i-bo
dies
; neg
ativ
e in
fluen
za a
nd
resp
irato
ry
sync
ytia
l viru
s
Incr
ease
d to
tal p
ro-
tein
(56
mg/
dL),
norm
al c
ell c
ount
(2
cel
ls/μ
L)
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
Non
eIm
prov
emen
t of
GB
S sy
mpt
oms
with
per
siste
nce
of g
ener
aliz
ed
arefl
exia
exc
ept
for l
eft b
icep
s re
flex,
dis
char
ge
afte
r 12
days
Lant
os e
t al.
[30]
RT-P
CR
NA
GM
1 an
tibod
ies
in th
e eq
uivo
cal
rang
e
NA
NA
Bra
in: e
nlar
ge-
men
t, pr
omin
ent
enha
ncem
ent
with
gad
o-lin
ium
, and
T2
hype
rinte
nse
sign
al o
f the
le
ft cr
ania
l ne
rve
III
IVIG
Hyd
roxy
chlo
roqu
ine
Impr
ovem
ent,
disc
harg
e af
ter
4 da
ys
Lasc
ano
et a
l. [3
1]RT
-PC
R +
ches
t X
-ray
+ po
sitiv
e Ig
M (I
gG p
ositi
vity
2
wee
ks la
ter)
WB
C 8
900
cells
/mm
3 ; ly
mph
ocyt
es 1
200
cells
/mm
3 ; PC
45,
500
cells
/mm
3
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies
Incr
ease
d to
tal
prot
ein
(60
mg/
dL),
leuc
ocyt
es: 3
ce
lls/μ
L, n
egat
ive
SAR
S-C
oV-2
PC
R
Dem
yelin
atin
gA
IDP
Spin
al: n
o ne
rve
root
ga
dolin
ium
en
hanc
emen
t
IVIG
400
mg/
kg
(5 d
ays)
+ m
echa
nica
lin
vasi
ve v
entil
atio
n
Azi
thro
myc
inIm
prov
emen
t of
tetra
pare
sis.
Abl
e to
stan
d up
w
ith a
ssist
ance
.
Lasc
ano
et a
l. [3
1]RT
-PC
R +
ches
t X-r
ayW
BC
330
0 ce
lls/
mm
3 ; lym
phoc
ytes
80
0 ce
lls/m
m3 ; P
C
119,
000
cells
/mm
3
NA
Nor
mal
tota
l pro
tein
(4
0 m
g/dl
), ce
ll co
unt:
2 ce
lls/μ
L
Mix
ed d
emye
linat
ing
(con
duct
ion
bloc
ks)
and
axon
al w
ith
sura
l spa
ring
patte
rnPr
edom
inan
tly A
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
Am
oxic
illin
, cla
rithr
o-m
ycin
Dis
mis
sal w
ith fu
ll m
otor
reco
very
. Pe
rsist
ence
of L
L ar
eflex
ia a
nd d
istal
pa
raes
thes
ia
Lasc
ano
et a
l. [3
1]RT
-PC
R +
ches
t X-r
ayW
BC
400
0 ce
lls/
mm
3 ; lym
phoc
ytes
60
0 ce
lls/m
m3 ; P
C
322,
000
cells
/mm
3
NA
Incr
ease
d to
tal
prot
ein
(140
mg/
dL),
cell
coun
t: 4
cells
/μL,
neg
ativ
e SA
RS-
CoV
-2
PCR
Dem
yelin
atin
g w
ith
sura
l spa
ring
patte
rnA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Spin
al c
ord:
lu
mbo
sacr
al
nerv
e ro
ot
enha
ncem
ent
IVIG
400
mg/
kg
(5 d
ays)
Am
oxic
illin
Impr
ovem
ent o
f te
trapa
resi
s and
ab
ility
to w
alk
with
ass
istan
ce.
Pers
isten
ce o
f neu
-ro
path
ic p
ain
and
dist
al p
arae
sthe
sia
1159Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Man
gano
tti e
t al.
[32]
RT-P
CR
+ ch
est C
TN
AN
egat
ive
anti-
gang
liosi
de
antib
odie
s ne
gativ
e se
rum
an
ti-H
IV, a
nti-
HBV
, ant
i-HC
V
antib
odie
s
Incr
ease
d to
tal
prot
ein
(74.
9 m
g/dL
), ne
gativ
e C
SF
PCR
for b
acte
ria,
fung
i, M
ycob
acte
-ri
um tu
berc
ulos
is,
Her
pes v
iruse
s, En
tero
viru
ses,
Japa
nese
B v
irus
and
Den
gue
viru
ses
NA
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kg
(5 d
ays)
Lopi
navi
r/rito
navi
r, hy
drox
ychl
oroq
uine
, an
tibio
tic th
erap
y,
oxyg
en su
ppor
t (3
5%)
Reso
lutio
n of
all
sym
ptom
s exc
ept
for m
inor
hyp
ore-
flexi
a at
the
LL
Man
gano
tti e
t al.
[33]
RT-P
CR
IL-1
: 0.2
pg/
ml
(< 0.
001
pg/m
l),
IL-6
: 113
.0 p
g/m
l (0
.8–6
.4 p
g/m
l),
IL-8
: 20.
0 pg
/ml
(6.7
–16.
2 pg
/ml),
TN
F-α:
16.
0 pg
/ml
(7.8
–12.
2 pg
/ml)
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies,
nega
-tiv
e H
IV, H
BV,
HC
V n
egat
ive
sero
logi
cal t
ests
fo
r aut
oim
mun
e di
sord
ers
Incr
ease
d to
tal
prot
ein
(52
mg/
dl),
leuc
ocyt
es: 1
ce
ll/m
m3 , n
ega-
tive
SAR
S-C
oV-2
PC
R
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
os
elta
miv
ir, d
aru-
navi
r, m
ethy
lpre
d-ni
solo
ne a
nd to
cili-
zum
ab +
mec
hani
cal
inva
sive
ven
tilat
ion
Impr
ovem
ent o
f m
otor
sym
ptom
s
Man
gano
tti e
t al.
[33]
RT-P
CR
IL-1
: 0.5
pg/
ml
(< 0.
001
pg/m
l),
IL-6
: 9.8
pg/
ml
(0.8
–6.4
pg/
ml),
IL
-8: 5
5.0
pg/m
l (6
.7–1
6.2
pg/m
l),
TNF-
α: 1
6.0
pg/m
l (7
.8–1
2.2
pg/m
l)
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies,
nega
-tiv
e H
IV, H
BV,
HC
V n
egat
ive
sero
logi
cal t
ests
fo
r aut
oim
mun
e di
sord
ers
Nor
mal
tota
l pro
tein
(4
0 m
g/dl
), le
uco-
cyte
s: 1
cel
l/mm
3 , ne
gativ
e SA
RS-
CoV
-2 P
CR
Mix
ed d
emy-
elin
atin
g an
d ax
onal
EM
G
subt
ype
unkn
own
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
lo
pina
vir/r
itona
vir,
met
hylp
redn
iso-
lone
+ m
echa
nica
l in
vasi
ve v
entil
atio
n
Impr
ovem
ent o
f m
otor
sym
ptom
s
Man
gano
tti e
t al.
[33]
RT-P
CR
NA
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies,
nega
-tiv
e H
IV, H
BV,
HC
V n
egat
ive
sero
logi
cal t
ests
fo
r aut
oim
mun
e di
sord
es
Incr
ease
d to
tal
prot
ein
(72
mg/
dL),
leuc
ocyt
es:
5 ce
ll/m
m3 , n
ega-
tive
SAR
S-C
oV-2
PC
R
Mai
nly
dem
yeli-
natin
gPr
edom
inan
tly
AID
P
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
lo
pina
vir/r
itona
vir,
met
hylp
redn
isol
one
Impr
ovem
ent
Man
gano
tti e
t al.
[33]
RT-P
CR
NA
NA
NA
Mix
ed d
emye
linat
-in
g an
d ax
onal
EM
G su
btyp
e un
know
n
NA
Met
hylp
redn
isol
one
60 m
g fo
r 5 d
ays
Met
hylp
redn
isol
one
Stat
iona
ry
1160 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Man
gano
tti e
t al.
[33]
RT-P
CR
IL-1
: 0.2
pg/
ml
(< 0.
001
pg/m
l),
IL-6
: 32.
7 pg
/ml
(0.8
–6.4
pg/
ml),
IL
-8: 1
7.8
pg/m
l (6
.7–1
6.2
pg/m
l),
TNF-
α :
11.1
pg/
ml (
7.8–
12.2
pg/
ml),
IL
-2R
: 120
3.0
pg/m
l (4
40.0
–143
5.0
pg/
ml),
IL-1
0: 4
.6
(1.8
–3.8
pg/
ml)
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies,
nega
-tiv
e H
IV, H
BV,
HC
V n
egat
ive
sero
logi
cal t
ests
fo
r aut
oim
mun
e di
sord
es
Incr
ease
d to
tal
prot
ein
(53
mg/
dL),
leuc
ocyt
es:
2 ce
ll/m
m3 , n
ega-
tive
SAR
S-C
oV-2
PC
R
Mix
ed d
emye
linat
-in
g an
d ax
onal
EM
G su
btyp
e un
know
n
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
lo
pina
vir/r
itona
vir,
met
hylp
redn
iso-
lone
, mer
open
em,
linez
olid
, cla
rithr
o-m
ycin
, fluc
ona-
zole
, dox
ycy-
clin
e + m
echa
nica
l in
vasi
ve v
entil
atio
n
Impr
ovem
ent
Mar
ta-E
ngui
ta e
t al.
[34]
RT-P
CR
+ ch
est C
TTh
rom
bocy
tope
nia,
d
-Dim
er e
leva
tion
NA
NA
NA
NA
NA
NA
Dea
th a
fter 1
0 da
ys
Moz
hdeh
ipan
ah e
t al.
[35]
RT-P
CR
(neg
ativ
e ch
est C
T)N
orm
al W
BC
, CR
P an
d ES
RN
AIn
crea
sed
tota
l pro
-te
in (1
39 m
g/dL
), no
rmal
cel
l cou
nt,
nega
tive
CSF
H
SV se
rolo
gy a
nd
gram
stai
n an
d cu
lture
Dem
yelin
atin
gA
IDP
NA
Plas
ma
exch
ange
(5
cycl
es)
NA
Sign
ifica
nt im
prov
e-m
ent o
f mus
cle
wea
knes
s afte
r 3
wee
ks, p
er-
siste
nce
of m
ild
bifa
cial
par
esis
Moz
hdeh
ipan
ah e
t al.
[35]
RT-P
CR
Nor
mal
WB
C, C
RP
and
ESR
NA
Alb
umin
ocyt
olog
i-ca
l dis
soci
atio
nN
AN
AIV
IG 4
00 m
g/kg
/day
(5
day
s)N
AC
ompl
ete
reco
very
, ex
cept
for t
he
pers
isten
ce o
f hy
pore
flexi
a
Moz
hdeh
ipan
ah e
t al.
[35]
RT-P
CR
+ ch
est C
TLe
ucoc
ytos
is ly
mph
o-pe
nia,
ele
vate
d ES
R
and
CR
P
NA
Incr
ease
d to
tal p
ro-
tein
(57
mg/
dL),
norm
al c
ell c
ount
an
d gl
ucos
e (n
ot
furth
er sp
ecifi
ed)
Axo
nal
AM
SAN
NA
IVIG
400
mg/
kg/d
ay
(3 d
ays)
Hyd
roxy
chl
oroq
uine
, lo
pina
vir/
riton
avir
Dea
th a
fter 3
day
s fro
m st
artin
g tre
at-
men
t with
IVIG
Moz
hdeh
ipan
ah e
t al.
[35]
RT-P
CR
+ ch
est C
TLe
ucoc
ytos
is, l
ymph
o-pe
nia,
ele
vate
d ES
R
and
CR
P
NA
Incr
ease
d to
tal p
rote
in
(89
mg/
dL),
nor-
mal
cel
l cou
nt a
nd
gluc
ose
(not
furth
er
spec
ified
)
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Hyd
roxy
chl
oroq
uine
, lo
pina
vir/
riton
avir
No
sign
ifica
nt c
lini-
cal i
mpr
ovem
ent
Nad
daf e
t al.
[36]
Posi
tive
SAR
S-C
oV-2
Ig
G (i
ndex
val
ue:
8.2,
nor
mal
< 0.
8)
and
IgA
+ ch
est C
T (n
egat
ive
RT-P
CR
)
Nor
mal
com
plet
ed
bloo
d co
unt,
elev
ated
d
-dim
er (6
90 n
g/m
L),
ferr
itin
(575
mcg
/L),
ESR
(26
mm
/h),
ala-
nine
am
inot
rans
fera
se
(73
U/L
)
Neg
ativ
e an
ti-ga
n-gl
iosi
de a
ntib
odie
s ne
gativ
e H
IV,
syph
ilis,
Wes
t N
ile v
irus,
Lym
e di
seas
e te
sting
, EB
V a
nd C
MV
se
rolo
gy c
onsi
st-en
t with
rem
ote
infe
ctio
n, n
egat
ive
para
neop
lasti
c ev
alua
tion
Incr
ease
d to
tal p
ro-
tein
(273
mg/
dL),
tota
l cel
ls c
ount
: 2/
mm
3, n
egat
ive
CSF
SA
RS-
CoV
-2 R
T-PC
R,
nega
tive
men
in-
gitis
/enc
epha
litis
pa
nel,
nega
tive
olig
oclo
nal b
ands
an
d Ig
G in
dex
Dem
yelin
atin
gA
IDP
Spin
e: sm
ooth
en
hanc
emen
t of
the
caud
a eq
uine
root
s
Plas
ma
exch
ange
(5
sess
ions
)H
ydro
xy c
hlor
oqui
ne,
zinc
, met
hylp
redn
i-so
lone
40
mg
bid
for
5 da
ys
Impr
ovem
ent o
f m
otor
and
gai
t ex
amin
atio
n. P
er-
siste
nce
of sl
ight
at
axia
with
out
requ
iring
gai
t aid
1161Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Ogu
z-A
kars
u et
al.
[37]
RT-P
CR
+ ch
est
MRT
+ ch
est C
TM
ild n
eutro
peni
a (1
.49
cells
/µL)
and
a h
igh
mon
ocyt
e pe
rcen
tage
(1
9.77
)
HIV
test
nega
tive
Nor
mal
tota
l pro
tein
(3
2.6
mg/
dL) w
ith
no le
ucoc
ytes
Dem
yelin
atin
g w
ith
sura
l spa
ring
patte
rnA
IDP
Cer
vica
l and
lu
mba
r an
d sp
ine:
as
ymm
etric
al
thic
keni
ng a
nd
hype
rinte
nsity
of
pos
t-gan
-gl
ioni
c ro
ots
supp
lyin
g th
e br
achi
al a
nd
lum
bar p
lex-
uses
in S
TIR
se
quen
ces
Plas
ma
exch
ange
(five
se
ssio
ns, o
ne e
very
ot
her d
ay)
Hyd
roxy
chlo
roqu
ine,
az
ithro
myc
inM
arke
d ne
urol
ogic
al
impr
ovem
ent a
fter
2 w
eeks
and
she
was
abl
e to
wal
k w
ithou
t ass
istan
ce
Otta
vian
i et a
l. [3
8]RT
-PC
R +
ches
t CT
Lym
phop
enia
, in
crea
sed
d-d
imer
, C
RP
and
CK
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies
Incr
ease
d to
tal
prot
ein
(108
mg/
dL),
cell
coun
t: 0
cells
/μL
Mai
nly
dem
yeli-
natin
gPr
edom
inan
tly
AID
P
NA
IVIG
400
mg/
kg
(5 d
ays)
Lopi
navi
r/rito
navi
r, hy
drox
ychl
oroq
uine
Prog
ress
ive
wor
sen-
ing
with
mul
ti-or
gan
failu
re
Padr
oni e
t al.
[39]
RT-P
CR
+ ch
est C
TW
BC
10.
41 ×
109 /L
(n
eutro
phils
8.
15 ×
109 /L
), no
r-m
al d
-dim
er
Neg
ativ
e sc
reen
ing
for M
ycop
lasm
a pn
eum
o-ni
a, C
MV,
Le
gion
ella
pn
eum
ophi
la,
Stre
ptoc
occu
s pn
eum
onia
e,
HSV
, VZV
, EB
V, H
IV-1
, Bo
rrel
ia
burg
dorf
eri;
auto
-ant
ibod
ies
not p
erfo
rmed
Incr
ease
d to
tal
prot
ein
(48
mg/
dl),
cell
coun
t: 1
× 10
6 /L
Mot
or se
nsor
y ax
onal
AM
SAN
NA
IVIG
400
mg/
kg
(5 d
ays)
+ m
echa
nica
l in
vasi
ve v
entil
atio
n
NA
At d
ay 6
from
ad
mis
sion
: IC
U
with
mec
hani
cal
inva
sive
ven
tila-
tion
Pate
rson
et a
l. [4
0]D
efini
te d
iagn
osis
(not
sp
ecifi
ed) (
norm
al
ches
t CT)
Incr
ease
d ne
utro
phils
an
d C
RP
NA
Incr
ease
d to
tal p
ro-
tein
(0.5
g/L
),le
ucoc
ytes
: 3 c
ells
/μL
(0–5
),
Dem
yelin
atin
gA
IDP
NA
IVIG
+ m
echa
nica
l in
vasi
ve v
entil
atio
nN
one
17 d
ays o
f hos
-pi
talis
atio
n, a
t di
scha
rge
able
to
wal
k 5
m (a
cros
s an
ope
n sp
ace)
bu
t inc
apab
le o
f m
anua
l wor
k/ru
nnin
g
Pate
rson
et a
l. [4
0]D
efini
te d
iagn
osis
(not
sp
ecifi
ed) (
norm
al
ches
t CT)
Incr
ease
d C
RP
and
fibrin
ogen
NA
Incr
ease
d to
tal p
ro-
tein
(0.6
g/L
)le
ucoc
ytes
: 2 c
ells
/μL
(0-5
), G
luco
se
3.4
(mm
ol/L
; 2.
2-4.
2)
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
Mec
hani
cal i
nvas
ive
vent
ilatio
n46
day
s (on
goin
g)
of h
ospi
talis
a-tio
n, st
ill c
ritic
al
and
requ
iring
ve
ntila
tion
1162 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Pate
rson
et a
l. [4
0]D
efini
te d
iagn
osis
(not
sp
ecifi
ed) (
norm
al
ches
t CT)
Not
sign
ifica
nt fi
ndin
gsN
AIn
crea
sed
tota
l pro
-te
in (0
.9 g
/L)
leuc
ocyt
es: <
1 ce
lls/
μL (0
-5),
Glu
cose
3.
7 (m
mol
/L;
2.2-
4.2)
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
IVIG
NA
7 da
ys (o
ngoi
ng) o
f ho
spita
lisat
ion,
ab
le to
wal
k 5
m
(acr
oss a
n op
en
spac
e) b
ut in
ca-
pabl
e of
man
ual
wor
k/ru
nnin
g
Payb
ast e
t al.
[41]
RT-P
CR
NA
NA
Incr
ease
d to
tal p
ro-
tein
(139
mg/
dL),
norm
al g
luco
se
and
cell
coun
t, no
rmal
CSF
vira
l se
rolo
gy, n
egat
ive
gram
stai
n an
d cu
lture
Mix
ed d
emye
linat
-in
g an
d ax
onal
EM
G su
btyp
e un
know
n
NA
5 se
ssio
ns o
f the
rape
utic
pl
asm
a ex
chan
ge,
intra
veno
us b
olus
of
labe
talo
l to
cont
rol
sym
path
etic
ner
vous
sy
stem
ove
r-rea
ctiv
ity
Hyd
roxy
chlo
roqu
ine
sulp
hate
200
mg
two
times
per
day
fo
r a w
eek
Pers
isten
ce o
f ge
nera
lized
hy
pore
flexi
a,
decr
ease
d lig
ht
touc
h se
nsat
ion
in
dist
al li
mbs
, mild
bi
late
ral f
acia
l pa
resi
s, sy
mpa
-th
etic
ove
r-rea
c-tiv
ity su
cces
sful
ly
cont
rolle
d w
ith
labe
talo
l,
Payb
ast e
t al.
[41]
RT-P
CR
NA
NA
Alb
umin
ocyt
olog
i-ca
l dis
soci
atio
nN
AN
AIV
IG 2
0 g
(5 d
ays)
Hyd
roxy
chlo
roqu
ine
sulp
hate
200
mg
two
times
per
day
fo
r a w
eek
Pers
isten
ce o
f ge
nera
lized
hy
pore
flexi
a an
d de
crea
sed
light
to
uch
sens
atio
n in
di
stal
lim
bs
Pfeff
erko
rn e
t al.
[42]
RT-P
CR
+ ch
est C
TN
AN
egat
ive
anti-
gang
liosi
des
antib
odie
s
At a
dmis
sion
: Nor
-m
al to
tal p
rote
in,
cell
coun
t: 9/
µL,
nega
tive
SAR
S-C
oV-2
PC
RA
t day
13t
h:
incr
ease
d to
tal p
rote
in
(10.
231
mg/
L),
norm
al c
ell c
ount
Dem
yelin
atin
gA
IDP
Spin
al: m
assi
ve
sym
met
rical
co
ntra
st en
hanc
emen
t of
the
spin
al
nerv
e ro
ots
at a
ll le
vels
of
the
spin
e in
clud
ing
the
caud
a eq
uina
. A
nter
ior a
nd
poste
rior
nerv
e ro
ots
wer
e eq
ually
aff
ecte
d
IVIG
30
g (5
day
s) +
mec
hani
-ca
l inv
asiv
e ve
ntila
tion +
plas
ma
exch
ange
NA
At d
ay 3
1 fro
m
adm
issi
on: m
otor
im
prov
emen
t w
ith re
gres
sion
of
faci
al a
nd h
ypo-
glos
sal p
ares
is
but s
till n
eede
d m
echa
nica
l ven
-til
atio
n
Ran
a et
al.
[43]
RT-P
CR
NA
NA
NA
Dem
yelin
atin
g w
ith
sura
l spa
ring
AID
P
Thor
acic
and
lu
mba
r spi
ne:
no e
vide
nce
of
mye
lopa
thy
or
radi
culo
path
y
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
ine
and
azith
rom
ycin
On
day
4 re
spira
tory
im
prov
emen
t, on
da
y 7
reha
bilit
a-tio
n
1163Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Reye
s-B
ueno
et a
l. [4
4]Se
rolo
gy (n
egat
ive
RT-P
CR
)N
AN
egat
ive
anti-
gang
liosi
de
antib
odie
s
Incr
ease
d to
tal
prot
ein
(70
mg/
dl),
cell
coun
t: 5
cells
/µl,
albu
-m
inoc
ytol
ogic
al
diss
ocia
tion
Dem
yelin
atin
g w
ith
alte
ratio
n of
the
Blin
k-Re
flex.
Fur
-th
er E
MG
: pol
yra-
dicu
lone
urop
athy
w
ith p
roxi
mal
and
br
ains
tem
invo
lve-
men
tA
IDP
NA
IVIG
400
mg/
kg
(5 d
ays)
+ G
abap
entin
NA
Afte
r the
18t
h da
y pr
ogre
ssiv
e im
prov
emen
t of
faci
al a
nd li
mb
pare
sis,
dipl
opia
an
d pa
in. C
onse
-qu
ent n
euro
logi
cal
reha
bilit
atio
n
Riv
a et
al.
[45]
Che
st C
T +
sero
logy
(n
egat
ive
RT-P
CR
)N
o pa
thol
ogic
al fi
nd-
ings
Neg
ativ
e an
ti-ga
nglio
side
an
tibod
ies
Nor
mal
tota
l pro
tein
an
d ce
lls; n
egat
ive
PCR
for S
AR
S-C
oV2,
EBV
, C
MV,
VZV
, HSV
1–
2, H
IV
Dem
yelin
atin
g w
ith
sura
l spa
ring
AID
P
Bra
in: N
ASp
inal
: no
path
olog
ical
fin
ding
s
IVIG
400
mg/
kg
(5 d
ays)
Non
eSl
owly
impr
ovem
ent
afte
r the
10t
h da
y
Sanc
ho-S
alda
ña e
t al.
[46]
RT-P
CR
+ ch
est
X-R
ayN
AN
egat
ive
anti-
gang
liosi
de
antib
odie
s
Incr
ease
d to
tal
prot
ein
(0.8
6 g/
L),
cell
coun
t: 3
leuc
ocyt
es
Dem
yelin
atin
gA
IDP
Who
le sp
ine:
br
ains
tem
an
d ce
rvic
al
men
inge
al
enha
ncem
ent
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
az
ithro
myc
inRe
cove
ring
by d
ay 7
af
ter t
he o
nset
of
wea
knes
s.
Sche
idl e
t al.
[47]
RT-P
CR
No
path
olog
ical
find
-in
gsN
egat
ive
Cam
pylo
bact
er
Jeju
ni a
nd B
or-
relia
sero
logy
, ne
gativ
e A
NA
, an
ti-D
NA
, c-
AN
CA,p
-A
NCA
Incr
ease
d to
tal
prot
ein
(140
g/L
), al
bum
inoc
ytol
ogi-
cal d
isso
ciat
ion
Dem
yelin
atin
gA
IDP
Bra
in: N
AC
ervi
cal s
pine
: no
pat
holo
gi-
cal fi
ndin
gs
IVIG
400
mg/
kg
(5 d
ays)
Non
eC
ompl
ete
reco
very
Seda
ghat
et a
l. [4
8]RT
-PC
R +
ches
t CT
Incr
ease
d W
BC
14
.6 ×
103 (n
eu-
troph
ils 8
2.7%
, ly
mph
ocyt
es 1
0.4%
) an
d C
RP
NA
NA
Mot
or se
nsor
y A
xona
lA
MSA
N
Bra
in: n
o pa
thol
ogic
al
findi
ngs
Spin
al: t
wo
cerv
ical
in
terv
erte
bral
di
sc h
erni
a-tio
ns
IVIG
400
mg/
kg
(5 d
ays)
Hyd
roxy
chlo
roqu
ine,
lo
pina
vir/r
itona
vir,
azith
rom
ycin
Not
repo
rted
Sidi
g et
al.
[49]
RT-P
CR
+ ch
est C
TN
AN
AN
one
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
thol
ogic
al
findi
ngs
NA
NA
Dea
th a
fter 7
day
s;
beca
use
of p
ro-
gres
sive
resp
ira-
tory
failu
re
1164 Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)
Arti
cle
COV
ID-1
9 di
agno
sis
Blo
od fi
ndin
gsA
uto-
antib
odie
s an
d sc
reen
ing
for
mos
t com
mon
G
BS
caus
es
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Su e
t al.
[50]
RT-P
CR
+ ch
est X
-ray
WB
C 1
2,00
0 ce
lls/µ
lN
egat
ive
anti-
ga
nglio
side
G
M1,
GD
1b a
nd
GQ
1b a
ntib
od-
ies,
acet
ylch
o-lin
e re
cept
or
bind
ing,
vo
ltage
-gat
ed
calc
ium
cha
nnel
, an
tinuc
lear
and
A
NCA
Incr
ease
d to
tal p
ro-
tein
(313
mg/
dL),
WB
C: 1
cel
l
Dem
yelin
atin
gA
IDP
NA
IVIG
2gm
/kg
(for
4 da
ys)
Non
eO
n da
y 28
per
sis-
tenc
e of
seve
re
wea
knes
s
Tiet
et a
l. [5
1]RT
-PC
REl
evat
ed la
ctat
e on
ve
nous
blo
od g
as
(3.3
mm
o/L)
, mild
ly
elev
ated
CR
P (2
0 m
g/L)
. Nor
mal
W
BC
, sod
ium
, po
tass
ium
and
rena
l fu
nctio
n.
NA
Incr
ease
d to
tal p
ro-
tein
(> 1.
25 g
/L),
cell
coun
t 1x1
06 /L
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
Non
eRe
solu
tion
of fa
cial
di
pleg
ia, i
mpr
oved
up
per a
nd lo
wer
lim
bs w
eakn
ess;
ab
le to
mob
ilize
un
assi
sted
11
wea
ks a
fter n
eu-
rore
habi
litat
ion
Tosc
ano
et a
l. [5
2]RT
-PC
R +
Che
st C
T +
sero
logy
Lym
phoc
ytop
enia
, in
crea
sed
CR
P, L
DH
, ke
tonu
ria
Neg
ativ
e an
ti-ga
ngli-
osid
e an
tibod
ies
Day
2: n
orm
al to
tal
prot
ein,
no
cells
, ne
gativ
e SA
RS-
CoV
-2 P
CR
Day
10:
incr
ease
d to
tal p
rote
in (1
01)
mg/
dl, c
ell c
ount
: 4/
mm
3 , neg
ativ
e SA
RS-
CoV
-2 P
CR
Axo
nal w
ith su
ral
spar
ing
AM
SAN
Bra
in: n
o pa
tho-
logi
cal fi
ndin
gsSp
inal
: Enh
ance
-m
ent o
f cau
dal
nerv
e ro
ots
IVIG
400
mg/
kg (2
cy
cles
) + te
mpo
rary
m
echa
nica
l non
-in
vasi
ve v
entil
atio
n
Para
ceta
mol
At w
eek
4 pe
rsis
-te
nce
of se
vere
U
L w
eakn
ess,
dysp
hagi
a, a
nd L
L pa
rapl
egia
Tosc
ano
et a
l. [5
2]RT
-PC
R (n
egat
ive
ches
t CT)
Lym
phoc
ytop
enia
; in
crea
sed
ferr
itin,
CR
P,
LDH
NA
Incr
ease
d to
tal p
rote
in
(123
mg/
dl),
no
cells
, ne
gativ
e SA
RS
-CoV
-2 P
CR
Mot
or se
nsor
y ax
onal
w
ith su
ral s
parin
gA
MSA
N
Bra
in:
enha
ncem
ent
of fa
cial
ner
ve
bila
tera
llySp
inal
: no
pa
thol
ogic
al
findi
ngs
IVIG
400
mg/
kgA
mox
ycill
inA
t wee
k 4
im
prov
emen
t of
ata
xia
an
d m
ild
impr
ovem
ent
of f
acia
l w
eakn
ess
Tosc
ano
et a
l. [5
2]RT
-PC
R +
ches
t CT
Lym
phoc
ytop
enia
; in
crea
sed
CR
P, L
DH
, ke
tonu
ria
Neg
ativ
e an
ti-ga
ngli-
osid
e an
tibod
ies
Incr
ease
d to
tal p
rote
in
(193
mg/
dl),
no
cells
, neg
ativ
e SA
RS-
CoV
-2 P
CR
Mot
or a
xona
lA
MA
NB
rain
: no
path
o-lo
gica
l find
ings
Spin
al: e
nhan
ce-
men
t of c
auda
l ne
rve
root
s
IVIG
400
mg/
kg (2
cy
cles
) + m
echa
nica
l in
vasi
ve v
entil
atio
n
Azy
thro
mic
inIC
U a
dmis
sion
du
e to
re
spira
tory
fa
ilure
and
te
trapl
egia
. A
t wee
k 4
still
crit
ical
1165Journal of Neurology (2021) 268:1133–1170
1 3
Tabl
e 1
(con
tinue
d)A
rticl
eCO
VID
-19
diag
nosi
sB
lood
find
ings
Aut
o-an
tibod
ies
and
scre
enin
g fo
r m
ost c
omm
on
GB
S ca
uses
CSF
find
ings
Elec
troph
ysio
l-og
y: N
euro
path
y ty
pe a
nd G
BS
elec
-tro
phys
iolo
gic
subt
ype
MR
I (br
ain
and
spin
al)
Man
agem
ent a
nd th
erap
yO
utco
me
GB
SCO
VID
-19
Tosc
ano
et a
l. [5
2]RT
-PC
R +
sero
logy
(n
egat
ive
ches
t CT)
Lym
phoc
ytop
enia
; in
crea
sed
CR
P,
keto
nuria
NA
Nor
mal
pro
tein
, no
cells
, neg
ativ
e SA
RS-
CoV
-2 P
CR
Dem
yelin
atin
gA
IDP
Bra
in: n
o pa
tho-
logi
cal fi
ndin
gsSp
inal
: no
path
o-lo
gica
l find
ings
IVIG
400
mg/
kgN
one
At w
eek
4 m
ild
impr
ovem
ent i
n U
L bu
t una
ble
to
stan
d
Tosc
ano
et a
l. [5
2]C
hest
CT
+ se
rolo
gy
(neg
ativ
e RT
-PC
R
in n
asop
hary
ngea
l sw
ab a
nd B
AL)
Lym
phoc
ytop
enia
; in
crea
sed
CR
P, L
DH
Neg
ativ
e an
ti-ga
ngli-
osid
e an
tibod
ies;
ne
gativ
e sc
reen
ing
for C
ampy
loba
c-te
r jej
uni,
EBV,
C
MV,
HSV
, VZV
, in
fluen
za, H
IV
Nor
mal
tota
l pro
tein
(4
0 m
g/dL
), w
hite
ce
ll co
unt 3
/mm
3 ; ne
gativ
e SA
RS-
CoV
-2 P
CR
Dem
yelin
atin
gA
IDP
Bra
in: N
ASp
inal
: no
path
o-lo
gica
l find
ings
IVIG
400
mg/
kg +
plas
ma
exch
ange
+ m
echa
ni-
cal i
nvas
ive
vent
ila-
tion +
ente
ral n
utrit
ion
Non
eA
t wee
k 4
flacc
id
tetra
pleg
ia, d
ys-
phag
ia, v
entil
atio
n de
pend
ent
Vela
yos G
alán
et a
l. [5
3]RT
-PC
R +
ches
t X-r
ayN
AN
AN
AD
emye
linat
ing
AID
PN
AIV
IG 4
00 m
g/kg
(5
day
s)H
ydro
xych
loro
quin
e,
lopi
navi
r/rito
navi
r, am
oxic
illin
, cor
ti-co
stero
ids +
low
-flo
w o
xyge
n th
erap
y
NA
Vira
ni e
t al.
[54]
rt-pc
r + ch
est m
rtW
BC
8.6
× 1
03 ; H
b 15
.4 g
/dl;
PC
211
× 10
3 ; pro
calc
i-to
nin:
0.1
5 ng
/ml
NA
NA
NA
Bra
in: N
ASp
inal
: no
path
olog
ical
fin
ding
s
IVIG
400
mg/
kg
(5 d
ays)
+ m
echa
nica
l in
vasi
ve v
entil
atio
n (4
day
s)
Hyd
roxy
chlo
roqu
ine
400
mg
bid
for
first
2 do
ses,
then
20
0 m
g bi
d fo
r 8
dose
s
At d
ay 4
of I
VIG
: lib
erat
ion
from
m
echa
nica
l ven
ti-la
tion,
reso
lutio
n of
UL
sym
ptom
s, pe
rsist
ence
of L
L w
eakn
ess.
Sent
to
a re
habi
litat
ion
faci
lity
Web
b et
al.
[55]
RT-P
CR
+ ch
est
X-r
ay +
ches
t CT
Lym
phop
enia
(0
.9 ×
109 /L
), th
rom
bocy
tosi
s (4
90 ×
109 /L
) rai
sed
CR
P (2
5 m
g/L)
Neg
ativ
e A
NA
, A
NCA
, ant
i-ga
nglio
side
an
tibod
ies,
syph
ilis s
erol
ogy
HIV
, hep
atiti
s B
and
hepa
titis
C
Incr
ease
d to
tal p
rote
in
(0.5
1 g/
L), n
orm
al
gluc
ose
and
cell
coun
t, ne
gativ
e SA
RS-
CoV
-2 P
CR
, ne
gativ
e vi
ral P
CR
Dem
yelin
atin
gA
IDP
NA
IVIG
400
mg/
kg/d
ay
(5 d
ays)
+ M
echa
nica
l in
vasi
veve
ntila
tion
Co-
amox
icla
vA
fter 1
wee
k in
IC
U: n
o ox
ygen
re
quire
men
t and
ve
ntila
tion
Zhao
et a
l. [5
6]RT
-PC
R +
ches
t CT
WB
C 0
.52
× 10
9 ; PC
11
3 ×
109 /L
NA
Incr
ease
d to
tal p
rote
in
(124
mg/
dL),
cell
coun
t 5 ×
106 /L
Dem
yelin
atin
gA
IDP
NA
IVIG
(dos
ing
not
repo
rted)
Arb
idol
, lop
inav
ir/
riton
avir
At d
ay 3
0 re
solu
tion
of n
euro
logi
cal
and
resp
irato
ry
sym
ptom
s
AID
P, a
cute
infla
mm
ator
y de
mye
linat
ing
poly
neur
opat
hy; A
MA
N, a
cute
mot
or a
xona
l neu
ropa
thy;
AM
SAN
, acu
te m
otor
sens
ory
axon
al n
euro
path
y; A
NA
, ant
inuc
lear
ant
ibod
ies;
AN
CA, a
nti-
neut
roph
il cy
topl
asm
ic a
ntib
odie
s; B
AL,
bro
ncho
alve
olar
lava
ge; C
K, c
reat
ine
kina
se; C
MV,
cyt
omeg
alov
irus;
CO
PD, c
hron
ic o
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1166 Journal of Neurology (2021) 268:1133–1170
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GBS, the same finding was less frequently reported [84]. However, caution should be warranted in the interpretation of these results, given that MRI findings might have been underestimated, due to lack of a sufficient number of exams in the context of pandemic-imposed restrictions in the rou-tine clinical setting.
Regarding the distribution of GBS electrophysiological variants, our analysis showed that COVID-19-associated GBS manifests prevalently with AIDP and, to a lesser extent, with AMSAN and AMAN, in line with classic GBS in West-ern countries [66, 85]. Conversely, the observation of posi-tive anti-GD1b antibodies in one COVID-19-related MFS patient and negative anti-ganglioside antibodies in other five cases appear in discordance with the high prevalence (≈ 90%) of anti-GQ1b antibodies among non-COVID-19 MFS cases [86], and may suggest different immune-medi-ated mechanisms. However, these results could not be gen-eralized until a wider population would be tested.
In analogy to classic GBS, approximately one-fifth of COVID-19-associated GBS subjects required mechanical ventilation during hospitalisation [87]. In this regard, cases with no improvement or unfavorable outcome showed, in comparison to those with a good prognosis, an older age, confirming similar findings both in classic GBS [58, 88] and in COVID-19 [89], and a slightly higher frequency (with-out reaching a statistical significance) of past or concurrent COVID-19 pneumonia. However, given the short follow-up time in most cases, we could not reach a definite conclu-sion on the impact of past or concurrent COVID-19 restric-tive syndrome due to pneumonia on the prognosis of GBS patients. Future prospective studies are needed to clarify this issue. Moreover, given that also preceding diarrhea (mostly caused by Campylobacter Jejuni infection) is a strong negative prognostic factor in classic GBS [57, 88], further prospective studies are needed to compare the severity of GBS related to COVID-19 to that associated with C. jejuni. Finally, in the context of respiratory failure and ventilation associated with COVID-19, the differential diagnosis should always take into consideration critical illness neuropathy and myopathy, which tend to develop later during the critical course [90]. Despite these findings, approximately one-third of COVID-19-related GBS patients showed no clinical and/or radiological evidence of pneumonia, providing evidence that GBS may also develop in the context of a paucisymp-tomatic or even asymptomatic COVID-19. However, given that among the GBS population only two asymptomatic COVID-19 patients were reported to date, we may spec-ulate that, in most cases, a certain degree of lung injury (even minimal) or at least hematic dissemination (e.g., fever underlying significant viral load) is necessary to trigger the immuno-mediated process through lymphocytic recognition of self-antigens or molecular mimicry.
the notion of a prominent post-infectious immune-mediated mechanism. However, in this context, the massive release of cytokines in COVID-19 may also contribute to the amplifi-cation of the dysimmune process underlying GBS [76, 77]. In this regard, the increase of blood inflammatory markers (e.g., CRP, IL-6, TNF-α, IL-1, etc.) in GBS tested cases may reinforce the hypothesis of a systemic inflammatory storm in COVID-19 [76, 77]. However, given the limited data, we could not perform an accurate analysis of the distribution and, eventually, prognostic value of inflammatory markers in COVID-19-associated GBS. Moreover, we cannot exclude that in cases with GBS developing before or together with COVID-19 symptoms, the disease might have progressed sub-clinically in the early phase to manifest afterwards with its typical systemic clinical picture. Indeed, two cases [10, 12], who tested positive for SARS-CoV-2, never developed COVID-19 respiratory or systemic symptoms and one of them showed an asymptomatic pneumonia at chest-CT [12]. However, only more extensive epidemiological and transla-tional studies, with the aim to compare the characteristics of GBS associated or not with COVID-19, could clarify these issues.
In our population, most common clinical manifestations and distribution of clinical variants resemble those of clas-sic GBS confirming the predominance of the sensorimotor syndrome compared to MFS and other rare variants [57–59, 66]. Similarly, the results of CSF analysis reflected typical neurochemical findings in non-COVID-19 GBS. In the lat-ter, elevated CSF proteins and pleocytosis were described in about 50–80% [57, 78] and 11–15% cases, respectively [58, 79, 80], largely overlapping with the percentages in our cohort. In this regard, the mostly normal cell count, together with the absence of SARS-CoV-2 RNA in all tested CSF samples [6–9, 12–14, 16, 21–24, 31, 33, 36, 42, 44, 52, 55], makes the possibility of a direct invasion from SARS-CoV-2 into the nerve roots with intrathecal viral replication less probable. However, a possible bias might rely on the lack of systematic data concerning the latency between symp-tom onset and CSF sampling in COVID-19 GBS cases. On another issue, in a further case of MFS associated with-COVID-19, who came to our attention, we observed the absence of intrathecal synthesis of SARS-CoV-2 antibod-ies together with a massive increase of CSF phosphoryl-ated neurofilament heavy chain (pNfH) and serum neuro-filament light chain (NfL) proteins, supporting the role of neurochemical markers as easily implementable tools for the detection of nervous system affection in COVID-19-related diseases [81, 82].
At variance with CSF findings, we found a discrepancy concerning MRI findings between classic GBS and COVID-19-related GBS. Specifically, while most cases of the for-mer group showed typically spinal root enhancement at MRI [83], in the latter group, in analogy with Zika-associated
1167Journal of Neurology (2021) 268:1133–1170
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Major strengths of our review are the inclusion of a high number of patients, together with an in-depth analysis of the clinical and diagnostic features of COVID-19-associated GBS. We are aware that selection bias might have occurred, given that most reported cases to date have been described mostly in Europe (47 out of 73) and during COVID-19 high-est spreading. Therefore, future extensive epidemiological studies are necessary to ascertain the nature of the associa-tion between COVID-19 and GBS (causal or coincidental). Moreover, we cannot exclude the possibility that at least some of the cases represent instances of CIDP, given the frequent absence of a follow-up longer than 2 months. On another issue, the low but possible evidence of an epidemio-logical link between vaccines and GBS development [57, 58] should aware the clinicians of the possible occurrence of GBS after COVID-19 vaccination in the long-term future.
In conclusion, based on the systematic review of 73 cases, we showed that the clinical picture of COVID-19-associ-ated GBS seems to resemble that of classic GBS or Zika-associated GBS. Moreover, the chronological evolution, the response to IVIG, and the absence of SARS-CoV-2 RNA in CSF may suggest a prominent post-infectious immune-mediated mechanism rather than a para-infectious one. Although most cases were symptomatic for COVID-19,
the preliminary report of a few patients without respira-tory or systemic symptoms raises a significant healthcare issue, namely the importance of SARS-CoV-2 testing in all patients with suspected GBS during the pandemic, with the aim to provide an eventual rapid case isolation. Neverthe-less, only further analyses on more comprehensive cohorts could help in clarifying better all these issues.
Acknowledgements Open Access funding provided by Projekt DEAL. This work was in part supported by a COVID-19 grant from the state Baden-Württemberg.
Authors’ contributions Conceptualization: all authors; methodology, formal analysis, and investigation: Samir Abu-Rumeileh, Ahmed Abdelhak, and Matteo Foschi; writing—original draft preparation: all authors; figure preparation: Matteo Foschi; writing—review and editing: all authors; supervision: Markus Otto and Hayrettin Tumani.
Compliance with ethical standards
Conflicts of interest The authors declare that they have no conflict of interest related to the content of this article.
Ethical standard For the present study, no authorization to an Eth-ics Committee was asked, because the original reports, nor this work, provided any personal information of the patients.
Fig. 1 Temporal and spatial distribution of reported cases with COVID-19-associated Guillain–Barré syndrome in literature from 1st January until 20th July 2020. The x-axis shows the number of described patients. The y-axis illustrates the countries of provenience
of the cases. In each line, different colours represent the months of April, May, June, and July (* until 20th July) 2020, in which the cases were published. Abbreviations: UK, United Kingdom, USA, United States of America
1168 Journal of Neurology (2021) 268:1133–1170
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