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Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2022 Nov 16;123(1):9–44. doi: 10.1007/s13760-022-02137-2

A review of the potential neurological adverse events of COVID-19 vaccines

Zeinab Mohseni Afshar 1, Akanksha Sharma 2, Arefeh Babazadeh 3, Ali Alizadeh-Khatir 4, Terence T Sio 5, Mohamad Ali Taghizadeh Moghadam 6, Ali Tavakolli Pirzaman 7, Ahmadreza Mojadad 7, Rezvan Hosseinzadeh 7, Mohammad Barary 8,9,, Soheil Ebrahimpour 3,
PMCID: PMC9668235  PMID: 36385246

Abstract

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain–Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell’s palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

Keywords: COVID-19, Vaccine, Adverse event, Neurologic, SARS-CoV-2

Introduction

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae [1, 2]. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG), and Guillain–Barre syndrome (GBS) [35]. In addition, after vaccination, hypercoagulability and a pro-thrombotic state may further increase cerebrovascular events [6, 7]. The Centers for Disease Control (CDC) Vaccine Adverse Event Reporting System (VAERS) has announced several neurological complications following COVID-19 vaccines [8]. The most common neurological symptoms following COVID-19 vaccines have included headache, anosmia, dysgeusia, myalgia, paresthesia, weakness, and dizziness [9]. Several rare side effects, including tremor, diplopia, tinnitus, dysphonia, delirium, and syncope, have also been observed that are significant to note [10, 11]. The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell’s palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

Bells palsy

Bell’S palsy (BP), known as idiopathic facial paralysis, is an acute unilateral peripheral facial nerve palsy [12]. This condition is, in fact, an idiopathic facial palsy of spontaneous origin, although a causal association with the herpes simplex virus has been considered [13]. However, in the current pandemic, studies revealed abundant cases of BP following SARS-CoV-2 infection [1416]. Several vaccines, including influenza, hepatitis B, and meningococcal conjugate vaccines, have been associated with BP [1719]. With the development of COVID-19 vaccines, significant concerns have arisen about their potential to trigger the onset of Bell’s palsy. Despite being less prevalent than expected, this complication has still been abundantly reported following these vaccines [12, 20, 21]. Nonetheless, the US Food and Drug Administration (FDA) announced that the frequency of Bell’s palsy cases following vaccination is not more unusual than in the general population [22]. Despite the inability to confirm the causal relationship between the vaccines and this complication, the timing of onset following vaccination can suggest the association. Confirmation would need to be studied in larger populations [23]. This reaction could be either immune-mediated or induced by viral reactivation [24], but the latter does not seem valid for COVID-19 vaccines since no live attenuated COVID-19 vaccine platform has yet been introduced.

The immune-mediated mechanism for this complication is thought to be through host molecules’ mimicry of the vaccine’s antigens or by eliciting a type I interferons response [25, 26]. The timing of BP onset in relationship to vaccination is unclear, although most of the cases have occurred in an average 4-week interval after vaccination [27]. Moreover, there has been a case of sequential contralateral facial nerve palsies following each dose of COVID-19 vaccines reported recently [27]. Up to now, BP has been reported following various COVID-19 vaccine types, including Pfizer-BioNTech, Janssen, CoronaVac, Moderna, and Oxford-AstraZeneca vaccines [12, 23, 2830]. Nonetheless, the risk of developing facial nerve palsy has been estimated to be higher with mRNA vaccines than with other vaccine platforms; this fact can help us decide the choice of COVID-19 vaccine in individuals with a history of BP [31]. It is vital to note that most cases of BP, regardless of etiology, are self-limiting and subside within a few months [32]. However, antiviral agents and steroids are frequently tried as a treatment and hasten recovery [32].

Guillain–Barré Syndrome

Guillain–Barré Syndrome (GBS) is defined as an inflammatory ascending polyradiculoneuropathy. The underlying triggers for this neurological disorder include infections and vaccines on an autoimmune basis [33] (Fig. 1). The introduction of COVID vaccines has arisen the concerns of developing GBS following vaccination [34] since GBS had been previously observed in individuals who received the meningococcal, tetanus-toxoid, human papillomavirus (HPV), and most prominently, the influenza vaccines [3539]. This complication has been reported following Pfizer-BioNTech, Johnson & Johnson, and ChAdOx1 nCoV-19 COVID-19 vaccines [1, 4042]. Moreover, one case of isolated bilateral facial diplegia with paresthesias (BFP), an uncommon variant of GBS, has been reported following the Janssen COVID-19 vaccination [43]. It is believed that vaccine-induced immune responses may trigger autoimmune reactions, resulting in autoantibody production against myelin, resulting in GBS [40]. The diagnosis of vaccine-induced GBS is the same as that of other causes, through clinical and paraclinical findings such as cerebrospinal fluid (CSF) analysis and electromyography and nerve conduction velocity (EMG/NCV) studies, in addition to considering the temporal relationship between the event and vaccination [44]. Intravenous immune globulin (IVIg) (0.4 g per kg body weight every day for 5 days) and plasma exchange (200–250 ml plasma kg body weight in 5 sessions) can be considered as efficient treatments for GBS [45].

Fig. 1.

Fig. 1

COVID-19 vaccine-induced Guillain–Barré syndrome. After the administration of the COVID-19 vaccine, the vaccine particles enter the body and activate APCs, which could trigger B cells and CD4+ T cells activation. Naïve CD4+ T cells are then differentiated into three subgroups, Th1, Th2, and Th17, producing cytokines, such as IL-2, IL-4, IL-10, IL-12, IL-17A, TNF-α, and IFY-γ. Moreover, B cells are converted to plasma cells, secreting antiganglioside antibodies. These antibodies are then gone through the blood-nerve barrier, binding to the ganglioside of the myelinated motor neurons or attaching to the neuromuscular junction. As a result of forming gangliosides-antiganglioside antibody complexes, MAC and macrophages are activated, attacking and destroying the myelin. Such demyelination would decrease the speed of action potential transmission through these nerves, causing an inflammatory ascending polyradiculoneuropathy. IVIg administration could reverse these mechanisms via 2 main pathways: triggering Treg cells, inhibiting B cells and inflammatory cytokines, and dimerizing with antiganglioside antibodies. Moreover, plasmapheresis could alleviate the symptoms via actively depleting inflammatory cytokines from patients’ bloodstream. Furthermore, cysteine proteases can degrade antiganglioside antibodies, inhibiting this inflammatory neuropathy. Eculizumab and nafamostat mesylate would also inhibit MAC, alleviating the demyelination. Abbreviations: APC Antigen-presenting cell, TCR T cell receptor, MHC II Major histocompatibility complex II, BCR B cell receptor, Th T helper cell, IL-2 Interleukin-2, IL-4 Interleukin-4, IL-10 Interleukin-10, IL-12 Interleukin-12, IL-17A Interleukin-17A, TNF-α Tumor necrosis factor-α, IFY-γ Interferon-γ, GBS Guillain-Barré syndrome, IVIg Intravenous immune globulin, Treg regulatory T cell, TGF-β Transforming growth factor-β, PP Plasmapheresis, IFN-β Interferon-β, MAC Membrane attack complex

Transverse myelitis

Transverse myelitis (TM) is a condition where spinal cord segments may become inflamed, resulting in significant motor, autonomic and sensory deficits. [46]. Since the beginning of the current pandemic, several cases of TM have been reported in SARS-CoV-2-infected patients [47, 48]. Apart from infections as a cause of TM, vaccines are of great importance in the evolution of this neurological condition [49]. TM following vaccination had previously been observed with various vaccines, including tetanus, measles–mumps–rubella, influenza (H1N1), hepatitis B, polio, and Japanese B encephalitis vaccines [5054]. This neurological complication has also been reported following COVID-19 vaccination with viral vector-based and mRNA-based COVID-19 vaccines. However, their association has not been confirmed in a number of trials [2, 5557]. Moreover, a rare subtype of TM, known as longitudinally extensive transverse myelitis (LETM), has been reported following COVID-19 vaccination [58]. The pathophysiology of TM in the settings of SARS-CoV-2 infection is thought to be either via direct viral neuro-invasion or immune-mediated, while the mechanism by which COVID-19 vaccines might trigger TM may be immune and inflammatory reactions [59, 60]. The diagnosis is made by typical clinical evidence of bilateral sensory, motor, or autonomic dysfunction with an established spinal cord defect origin in magnetic resonance imaging (MRI) [61]. Unfortunately, TM is a neurological condition with unfavorable outcomes [62]. Although there is insufficient evidence, high-dose IV methylprednisolone (1 g per day for 3–7 days) has to be started immediately for all TM cases to improve neurological function and accelerate recovery [63, 64]. In a case report study, a COVID-19 patient with acute TM treated with high-dose IV methylprednisolone (1 g daily for 3 days) showed improved neurological symptoms immediately after receiving IV corticosteroid therapy [65].

Cerebrovascular events

Since the beginning of the COVID-19 pandemic, a significant increase in stroke rates was observed, later discovered to be due to SARS-CoV-2 infection [6668]. Although not as common as SARS-CoV-2 infection, COVID-19 vaccination is also suspected to increase the risk of cerebrovascular events [69]. It is unknown whether the cerebrovascular events, including ischemic/hemorrhagic strokes and cerebral venous sinus thrombosis, are related to COVID-19 vaccination. If they are related, it also remains unclear how the vaccines may contribute–by causing arterial hypertension, worsening thrombocytopenia, or exacerbating a hypercoagulable state [70, 71]. Previously, a stroke took place following vaccination with various other vaccines, including diphtheria, measles–mumps–rubella, and influenza vaccines [7274]. The probability and reports of systemic thrombotic thrombocytopenic events following COVID-19 vaccination have caused a great deal of concern and hesitancy worldwide [71]. The Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine had been the most notorious for this complication that many countries suspended its use [75]. However, thrombotic events have not been uncommon following the Johnson & Johnson COVID-19 vaccine [76, 77]. Cerebrovascular events, including hemorrhagic and ischemic strokes, from venous and arterial etiologies and an increased thrombotic and embolic risk, have been noted [7881]. There have been reports of thrombosis in the cortical veins, transverse sinus, sigmoid sinus, inferior sagittal sinus, the vein of Galen, and the straight sinus that have all presented with intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH), shortly after COVID-19 vaccination [8083].

However, we should take into account that individuals with risk factors of thromboembolic events, such as pregnancy, postpartum state, oral contraceptives use, surgery, trauma, immobilization, malignancies, and thrombophilic genetic or autoimmune conditions including anti-thrombin, protein C, and protein S deficiency, factor V Leiden mutation, antiphospholipid antibodies, and hyperhomocysteinemia, are more prone to vaccine-induced cerebrovascular complications [8487]. It is important to note that anti-CXCL4 antibodies are responsible for most cases of vaccine‐induced immune thrombotic thrombocytopenia (VITT); this is similar to what happens with heparin-induced thrombocytopenia (HIT) [71, 88]. Depending on which vessel is involved, clinical manifestations may range from a simple headache, nausea, vomiting, and diplopia to focal neurologic signs, altered consciousness, and coma. The diagnosis of cerebrovascular AEs is generally made with comprehensive imaging, including brain computed tomography (CT), venogram, angiography, and MRI [89]. Management of cerebrovascular events following vaccination is generally the same as with any other cause, with the goal being assessment and management of risk factors and secondary stroke prevention. Heparin and platelet transfusions should be avoided until VITT has been excluded [90, 91]. In cases of systemic thrombotic thrombocytopenic events, IVIg, high-dose glucocorticoids, and plasmapheresis are recommended when indicated to restore platelet counts and address the autoimmune phenomenon [79, 92].

Encephalopathy

Acute encephalopathy has been attributed to various etiologies, including toxins, infections, and vaccines. One of the most prevalent neurological sequelae of COVID-19 has been encephalopathy which presents with cognitive impairment, altered consciousness, and even seizures [9396]. However, the condition has been observed much less frequently following COVID-19 vaccination [94, 97100]. In the past, several cases of encephalopathy had been reported after various vaccines, including hepatitis B, rabies, pertussis, measles, influenza, and HPV vaccines [101107]. The pathophysiologic mechanism for vaccine-induced acute disseminated encephalomyelitis (ADEM) seems to be the inflammatory cascade or the cytokine storm triggered by the production of spike protein from translated mRNA in the vaccines [108, 109]. The diagnosis of ADEM in the settings of COVID-19 vaccination is similar to that of other causes and is accomplished through clinical and cerebrospinal fluid (CSF) findings and imaging modalities such as brain MRI. The treatment consists of corticosteroids and sometimes IVIg and plasmapheresis [110]. Fortunately, ADEM has a favorable outcome if conservative support is satisfactory [111].

New-onset seizures

The pathophysiologic mechanisms of seizures during a SARS-CoV-2 infection differ significantly from those following COVID-19 vaccination. In the former, specific antibiotic therapies, cerebral hypoxemia, acute renal failure, and electrolyte impairment can be the underlying reasons [112114]. The latter can happen in the settings of vaccine-induced encephalopathy or venous occlusion [97]. Before the current pandemic, HPV and H1N1 vaccinations had been related to functional (non-epileptic) seizures, which were believed to be psychogenic attacks [115, 116]. The association of febrile seizure with the measles–mumps–rubella–varicella vaccine has long been well established [117]. It is unknown whether non-motor seizures are related to COVID-19 vaccines or only a coincidence [118]. Patients with a known history of epilepsy or prior history of seizures may have a decreased threshold in the post-vaccine period due to the symptoms and illness. Rare attacks have included new-onset refractory status epilepticus that require further assessment and follow-up [119]. The diagnosis is based on clinical history, physical examinations, brain imaging (CT scan and MRI), electroencephalography, and serum prolactin level measurement. There are a variety of antiepileptic drugs (Table 1) that can be administered as first-line monotherapy in adults with epilepsy [120].

Table 1.

Summary of the proposed diagnosis and management of neurological adverse events following COVID-19 vaccination 

Neurological adverse event Diagnosis Management
Bell’s palsy History and physical examination: Rapid-onset (less than 72 h) unilateral paralysis of the facial nerve (weakness or complete loss of movement) with no defined reason Oral corticosteroids (prednisolone) and antiviral agents (acyclovir and valacyclovir)
Guillain–Barré Syndrome Clinical and paraclinical findings such as cerebrospinal fluid (CSF) analysis and electromyography and nerve conduction velocity (EMG/NCV) studies, in addition to considering the temporal relationship between the event and vaccination IVIg (0.4 g per kg body weight every day for 5 days) and plasma exchange (200–250 mL plasma per kg body weight in 5 sessions) are similarly efficient remedies for GBS
Transverse myelitis Typical clinical evidence of bilateral sensory, motor, or autonomic dysfunction with an established spinal cord defect origin in magnetic resonance imaging (MRI) High-dose IV methylprednisolone (1 g daily for 3–7 days)
Cerebrovascular events Brain computed tomography (CT), venogram, angiography, and MRI

IVIg

High-dose glucocorticoids

Plasmapheresis

Non-heparin anticoagulants (like fondaparinux and argatroban)

Encephalopathy Clinical and cerebrospinal fluid (CSF) findings and imaging modalities such as brain MRI Corticosteroids and sometimes IVIg and plasmapheresis
New-onset seizures Clinical history, physical examinations, brain imaging (CT scan and MRI), electroencephalography, and serum prolactin level measurement

Narrow-spectrum drugs (focal seizure) Carbamazepine

Eslicarbazepine

Gabapentin

Lacosamide

Oxcarbazepine

Phenytoin

Broad-spectrum drugs (focal and almost all generalized seizures)

Lamotrigine

Levetiracetam

Topiramate

Valproate

Zonisamide

Myasthenia gravis exacerbation Suspected through compatible signs and symptoms of fatigable muscle weakness and confirmed by EMG studies, pharmacologic testing, and serum Ab assay

Pyridostigmine (30 mg 3–4 times a day, then can be increased to 60 mg 4 times a day)

Oral prednisone (0.75–1 mg per kg daily)

Azathioprine

Cyclosporine

Tacrolimus

Rituximab

Varicella-zoster virus reactivation Clinical manifestations (dermatomal rash, pain, paresthesia, dysesthesia, allodynia, pruritus), IF test for VZV antigen, PCR test for VZV DNA

Acyclovir (800 mg orally 5 times a day for 7–10 days)

Valacyclovir (1 g orally 3 times a day for 7 days)

Famciclovir (500 mg orally 3 times a day for 7 days)

Varicella-zoster virus reactivation

Since the beginning of the COVID-19 pandemic, several cases of herpes zoster have been reported in SARS-CoV-2 infected patients, even in immunocompetent individuals [121, 122]. The potential mechanism for this event is suggested to be COVID-19-induced lymphopenia and CD4+ T cell dysfunction [123]. Nonetheless, immunomodulation, immune dysregulation, and attenuated alloreactivity are believed to be the underlying pathophysiology for vaccine-induced herpes zoster reactivation [124, 125]. Herpes zoster reactivation was previously reported following yellow fever, influenza, hepatitis A, and rabies vaccines [126, 127]. Up to the present time, this neurological complication has been reported following various COVID-19 vaccines, including mRNA-based (Pfizer-BioNTech, Moderna), viral vector (Oxford ChAdOx1-S or AZD1222), and inactivated vaccines (COVAXIN) [125, 128133]. Moreover, a case of varicella-zoster virus-induced small vessel vasculitis following the first dose of the Pfizer-BioNTech COVID-19 vaccine has been reported [134]. It should be noted that in all suspected cases of vaccine-induced herpes zoster reactivation, a de novo SARS-CoV-2 infection should be ruled out. The diagnosis is made with clinical manifestations (dermatomal rash, pain, paresthesia, dysesthesia, allodynia, and pruritus), immunofluorescence (IF) test for VZV antigen, and PCR test for VZV DNA. acyclovir, valacyclovir, and famciclovir (guanosine analogs) are recommended for VZV treatment [135].

Miscellaneous neurological adverse events

Apart from the aforementioned neurological side effects, some other AEs, including narcolepsy, small fiber neuropathy, neuroleptic malignant syndrome (NMS), and multiple sclerosis flare-ups, have been reported following COVID-19 vaccination, although their causal relationships are not confirmed [4, 136139].

Relative risks of neurological adverse events in SARS-CoV-2 infection vs. post-COVID-19 vaccination

Many studies have reported various neurological disorders associated with COVID-19 infection and vaccines [80, 140143]. However, given the shortage of comprehensive, prospective studies, it is still far too difficult to establish cause-effect relations between these factors. Therefore, future studies should determine the real risk of these adverse events following COVID-19 vaccination. Until then, it does not seem reasonable to limit vaccine administration. Nonetheless, considering the existing data, in this section, we have summarized some studies reporting cases of neurological adverse events associated with SARS-CoV-2 infection or vaccination (Table 2).

Table 2.

Summary of the reported cases of neurological adverse events following SARS-CoV-2 infection vs post-COVID-19 vaccination

Case number Reference Neurological disorder Sex/Age (years) Country Clinical manifestation Diagnosis Treatment Associated with SARS-CoV-2 infection vs post-COVID-19 vaccination
1 Afshar et al. [144]/2021 Bell’s palsy F/64 Iran Left side facial nerve palsy

History and physical examination,

brain CT scan and MRI, pulmonary CT scan, RT-PCR for SARS-CoV-2, and anti-SARS-CoV-2 IgM test

lopinavir/ritonavir (Kaletra) + dexamethasone Associated with COVID-19 infection
2 Dahl et al. [145]/2021 Bell’s palsy M/37 Norway Right side facial nerve palsy

History and physical examination,

cerebral CT scan, spinal fluid examination, spinal fluid PCR, anti-SARS-CoV-2 IgG antibodies test

Associated with COVID-19 infection
3 Bastola et al.[146]/2021 Bell’s palsy M/48 India Left side facial nerve palsy

History and physical examination,

chest HRCT and PCR for SARS-CoV-2

Prednisolone Associated with COVID-19 infection
4 Al-Mashdali et al.[147]/2021 Bell’s palsy M/21 Qatar Right side facial nerve palsy

History and physical examination,

chest CT scan and RT-PCR for SARS-CoV-2

Prednisolone and eye lubricant Associated with COVID-19 infection
5 Hasibi et al.[148]/2021 Bell’s palsy M/52 Iran Right side facial nerve palsy

History and physical examination,

RT-PCR for SARS-CoV-2 and spiral chest CT scan

Prednisolone and favipiravir

Then: remdesivir and IV dexamethasone

Associated with COVID-19 infection
6 Ferreira et al.[149]/2022 Bell’s palsy M/11 Portugal Right side peripheral facial paralysis

History and physical examination,

PCR for SARS-CoV-2, cranial CT, and MRI

Prednisolone Associated with COVID-19 infection
7 Iacono et al.[150]/2022 Bell’s palsy M/5 Italy Right side facial nerve palsy

History and physical examination,

brain MRI and serological tests for SARS-CoV-2

Prednisolone and eye lubricant Associated with COVID-19 infection
8 Kaplan[151]/2021 Bell’s palsy F/48 USA Left side facial nerve palsy

History and physical examination,

PCR for SARS-CoV-2 and chest CT scan

Prednisone, valacyclovir, and doxycycline (the doxycycline was discontinued after Lyme disease titers became negative) Associated with COVID-19 infection
9 Szewczyk et al. [152]/2021 Bilateral facial nerve palsy M/70 Poland Bilateral facial nerve palsy

History and physical examination,

brain CT scan and MRI and serological tests for SARS-CoV-2

Intravenous immunoglobulins (IVIg) Associated with COVID-19 infection
10 Kumar et al. [153]/2021 Bell’s palsy F/28 India Right side lower motor neuron facial nerve palsy

History and physical examination,

RT-PCR for SARS-CoV-2

Prednisone and valacyclovir Associated with COVID-19 infection
11 Neo et al. [154]/2021 Bell’s palsy M/25 Singapore Left side facial weakness/palsy History and physical examination, RT-PCR for SARS-CoV-2, and serological tests for SARS-CoV-2 Oral corticosteroids, valacyclovir, and eye care advice Associated with COVID-19 infection
12 Neo et al. [154]/2021 Bell’s palsy M/34 Singapore Right side facial weakness History and physical examination, RT-PCR for SARS-CoV-2, and serological tests for SARS-CoV-2 Oral corticosteroids, valacyclovir, and eye care advice Associated with COVID-19 infection
13 Khaja et al. [155]/2020 Guillain-Barré Syndrome and Bell’s Palsy M,44 USA Bilateral facial weakness History and physical examination, RT-PCR for SARS-CoV-2, serological tests for SARS-CoV-2, and brain MRI IVIg Associated with COVID-19 infection
14 Theophanous et al. [156]/2021 Bell’s palsy M/6 USA Right side facial nerve palsy History and physical examination, RT-PCR for SARS-CoV-2

IV acyclovir and IVIg infusion (because of agammaglobulinemia)

Then discharged with prednisolone and acyclovir

Associated with COVID-19 infection
15 Wan et al. [157]/2020 Bell’s palsy F/65 China Left side facial nerve palsy History and physical examination, RT-PCR for SARS-CoV-2, and brain MRI Arbidol and ribavirin Associated with COVID-19 infection
16 Bohania et al. [158]/2021 Bell’s palsy F/18 Right side facial nerve palsy History and physical examination, COVID-19 antigen testing Steroids, eye taping during sleep, and methylcellulose eye drops Associated with COVID-19 infection
17 Burrows et al. [159]/2021 Bell’s palsy M/61 UK Right side lower motor neuron facial palsy History and physical examination and head CT scan Prednisolone Associated with COVID-19 vaccination (Pfizer-BioNTech)
18 Cellina et al. [160]/2022 Bell’s palsy F/35 Italy Left side facial nerve palsy History and physical examination and brain MRI Prednisone Associated with COVID-19 vaccination (Moderna)
19 Iftikhar et al .[12]/2021 Bell’s palsy M/36 Qatar Left side facial nerve palsy + left upper limb numbness and weakness History and physical examination, brain CT scan, and MRI Prednisolone and eye lubricant Associated with COVID-19 vaccination (Moderna)
20 Mussatto et al. [161]/2022 Bell’s palsy (he was also a 20-year-prior case of HIV) M/60 USA Left side facial nerve palsy History and physical examination Prednisone and valacyclovir Associated with COVID-19 vaccination (Pfizer-BioNTech)
21 Repajic et al. [28]/2021 Bell’s palsy F/57 USA Left side facial nerve palsy History and physical examination Prednisone and an antiviral agent Associated with COVID-19 vaccination (Pfizer-BioNTech)
22 Yu et al. [162]/2021 Bell’s palsy F/36 China Right side facial nerve palsy History and physical examination, serological tests for SARS-CoV-2, and brain CT scan Prednisone and artificial tear Associated with COVID-19 vaccination (Sinovac Life Sciences inactivated COVID-19 vaccine)
23 Mason et al. [163]/2021 Bell’s palsy F/35 USA Bilateral facial nerve palsy History and physical examination, brain MRI and CT angiography Methylprednisolone (IV) and acyclovir Associated with COVID-19 vaccination (Moderna)
24 Mirmosayyeb et al. [164]/2022 Bell’s palsy F/27 Iran Left side facial nerve palsy History and physical examination and brain MRI Prednisone and valacyclovir Associated with COVID-19 vaccination (Russian Sputnik V)
25 Mirmosayyeb et al. [164]/2022 Bell’s palsy M/58 Iran Left side facial nerve palsy History and physical examination Prednisone and valacyclovir Associated with COVID-19 vaccination (Russian Sputnik V)
26 Pothiawala[165]/ 2021 Bell’s palsy M/46 Singapore Right side facial nerve palsy History and physical examination Prednisone and acyclovir Associated with COVID-19 vaccination (Moderna)
27 Kundi et al.[166]/2022 Bell’s palsy F/66 USA Right side facial nerve palsy History and physical examination and brain CT Prednisone, acyclovir, meclizine, and ondansetron Associated with COVID-19 vaccination (Ad26.COV2.S vaccine)
28 Nishizawa et al. [167]/2021 Bell’s palsy F/62 Japan Right side facial nerve palsy History and physical examination, head CT and brain MRI Associated with COVID-19 vaccination (Ad26.COV2.S vaccine)
29 Colella et al. [20]/2021 Bell’s palsy M/37 Italy Left side facial nerve palsy History and physical examination Prednisone and artificial tear Associated with COVID-19 vaccination (Pfizer-BioNTech)
30 Martin-Villares et al. [168]/2022 Bell’s palsy F/34 Spain Right side facial nerve palsy History and physical examination and brain MRI Associated with COVID-19 vaccination (Moderna)
31 Scheidl et al. [169]/2020 Guillain-Barré Syndrome F/54 Germany Acute, proximally pronounced, moderate, symmetric paraparesis, areflexia, numbness, and tingling of all extremities RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
32 Bueso et al. [170]/2021 Guillain-Barré Syndrome F/60 USA Symmetrical weakness of both the lower and upper extremities RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis) IVIg (0.4 g per kg body weight every day for 5 days) + enoxaparin 30 mg twice a day Associated with COVID-19 infection
33 Sedaghat and Karimi [171]/2020 Guillain-Barré Syndrome M/65 Iran Acute progressive weakness of distal lower extremities, quadriplegia, and bilateral facial paresis RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
34 Agosti et al. [172]/2021 Guillain-Barré Syndrome M/68 Italy Acute progressive symmetric ascending flaccid tetraparesis, bifacial nerve palsy, and muscular weakness RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
35 Paybast et al. [173]/2020 Guillain–Barré Syndrome M/38 Iran Acute symmetric progressive ascending paresthesia of both lower and upper extremities and bilateral facial droop clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) Therapeutic plasma exchange for 5 sessions Associated with COVID-19 infection
36 Paybast et al. [173]/2020 Guillain-Barré Syndrome F/14 Iran Progressive ascending quadripareshtesia and mild lower limb weakness Clinical and paraclinical findings (such as CSF analysis) IVIg (20 g daily for 5 d) Associated with COVID-19 infection
37 Dufour et al. [174]/2021 Guillain-Barré Syndrome F/36 USA Progressive ascending weakness RT-PCR for SARS-CoV-2, history and physical examinations IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
38 Toscano et al. [175]/2020 Guillain-Barré Syndrome Italy Flaccid areflexic tetraplegia evolving to facial weakness, upper-limb paresthesia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and head and spine MRI) 2 IVIg cycles Associated with COVID-19 infection
39 Toscano et al. [175]/2020 Guillain-Barré Syndrome Italy Facial diplegia and generalized areflexia evolving to paresthesia of lower limbs with ataxia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and head and spine MRI) IVIg Associated with COVID-19 infection
40 Toscano et al. [175]/2020 Guillain-Barré Syndrome Italy Flaccid tetraparesis and facial weakness evolving to areflexia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and head and spine MRI) 2 IVIg cycles Associated with COVID-19 infection
41 Toscano et al. [175]/2020 Guillain-Barré Syndrome Italy Flaccid areflexic tetraparesis and ataxia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and head and spine MRI) IVIg Associated with COVID-19 infection
42 Toscano et al. [175]/2020 Guillain-Barré Syndrome Italy Facial weakness, flaccid areflexic paraplegia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and head and spine MRI) IVIg and plasma exchange Associated with COVID-19 infection
43 El Otmani et al. [176]/2020 A subtype of GBS: Acute Motor and Sensory Axonal Neuropathy (AMSAN) F/70 Morocco Bilateral weakness and paresthesia in all four extremities RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) IVIg (2 g/kg for 5 days), Hydroxychloroquine (600 mg/day), and Azithromycin (500 mg on the first day, then 250 mg/day) Associated with COVID-19 infection
44 Khan et al. [177]/2021 Guillain-Barré Syndrome M/27 India Myalgia, weakness of the lower limb (then it involved the upper limb), and generalized hypotonia RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
45 Khan et al. [177]/2021 Guillain-Barré Syndrome F/35 India Paresthesia in both lower limbs followed by mild weakness COVID-19 testing (she was positive for COVID‐19), clinical and paraclinical findings (such as CSF analysis and NCV studies) Managed as a case of COVID‐19 (Supportive) Associated with COVID-19 infection
46 Khan et al. [177]/2021 Guillain-Barré Syndrome F/40 India Lower-limb paresthesia is associated with weakness rapidly progressing from lower to upper limbs, respiratory muscles weakness Clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
47 Khan et al. [177]/2021 Guillain-Barré Syndrome F/48 India Paresthesia in both lower limbs and weakness RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
48 Khan et al. [177]/2021 Guillain-Barré Syndrome M/50 India Paresthesia in both lower limbs (then it involved upper limbs) and weakness RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
49 Su et al. [178]/2020 Guillain-Barré Syndrome with dysautonomia M/72 USA Symmetric paresthesias and ascending appendicular weakness SARS-CoV-2 PCR, clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) IVIg (2 g/kg between days 3 and 6) Associated with COVID-19 infection
50 Darvishi et al. [179]/2021 Guillain-Barré Syndrome M/56 Iran Subacute progressive lower limbs weakness, paresthesia, and pain (then it progressed to severe, flaccid paraparesis) RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis) IVIg (0.5 g/kg/d for 5 days) Associated with COVID-19 infection
51 Zhao et al. [180]/ 2020 Guillain-Barré Syndrome F/61 China Symmetric weakness and areflexia in both lower limbs RT-PCR for SARS-CoV-2, clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg Associated with COVID-19 infection
52 Mackenzie et al. [181]/2021 Guillain-Barré Syndrome F/39 Colombia Progressive generalized weakness of lower limbs SARS-CoV-2 PCR, clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) Supportive care, enoxaparin, losartan, meperidine IV for muscle pain, hydroxychloroquine, and dexamethasone Associated with COVID-19 infection
53 Mostel et al. [182]/2021 Guillain-Barré Syndrome F/69 USA Progressive motor weakness and sensation loss in extremities, numbness and paresthesia in the right hand and leg, numbness and paresthesia in the left limb SARS-COV-2 antibodies, clinical and paraclinical findings (such as EMG studies) IVIg (2 g/kg for 5 days) Associated with COVID-19 infection
54 Farzi et al. [183]/2020 Guillain-Barré Syndrome M/41 Iran Ascending paresthesia and paralysis SARS-CoV-2 PCR, clinical and paraclinical findings (such as EMG and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 infection
55 Nejad et al. [184]/2021 Guillain-Barré Syndrome M/70 Iran Symmetric weakness and arefexia in both lower limbs SARS-CoV-2 PCR, clinical and paraclinical findings (such as CSF analysis) IVIg Associated with COVID-19 infection
56 McKean et al. [185]/ 2021 Guillain-Barré Syndrome M/48 Malta Bilateral facial weakness, ascending paraesthesia, and bilateral progressive lower limb weakness Clinical and paraclinical findings (such as CSF analysis and NCV studies),brain CT and MRI IVIg (2 g/kg for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
57 Hasan et al. [186]/2021 Guillain-Barré Syndrome F/62 UK Paraesthesia and progressive weakness of both lower limbs Clinical and paraclinical findings (such as CSF analysis and NCV studies),brain CT and MRI IVIg (2 g/kg for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
58 Allen et al. [187]/2021 Guillain–Barré Syndrome M/54 UK Bilateral facial weakness and distal dysesthesia in hands and feet Clinical and paraclinical findings (such as CSF analysis and NCV studies),brain MRI Oral prednisolone (60mg for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
59 Allen et al. [187]/2021 Guillain–Barré Syndrome M/20 UK Bilateral facial weakness and distal dysesthesia in feet Clinical and paraclinical findings (such as CSF analysis and NCV studies),brain MRI Oral prednisolone (60 mg for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
60 Allen et al. [187]/2021 Guillain-Barré Syndrome M/57 UK Dysarthria and facial weakness, distal dysesthesia in feet, and proximal leg weakness

Clinical and paraclinical findings (such as CSF analysis and NCV studies), and

brain MRI

IVIg Associated with COVID-19 vaccination (Oxford/AstraZeneca)
61 Allen et al. [187]/2021 Guillain–Barré Syndrome M/55 UK Bilateral thigh paresthesia, bilateral facial weakness Clinical and paraclinical findings (such as CSF analysis) and brain MRI No treatment Associated with COVID-19 vaccination (Oxford/AstraZeneca)
62 Min et al. [188]/2021 Sensory Guillain–Barré Syndrome M/58 Republic of Korea Severe paresthesia on both feet, mild hypoesthesia in vibration, temperature, and pain on both feet

SARS-CoV-2 PCR, Clinical and paraclinical findings (such as CSF analysis, NCV studies, and skin biopsy), and

MRI

Associated with COVID-19 vaccination (Oxford/AstraZeneca)
63 Min et al. [188]/2021 Sensory Guillain-Barré Syndrome F/37 Republic of Korea Paresthesia in both lower limbs

SARS-CoV-2 PCR, Clinical and paraclinical findings (such as CSF analysis, NCV studies, and skin biopsy), and

MRI

Associated with COVID-19 vaccination (Oxford/AstraZeneca)
64 Scendoni et al. [189]/2021 Guillain-Barré Syndrome F/82 Italy Progressively worsening of walking, weakness, lack of sensitivity in both lower limbs, and areflexia Clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies) IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 vaccination (Pfizer-BioNTech)
65 Maramattom et al. [190]/2021 Guillain–Barré Syndrome F/43 India Areflexic quadriparesis, facial diplegia, and respiratory failure Clinical and paraclinical findings (such as CSF analysis and NCV studies) IVIg Associated with COVID-19 vaccination (Oxford/AstraZeneca)
66 Maramattom et al. [190]/2021 Guillain-Barré Syndrome F/67 India Distal paraesthesia in all the extremities, bilateral facial weakness, dysphagia, and increasing limb weakness IVIg and plasmapheresis Associated with COVID-19 vaccination (Oxford/AstraZeneca)
67 Maramattom et al. [190]/2021 Guillain-Barré Syndrome F/53 India Bilateral lower limb numbness and weakness, right-sided facial and tongue numbness (then it progressed to bilateral lower motor neuron facial palsy and Areflexic flaccid quadriplegia) Mechanical ventilation Associated with COVID-19 vaccination (Oxford/AstraZeneca)
68 Introna et al. [191]/2021 Guillain-Barré Syndrome M/62 Italy Absent deep tendon reflexes, severe bilateral optic disk edema, progressively worsening sensory ataxia and ascending quadriparesis Clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies), brain CT and MRI IVIg (2 g/kg for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
69 Razok et al. [192]/2021 Guillain-Barré Syndrome M/73 Qatar Progressive bilateral lower limb weakness Clinical and paraclinical findings (such as CSF analysis and EMG and NCV studies), brain CT and MRI IVIg (0.4 g per kg body weight every day for 5 days) Associated with COVID-19 vaccination (Pfizer-BioNTech)
70 Rao et al. [193]/2021 Guillain-Barré Syndrome F/42 USA Progressive ascending weakness and paresthesias Clinical and paraclinical findings (such as CSF analysis and NCV studies), brain and cervical MRI IVIg (total of 2 g/kg in four divided doses) Associated with COVID-19 vaccination (Pfizer-BioNTech)
71 Moreno-Escobar et al. [194] Transverse myelitis M/41 Bilateral paresthesia in upper and lower limbs, along with urinary and fecal retention Serological study and CSF analysis, imaging studies IV methylprednisolone Associated with COVID-19 infection
72 Qazi et al. [195]/2021 Transverse myelitis F/35 Pakistan Abrupt bilateral lower limb weakness, paresthesia, and urinary retention Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 7 days) Associated with COVID-19 infection
73 Chow et al. [196]/2020 Transverse myelitis M/60 Australia Bilateral lower limb weakness, urinary retention, and constipation Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 3 days) Associated with COVID-19 infection
74 Sarma et al.[197]/2020 Transverse myelitis F/28 USA Lower back pain, bilateral symmetric upper and lower extremity numbness, and urinary retention Serological study and CSF analysis, imaging studies Prednisolone and plasma exchange Associated with COVID-19 infection
75 Ahmad et al. [198]/2021 Transverse myelitis F/34 Iraq Progressive intermittent leg pain, paresthesia, and weakness on both sides Serological study and CSF analysis, imaging studies IV methylprednisolone (500 mg 1 × 1 for 5 days) Associated with COVID-19 infection
76 Nejad Biglari et al.[199]/2021 Transverse myelitis F/11 Iran Acute paresis in the lower limbs, urinary and fecal retention Serological study and CSF analysis, imaging studies IVIg (0.4 g per kg body weight every day for 5 days) + pulse of methylprednisolone 30 mg/ Kg for 3 days Associated with COVID-19 infection
77 Palahuta et al. [200]/2021 Transverse myelitis M/23 Ukraine Acute-onset non-compressive myelitis with bilateral paresthesia Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 5 days) Associated with COVID-19 infection
78 Lingas [201]/2022 Transverse myelitis M/70 USA Numbness on both lower limbs Serological study and CSF analysis, imaging studies IV methylprednisolone (high dose), IVIg, ceftriaxone, ampicillin, and acyclovir Associated with COVID-19 infection
79 Prete [202]/2022 Transverse myelitis F/43 USA Progressive numbness and tingling in lower limbs and complete quadriplegia Serological study and CSF analysis, imaging studies Long-term steroid regimen and plasmapheresis Associated with COVID-19 infection
80 Shahali [203]/2021 Transverse myelitis M/63 Iran Weakness and immobility in lower extremities, constipation, and urinary retention Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 3 days) Associated with COVID-19 infection
81 Hsiao et al. [204] /2021 Transverse myelitis M/41 Taiwan Progressive paresthesia below T4, lower-limb weakness Serological study and CSF analysis, imaging studies IV methylprednisolone (1000 mg/day for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
82 Tan et al. [205]/ 2021 Transverse myelitis F/25 Malaysia Bilateral lower-limb weakness and impaired walking Serological study and CSF analysis, imaging studies IV methylprednisolone (1000 mg/day for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
83 Notghi et al. [206]/2021 Transverse myelitis M/58 UK Progressive numbness in lower limbs, allodynia up to chest level, genital dysaesthesia, and an episode of urinary incontinence Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
84 Pagenkopf et al. [58]/2021 Transverse myelitis M/45 Germany Acute flaccid tetraparesis (especially in the lower limbs) and urinary retention Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 5 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
85 Eom et al. [207]/ 2022 Transverse myelitis M/81 Republic of Korea Bilateral hand weakness and numbness Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 5 days) Associated with COVID-19 vaccination (Pfizer-BioNTech)
86 Eom et al. [207]/2022 Transverse myelitis F/23 Republic of Korea Bilateral paresthesia and weakness in the lower limbs Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 5 days) Associated with COVID-19 vaccination (Pfizer-BioNTech)
87 Miyaue et al. [208]/2022 Transverse myelitis M/75 Japan Total sensory loss below the umbilicus and complete paralysis in both lower limbs Serological study and CSF analysis, imaging studies IV methylprednisolone (1 g/day for 3 days), then oral prednisolone (initial dose of 1 mg/kg/day) Associated with COVID-19 vaccination (Pfizer-BioNTech)
88 Maroufi et al. [209]/2022 Transverse myelitis F/31 Iran Progressive lower limbs paraparesis and paresthesia, urinary retention, and fecal incontinence Serological study and CSF analysis, imaging studies

IV methylprednisolone (1 g/day for 7 days);

Then, oral prednisolone 50 mg daily

Associated with COVID-19 vaccination (Oxford/AstraZeneca)
89 Tahir et al. [210]/2021 Transverse myelitis F/44 USA Numbness and weakness in the lower extremities, urinary retention, and back pain Serological study and CSF analysis, imaging studies IV methylprednisolone and plasma exchange Associated with COVID-19 vaccination (Johnson and Johnson COVID-19 vaccine)
90 Hirose et al. [211]/2021 Transverse myelitis M/70 Japan Progressive sensorimotor dysfunction of both lower limbs Serological study and CSF analysis, imaging studies IV methylprednisolone (1000 mg/day for 5 days); then oral prednisolone (30 mg/day with gradual tapering) Associated with COVID-19 vaccination (Moderna)
91 Rajae et al. [212]/2021 Cerebrovascular events (ischemic stroke) M/68 Morocco Left hemiparesis with dysarthria and left facial paralysis Serological study and imaging studies (brain CT scan and MRI) Thrombolysis Associated with COVID-19 infection
92 Avvantaggiato et al. [213]/2021 Cerebrovascular events (ischemic stroke) F/29 Italy Left hemiplegia, left-sided central facial palsy, dysarthria, facial drop, and complete paralysis of the ipsilateral upper and lower limbs Serological study and imaging studies (brain CT scan and MRI) Associated with COVID-19 infection
93 Bigliardi et al. [214]/2020 Cerebrovascular events (ischemic stroke) M/62 Italy Left hemiplegia, left hemianopsia, and forced right deviation of gaze Serological study and imaging studies (brain CT scan and chest CT angiography) anticoagulant (LMWH) Associated with COVID-19 infection
94 Zhai et al. [215]/2020 Cerebrovascular events (ischemic stroke) M/79 China Right limb weakness and non-fluent speech Serological study and imaging studies (brain CT scan) Clopidogrel (75 mg) and atorvastatin (20 mg) Associated with COVID-19 infection
95 Farooque et al. [216]/2020 Cerebrovascular events (ischemic stroke) M/70 Pakistan Right-sided weakness and sensory loss in both upper and lower limbs Serological study and imaging studies (brain CT scan and MRI) Aspirin. (150 mg twice a day), LMWH (0.6 ml twice a day), and IV dexamethasone (1cc twice a day) Associated with COVID-19 infection
96 Owolabi et al. [217]/2021 Cerebrovascular events (hemorrhagic stroke) M/59 Saudi Arabia Right-sided incoordination, weakness, facial deviation, and altered level of consciousness Serological study and imaging studies (brain CT scan) Hydroxychloroquine, dexamethasone, remdesivir, and antibiotics Associated with COVID-19 infection
97 Owolabi et al. [217]/2021 Cerebrovascular events (hemorrhagic stroke) M/51 Saudi Arabia Left-sided limb and facial weakness Serological study and imaging studies (brain CT scan) Hydroxychloroquine, dexamethasone, and antibiotics Associated with COVID-19 infection
98 Fraiman et al. [218]/2020 Cerebrovascular events (hemorrhagic stroke) F/38 Brazil Acute alteration in the level of consciousness Serological study and imaging studies (brain CT scan and MRI) Associated with COVID-19 infection
99 Flores et al. [219]/2020 Cerebrovascular events (hemorrhagic stroke) M/40 USA Pinpoint, minimally reactive pupils, withdrawal to painful stimuli in the right side of the body, left hemiparesis Serological study and imaging studies (brain CT scan and MRI) Associated with COVID-19 infection
100 Dakay et al. [220]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) M/17 USA Left-sided headaches and occasional emesis Serological study and imaging studies (MRI brain with MR venography) Anticoagulation Associated with COVID-19 infection
101 Dakay et al. [220]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) F/72 USA Dyspnea and generalized weakness Serological study and imaging studies (CT angiogram) Associated with COVID-19 infection
102 Dakay et al. [220]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) M/26 USA Acute left-sided hemiparesis followed by severe headache, nausea, and dizziness Serological study and imaging studies (MRI brain with MR venography, brain CT scan, cerebral angiography, and CT angiogram) Associated with COVID-19 infection
103 Anipindi et al. [221]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) M/66 USA Severe headaches, palpitations, dizziness, and diaphoresis Serological study and imaging studies (MRI and CT brain along with CT venogram) Rivaroxaban 20 mg (6 months) Associated with COVID-19 infection
104 Tu et al. [222]/2020 Cerebrovascular events (cerebral venous sinus thrombosis) M/ mid-thirties Singapore Generalized non-remitting headache Serological study and imaging studies (MRI and CT brain along with CT venogram and MR venogram) Dabigatran Associated with COVID-19 infection
105 Tu et al. [222]/2020 Cerebrovascular events (cerebral venous sinus thrombosis) M/the late thirties Singapore First-onset seizure (generalized tonic–clonic convulsion) Serological study and imaging studies (CT brain along with CT venogram) IV heparin, IV levetiracetam, and cobalamin replacement Associated with COVID-19 infection
106 Blauenfeldt et al. [78]/2021 Cerebrovascular events (ischemic stroke) F/60 Denmark Strong, persistent abdominal pain, headache Serological study and imaging studies (CT brain) Hemicraniectomy + postoperative dalteparin 5000 IU daily Associated with COVID-19 vaccination (Oxford/AstraZeneca)
107 Elaidouni et al. [223]/2022 Cerebrovascular events (ischemic stroke) M/36 Morocco Numbness in left hemibody, headaches (24 h after the vaccine injection), Serological study and imaging studies (CT brain, MRI brain, MRI angiography of supra-aortic trunks) Aspirin and Enoxaparin (100 UI/kg/12 h) Associated with COVID-19 vaccination (Sinopharm)
108 Kenda et al. [224]/ 2021 Cerebrovascular events (ischemic stroke) F/51 Slovenia Acute-onset global aphasia, right-sided hemiplegia, and hemianopsia Serological study and imaging studies (CT/MRI brain and CT angiography) Mechanical thrombectomy + high-dose IVIg (1 g/kg for 2 consecutive days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
109 Al-Mayhani et al. [225]/2021 Cerebrovascular events (ischemic stroke) F/35 UK Right temporal and periorbital headache Serological study and imaging studies (CT brain and CT angiography) Urgent decompressive hemicraniectomy, IVIg, plasmapheresis, and fondaparinux Associated with COVID-19 vaccination (Oxford/AstraZeneca)
110 Al-Mayhani et al. [225]/2021 Cerebrovascular events (ischemic stroke) F/37 UK Diffused headache, left visual field loss, confusion, and left arm weakness Serological study and imaging studies (diffusion-weighted MRI and CT angiography) IVIg, IV methylprednisolone, plasmapheresis, and fondaparinux Associated with COVID-19 vaccination (Oxford/AstraZeneca)
111 de Mélo Silva et al. [226]/2021 Cerebrovascular events (hemorrhagic stroke) F/57 Brazil Acute-onset sweating and paleness, followed by left-sided hemiparesis, vomiting, and somnolence Serological study and imaging studies (CT brain) Hematoma drainage, external ventricular drain, and decompressive craniectomy Associated with COVID-19 vaccination (Oxford/AstraZeneca)
112 Takeyama et al. [227]/2022 Cerebrovascular events (hemorrhagic stroke) F/48 Japan Gradually progressing left-sided hemiparesis Serological study and imaging studies (CT/MRI brain and CT angiography) Right frontotemporal craniotomy Associated with COVID-19 vaccination (Pfizer-BioNTech)
113 Dias et al. [228]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) F/47 Portugal The sudden left-sided motor deficit, papilledema, left visual extinction, right gaze deviation, and left hemiparesis Serological study and imaging studies (MRI brain, MRI venography) Acetazolamide and enoxaparin 60 mg twice a day (later changed to warfarin) Associated with COVID-19 vaccination (Pfizer-BioNTech)
114 Dias et al. [228]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) F/67 Portugal Sudden right-sided lower limb clonic movements, motor deficit, loss of consciousness, and headache Serological study and imaging studies (MRI brain) and Electroencephalography Levetiracetam (500 mg twice a day) and enoxaparin (80 mg twice a day); then switched to dabigatran (150 mg twice a day) Associated with COVID-19 vaccination (Pfizer-BioNTech)
115 Zakaria et al. [229]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) M/49 Malaysia A new-onset headache and giddiness Serological study and imaging studies (CT brain and CT cerebral venogram) Subcutaneous Clexane (1 mg/kg twice a day) and clopidogrel (75 mg) Associated with COVID-19 vaccination (Pfizer-BioNTech)
116 D'Agostino et al. [230]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) F/54 Italy Left-sided signs Serological study and imaging studies (CT/MRI brain and CT/MRI angiography) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
117 Atta et al. [231]/2021 Cerebrovascular events (cerebral venous sinus thrombosis) F/48 UK Right-sided headache, Serological study and imaging studies (CT cerebral venogram) Fondaparinux (7.5 mg), IVIg (1 g/kg) and dexamethasone (20 mg/day) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
118 Delorme et al. [232]/2020 Encephalopathy M/72 France Acute psychomotor agitation, cognitive and behavioral frontal lobe syndrome, upper limbs myoclonus, and cerebellar ataxia CSF analysis, electroencephalogram (EEG), brain MRI, and brain FDG-PET/CT imaging IVIg (2 g/kg) Associated with COVID-19 infection
119 Delorme et al. [232]/2020 Encephalopathy F/66 France Acute cognitive impairment, psychomotor slowing, cognitive and behavioral frontal lobe syndrome, and severe apraxia CSF analysis, EEG, brain MRI, and brain FDG-PET/CT imaging IVIg; then, due to persisting severe cognitive impairment, IV pulse corticosteroids (2 mg/kg/day 3 days then 1 g/day 3 days) started Associated with COVID-19 infection
120 Delorme et al. [232]/2020 Encephalopathy F/60 France Acute anxiety, depressed mood, akathisia, gait imbalance, psychomotor agitation, dysexecutive syndrome, and cerebellar ataxia CSF analysis, EEG, brain MRI, and brain FDG-PET/CT imaging Pulse corticosteroids (2 mg/kg/day 3 days) Associated with COVID-19 infection
122 Delorme et al. [232]/2020 Encephalopathy M/69 France Generalized convulsive status epilepticus, fever, fatigue, anosmia, and ageusia CSF analysis, EEG, brain MRI, and brain FDG-PET/CT imaging Pulse corticosteroids (1 g/day 5 days) Associated with COVID-19 infection
123 Lazraq et al. [233]/2021 Encephalopathy M/79 Morocco Mental confusion, sudden-onset dysarthria The serological study, CSF analysis, EEG, brain CT, MRI, and MR angiography Sodium valproate Associated with COVID-19 infection
124 Goodloe et al. [234]/2021 Encephalopathy M/52 USA Altered mental status, fever, and severe agitation The serological study, CSF analysis, EEG, brain CT, and MRI Vancomycin, ceftriaxone, azithromycin, acyclovir, and clevidipine Associated with COVID-19 infection
125 Teimouri-Jervekani et al. [235]/2021 Encephalopathy M/53 Iran Severe headache and bizarre behavior The serological study, brain CT and MRI Hydroxychloroquine (200 mg twice a day for 5 days) Associated with COVID-19 infection
126 Al-Mashdali et al. [236]/ 2021 Encephalopathy M/32 Qatar Acute confusion, disturbed memory, and auditory hallucination The serological study, CSF analysis, EEG, and brain MRI Methylprednisolone Associated with COVID-19 vaccination (Moderna)
127 Liu et al. [237]/2021 Encephalopathy F/86 USA Acute confusion with visual hallucinations and left frontal headache The serological study, CSF analysis, EEG, brain CT, and MRI Lorazepam, fosphenytoin, and discharged with levetiracetam Associated with COVID-19 vaccination (Moderna)
128 Liu et al. [237]/2021 Encephalopathy M/73 USA Cognitive deficits, hallucinations, and periods of unresponsiveness The serological study, CSF analysis, EEG, brain CT, and MRI Lorazepam and levetiracetam Associated with COVID-19 vaccination (Moderna)
129 Baldelli et al. [108]/2021 Encephalopathy M/77 Italy Confusion, agitation, and delirium The serological study, CSF analysis, EEG, brain CT, and MRI Oral prednisone (50 mg per day) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
130 Bensaidane et al. [238]/2022 Encephalopathy M/56 Canada Altered mental status The serological study, CSF analysis, EEG, brain CT angiography, and MRI High-dose IV methylprednisolone (1 g/day for 7 days) Associated with COVID-19 vaccination (Oxford/AstraZeneca)
131 Monti et al. [239]/2020 New-onset seizures M/50 Italy Acute onset of psychiatric symptoms (confabulations and delirious ideas), focal motor seizures, and impaired awareness The serological study, CSF analysis, EEG, brain MRI, and total-body CT and PET Diazepam, valproic acid, lacosamide, methylprednisolone, IVIg, plasma-exchange Associated with COVID-19 infection
132 Bhatta et al. [240]/2020 New-onset seizures M/11 USA Acute-onset seizure for 2 min The serological study, EEG, and brain CT Levetiracetam (500 mg twice a day) Associated with COVID-19 infection
133 Park et al. [241]/2021 New-onset seizures F/45 USA Focal to bilateral tonic–clonic seizure, loss of consciousness, and urinary incontinence The serological study, CSF analysis, EEG, brain MRI, and CT Oxcarbazepine (600 mg twice a day); then lacosamide (200 mg twice a day) Associated with COVID-19 infection
134 Dono et al. [242]/2021 New-onset seizuresa M/81 Italy Non-convulsive status epilepticus with coma The serological study, CSF analysis, EEG, brain MRI, and CT

Lorazepam (4 mg two IV boluses), levetiracetam (2000 mg IV),

methylprednisolone (1 g/daily IV for 5 days); then, oral prednisolone (60 mg/day for 10 days) and IVIg (160 g over 5 days)

Associated with COVID-19 infection
135 Cho et al. [243]/2022 New-onset seizures M/84 Korea Myoclonic seizures (Myoclonic status epilepticus) The serological study, EEG, brain Diffusion-weighted MRI

Sedative medication: Midazolam

Antiseizure medication:

Lorazepam and Levetiracetam

Associated with COVID-19 infection
136 Cho et al. [243]/2022 New-onset seizures M/45 Korea Focal to bilateral tonic–clonic seizures (2 times) Serological study and EEG Sedative medication: Remifentanil and Dexmedetomidine Antiseizure medication: Lorazepam and Levetiracetam Associated with COVID-19 infection
137 Cho et al. [243]/2022 New-onset seizures M/63 Korea Focal impaired aware seizures (several times) Serological study and EEG Sedative medication: Dexmedetomidine Antiseizure medication: Phenobarbital, Levetiracetam, Topiramate, and Perampanel Associated with COVID-19 infection
138 Cho et al. [243]/2022 New-onset seizures M/72 Korea Myoclonic seizure, generalized tonic–clonic seizures (several times) Serological study and EEG Sedative medication: Remifentanil and Dexmedetomidine Antiseizure medication: Levetiracetam and Topiramate Associated with COVID-19 infection
139 Cho et al. [243]/2022 New-onset seizures M/73 Korea Myoclonic seizures (several times) Serological study and EEG

Sedative medication: Remifentanil and Propofol

Antiseizure medication: Levetiracetam and Valproic acid

Associated with COVID-19 infection
140 Cho et al. [243]/2022 New-onset seizures F/39 Korea Generalized tonic–clonic seizures (3 times) The serological study, EEG, brain CT Sedative medication:—Antiseizure medication: Levetiracetam Associated with COVID-19 infection
141 Aladdin et al. [119]/2021 New-onset seizures F/42 Saudi Arabia Generalized tonic–clonic seizure The serological study, CSF analysis, EEG, and brain MRI Lorazepam, phenytoin, levetiracetam, and lacosamide Associated with COVID-19 vaccination (Oxford/AstraZeneca)
142 Bauman et al. [244] New-onset seizures M/56 USA New-onset refractory status epilepticus The serological study, CSF analysis, EEG, and brain MRI Corticosteroids, plasmapheresis, IVIg, rituximab, midazolam, propofol, ketamine, levetiracetam, lacosamide, phenobarbital, clobazam, zonisamide, oxcarbazepine, and perampanel Associated with COVID-19 vaccination (Pfizer-BioNTech)
143 Desai et al. [245]/2021 Varicella-zoster virus reactivation F/62 India Painful blisters and fluid-filled bubble-form rashes Serological studies Oral and topical Acyclovir Associated with COVID-19 infection
144 Saleh et al. [246]/2021 Varicella-zoster virus reactivation F/49 Egypt Unilateral fluid-filled vesicles and painful erythematous areas over the hard palate Serological studies Oral acyclovir, topical antiseptics, chlorhexidine, and paracetamol Associated with COVID-19 infection
145 Saati et al. [122]/2020 Varicella-zoster virus reactivation M/57 Saudi Arabia Fluid-filled bubble-form rashes and vesicles with surrounding erythematous areas over the right nipple Serological studies Famciclovir Associated with COVID-19 infection
146 Van Dam et al. [129]/2021 Varicella-zoster virus reactivation F/29 The Netherlands Painful multiple vesicles on the left side of the ox coccyges Clinically diagnosed Associated with COVID-19 vaccination (Pfizer-BioNTech)
147 Van Dam et al. [247]/2021 Varicella-zoster virus reactivation M/34 The Netherlands Swollen, painful inguinal lymph nodes and a rash on the right lower limb Serological studies and PCR tests over vesical fluid for VZV Valacyclovir Associated with COVID-19 vaccination (Pfizer-BioNTech)
148 Rodríguez-Jiménez et al. [248]/2021 Varicella-zoster virus reactivation M/58 Spain Asymptomatic herpes-form umbilicated vesicles and lymphadenopathy in the cervical area PCR Associated with COVID-19 vaccination (Pfizer-BioNTech)
149 Rodríguez-Jiménez et al. [248]/2021 Varicella-zoster virus reactivation F/47 Spain Herpes-form umbilicated vesicles and dysesthesia PCR Associated with COVID-19 vaccination (Pfizer-BioNTech)
150 Rodríguez-Jiménez et al. [248]/2021 Varicella-zoster virus reactivation M/39 Spain Painful herpes-form umbilicated vesicles Associated with COVID-19 vaccination (Pfizer-BioNTech)
151 Rodríguez-Jiménez et al. [248]/2021 Varicella-zoster virus reactivation F/56 Spain Herpes-form umbilicated vesicles PCR Associated with COVID-19 vaccination (Pfizer-BioNTech)
152 Rodríguez-Jiménez et al. [248]/2021 Varicella-zoster virus reactivation F/41 Spain Herpes-form umbilicated vesicles and dysesthesia Associated with COVID-19 vaccination (Pfizer-BioNTech)
153 Santovito et al. (249)/2021 Varicella-zoster virus reactivation M/27 USA Popular rashes over the left upper limb Associated with COVID-19 vaccination (Pfizer-BioNTech)

Conclusion

The present review can help healthcare workers and also the general population by emphasizing these points: any neurological symptom after COVID-19 vaccination can be potentially critical and needs to be cautiously evaluated; for any suspected adverse event following vaccination, we should initially exclude current or recent SARS-CoV-2 infection; and despite the current literature on serious complications imposed by COVID-19 vaccines, the benefits of vaccination outweigh the risks in ending the current pandemic since all of these complications can occur with the infection itself.

Acknowledgments

The authors would like to thank the clinical research development center of Imam Reza Hospital, Kermanshah University of Medical Sciences, for their kind support.

Authors’ Contributions

ZMA: Data collection and writing the manuscript. AS: Data collection and contributed substantial revisions to the manuscript’s content. AB: Data collection and writing the manuscript. AAK: Data collection and helped with manuscript writing. TTS: Contributed substantial revisions to the manuscript’s content. MATM: Data collection and helped with manuscript writing. ATP: Data collection and helped with manuscript writing. AM: Data collection and helped with manuscript writing. RH: Helped with manuscript writing and visualization. MB: Data collection, helped with manuscript writing, and contributed substantial revisions to the manuscript’s content. SE: Design of the research study and supervision.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Conflict of interest

Terence T. Sio reports that he provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc. and also as a member of the Advisory Board to Galera Therapeutics, which are not in any way associated with the content or disease site as presented in this manuscript. All other authors have no relevant financial interests to be declared.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Mohammad Barary, Email: m.barary@mubabol.ac.ir.

Soheil Ebrahimpour, Email: drsoheil1503@yahoo.com.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.


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