Guillain-Barré Syndrome in Association with COVID-19 Vaccination: A Systematic Review

doi:10.21203/rs.3.rs-1821109/v1

Download PDF

Systematic Review

Guillain-Barré Syndrome in Association with COVID-19 Vaccination: A Systematic Review

https://doi.org/10.21203/rs.3.rs-1821109/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Since the beginning of worldwide vaccination against coronavirus disease 2019 (COVID-19), studies have reported a possible association between vaccination and Guillain-Barré syndrome (GBS). In this regard, we conducted a systematic review assessing different demographic, clinical, and neurophysiological aspects of patients with GBS following immunization with COVID-19 vaccines. A comprehensive search of PubMed, Web of Science, Scopus, and Google Scholar was performed. Articles in English between January 2020 and November 2021 were included. Data on demographics, clinical characteristics, vaccines information, treatment approaches, and outcomes were extracted. The data of a total of 88 patients out of 41 studies was included. The mean age of patients was 58.7 ± 16.6 years and 55 cases (62.5%) were male. AstraZeneca was the most-reported vaccine associated with GBS with 52 cases (59.1%) followed by Pfizer with 20 cases (22.7%). GBS occurred after the first dose of vaccination in 70 cases (79.5%). The mean time interval between vaccination and symptom onset was 13.9 ± 7.4 days. Limb weakness (47.7%), sensory disturbance (38.6%), and facial weakness (27.3%) were the most common reported symptoms, respectively. Albuminocytologic dissociation was seen in 65% of patients who underwent lumbar puncture (n = 65). Acute inflammatory demyelinating polyradiculopathy was the most common GBS subtype, which was reported in 38 patients (43.2%). While one-fifth of patients underwent intubation (n = 17), a favorable outcome was achieved in the majority of subjects (n = 46, 63%). Overall, a small rise in GBS incidence, following various COVID-19 vaccines, was observed. Notably, 85% of affected individuals experienced at least a partial recovery.

Neurology

Vaccine Development

Immunology

Guillain-Barré syndrome

Vaccination

COVID-19

SARS-COV-2

Guillain-Barré syndrome (GBS) is an autoimmune disease. In the majority of cases, the individual is affected by an infection or other immunological stimulants that results in an aberrant autoimmune response. The aberrated immunologic response targets the peripheral nerves and their spinal roots leading to a progressive neuropathic weakness [1, 2].

Typically, GBS is a monophasic disease and the disease onset often arises shortly (< 1 month) after an upper respiratory or gastrointestinal tract infection, usually without relapse. Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, mycoplasma pneumonia, Influenza-like illness, HIV and Zika virus are the most common infections reported to precede the onset of GBS [3]. Notably, the association of coronavirus disease 2019 (COVID-19) and different types of neuropathies, such as GBS, have been repeatedly described in the literature in recent years. COVID-19-associated GBS was first brought to the attention of the medical community after a series of 5 patients who had GBS after the onset of COVID-19 was reported in Italy in early 2020 [4]. Since there has been a growing body of evidence introducing COVID-19 as a new infection that can cause GBS [5–7].

On the other hand, GBS has also been described following immunization with various vaccines, but not limited to Semple rabies vaccine and various types of influenza A virus vaccines [8, 9]. The potential link between influenza vaccine and GBS was noted during the H1N1influeza vaccination campaign in 1976 where the increased risk was estimated roughly at one additional case of GBS for every 100,000 people who had been vaccinated [10]. The subsequent studies during 1992–2004 in USA and Canada, confirmed this observation [11, 12]. Further multinational investigations revealed that influenza vaccines, both adjuvant or un-adjuvant forms, could increase the risk of GBS following vaccination [13–16].

Following the COVID-19 pandemic, several groups attempted to design effective vaccines against the virus. In late 2020, the first trials of vaccines showed promising results. Since the beginning of immunization with COVID-19 vaccines, some studies have implicated the association between the COVID-19 vaccine and GBS. In February 2021, Waheed et al. described the first case of GBS following immunization with BNT162b2 mRNA (Pfizer) vaccine [17]. More recently several cases of GBS were reported following Pfizer, Oxford-AstraZeneca (AZV), and Johnson & Johnson (J&J) COVID-19 vaccines [18–21]. Since the beginning of the COVID-19 vaccination program, there have been databases designed to record all the COVID-19 related adverse events. The UK National Immunization Management System database revealed an increased risk of GBS following the first dose of ChAdOx1nCoV-19 (AZV) [22]. However, this risk was not higher than the risk of GBS following COVID-19 infection [22]. The US Vaccine Adverse Event Reporting System, which is a passive reporting system, showed a small but statistically significant risk of GBS associated with Ad26.COV2.S (J & J) COVID-19 vaccine [23]. Here we systematically review the current literature regarding the risk of GBS after COVID-19 vaccination.

This study was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [24], a well-known tool to increase the transparency of reporting systematic reviews. To find relevant studies, we performed a comprehensive search in PubMed, Web of Science, Scopus, as well as a manual search in Google Scholar to find relevant studies. The search query of each source was provided as supplementary materials; nonetheless, we used the following keywords: Guillain-Barré syndrome, COVID-19, SARS-COV-2, Vaccine. We included articles in English between January 2020 and November 2021. All published or pre-published studies that had data regarding the association of COVID-19 and neurological defects, especially GBS in adults who received vaccination against COVID-19 were considered eligible for inclusion regardless of vaccine type (Fig. 1). We also examined large-scale population-based cohort studies, case series, and case reports providing practical details regarding GBS incidence after COVID-19 vaccination.

After retrieving the relevant studies, two reviewers (M.A. and N.M.H.) independently extracted the data from the included studies. The extracted data included general information (author, year, geographic area, study design), demographics data (including age and gender), clinical data (vaccine type, vaccine dose number (first vs second), the time interval between injection and symptom onset, presenting signs and symptoms, GBS subtype), electrophysiological findings, laboratory data (Cerebrospinal fluid analysis, anti-ganglioside antibodies), treatment approaches, need for intubation and clinical outcome. We classified patients’ outcomes into three categories (favorable, partial recovery, and poor). The patients who were discharged with no complications were categorized as ‘favorable’ (complete recovery), those who recovered but needed assistance and further rehabilitation were listed as ‘partial recovery’, and patients who remained bedridden and intubated were classified as ‘poor’ outcome. Moreover, The level of diagnostic certainty was evaluated via Brighton criteria for each case [25]. Due to the qualitative and summative nature of this review and significant variations in study designs and reporting of findings, a meta-analysis and statistical calculations were not performed.

In this study, a total of 88 cases of COVID-19 vaccine-associated GBS were included from 41 studies in 17 countries. Two patients had a previous history of GBS [26, 27]. Five patients received the influenza vaccine in addition to the COVID-19 vaccination [28, 29]. The patients’ age ranged between 14 and 90 years and the mean age was 58.7 ± 16.6 years. The majority of the cases were male (62.5%). The demographic and clinical characteristics were shown in Table 1.

AZV was the most-reported vaccine with 52 cases (59.1%) and Pfizer was the second most-reported vaccine with 20 cases (22.7%). Each of the J&J, Sputnik V, Sinopharm, Moderna, and Sinovac vaccines were reported in 5, 4, 3, 2, and 1 patients, respectively. Most of the cases occurred after the administration of the first dose (79.5%). The mean latency period from vaccination to the onset of the symptoms was 13.9 ± 7.4 days. Limb weakness was the most common symptom reported in 42 patients (47.7%). The sensory disturbance occurred in 34 patients (38.6%). Facial weakness was reported in 24 patients (27.3%). Incidence of bulbar weakness and ophthalmoplegia was 11.4% (10 patients) and 8% (7 patients), respectively. Only one patient suffered sphincter disturbance. Sixty-five patients underwent lumbar puncture. Albuminocytologic dissociation was shown in 65% of the patients. Anti-Ganglioside antibodies including anti-GQ1b, anti-GQ2b, anti-GM1, anti-GM2, anti-GM3, anti-GM4, anti-titin, and anti-sulfatide antibodies were found in 18% of patients who were tested for (5 out of 28).

The most common GBS subtype was acute inflammatory demyelinating polyradiculopathy reported in 38 patients (43.2%). Bifacial weakness with paresthesia (BFP) was the second most common subtype of GBS with an incidence of 15.9% (14 cases). Unspecified classic sensory-motor GBS was reported in 11 patients (12.5%). Acute motor-sensory axonal neuropathy and acute motor axonal neuropathy were reported in 9 (10.2%) and 4 (4.5%) cases, respectively. Other rare subtypes were paraparetic GBS in 4 cases, Miller Fisher syndrome (MFS) in 3 cases, MFS-GBS overlap in 2 cases, pure sensory GBS in 2 subjects, and pure motor GBS in one patient. Patients were divided into four levels based on The Brighton Collaboration definitions with 41 cases in level 1 (46.6%), 24 in level 2 (27.3%), 4 in level 3 (4.5%), and 19 cases in level 4 (21.6%).

The most frequent treatment used as the first-line therapy was intravenous immunoglobulin (IVIG) (n = 61, 69.3%). Plasmapheresis (PLEX) was performed in 13.6% of the cases (n = 12, four cases received PLEX solely, seven received PLEX following IVIG, and one case received PLEX prior to IVIG). Six patients have received corticosteroids (6.8%) while 3 patients were managed conservatively (3.4%). Almost one-fifth of patients were intubated (n = 17). The majority of the patients experienced favorable outcomes (n = 46, 6%) and roughly 22% of the patients had partial improvement (n = 16). Poor outcome was reported in 10 cases (~ 14%) and one person died due to GBS complications (1.1%; Table 2).

Here, we characterized 88 patients who developed GBS following the administration of the COVID-19 vaccine. The majority of cases occurred after receiving a vector-based vaccine with the AZV vaccine being the most reported. The motor deficit was the most common finding among patients who received the AZV vaccine. The latency between vaccination and the onset of neurological symptoms was highly variable (2–30 days; 13.9 ± 7.41 days). The severity of the complications ranged from mild symptoms to severe life-threatening conditions. Thirteen patients required mechanical ventilation. While the favorable outcome was achieved in most cases, some patients had partial recovery and poor outcomes such as unconsciousness and prolonged mechanical ventilation via tracheostomy. A favorable prognosis with a high chance of response to IVIG therapy was in line with our own experience; i.e., we recently reported three cases of post-COVID-19 vaccination GBS of acute motor axonal neuropathy subtype with a considerable short-term recovery in response to treatment with IVIG suggestive for a temporal association between GBS incidence and COVID-19 vaccination [64].

Notably, a high proportion of patients with BFP variant was reported with COVID-19-vaccine associated GBS, compared to previous studies of non-vaccine associated GBS. In the current study, the BFP variant was seen in 15.9% of patients while it generally constitutes less than 5% in GBS cases [65].

General pain and weakness were reported to be the most common adverse events of the AZV COVID-19 vaccine in a recently published large-scale phase III study. Interestingly, only two patients who received the vaccine have shown nervous system disorders; i.e., one patient developed chronic inflammatory demyelinating polyradiculoneuropathy and the other suffered from hypoesthesia [66]. The Pfizer vaccine ranked second for COVID-19-vaccine associated GBS in our study while no neurological adverse events were described in the phase III study [67]. Another interesting notion was that the majority of GBS cases occurred after the second dose of the Pfizer vaccine which was in contrast to the other observations.

In earlier studies, a higher incidence of GBS was observed among those vaccinated with AZV compared to the general population [68, 69] while this was not the case in Pfizer vaccinated individuals. In a self-controlled case study using the English national immunization database of COVID-19 vaccination, a total of 187 cases of GBS (out of more than 32 million subjects) have been observed during 1–28 days following vaccination with the first dose of either AZV or Pfizer vaccines (incidence ~ 0.6 cases per 100,000 first dose vaccination). No association was found between the Pfizer vaccine and the risk of GBS in this period. However, an increased risk of GBS was found after AZV vaccination (IRR, 2.04; 95% CI: 1.60–2.60). Nevertheless, the risk of GBS was substantially higher within 28 days of a positive COVID-19 test (IRR, 5.25; 95% CI: 3.00–9.18) [69].

In an interim analysis of surveillance data of COVID-19 vaccines, Hanson et al. compared the adjusted rate ratio (RR) of GBS incidence in the other vector-based vaccine (J&J) vs. mRNA vaccines (Pfizer, Moderna) during the 1–21 days post-vaccination period. The adjusted RR (adjusted for age, sex, race/ethnicity, and calendar day) of GBS following J&J vs. mRNA vaccines was 20.56 showing a significantly higher risk for J&J recipients compared to mRNA vaccines with 15.5 excess GBS cases per million J&J vaccines (95% CI: 6.94–64.66, P < .001) [70].

Very rarely central nervous system autoimmune diseases were also described in association with the COVID-19 vaccine [71]. Different potential mechanisms can be suggested for the possible association of autoimmune diseases after vaccination. This may include the similarity of vaccine epitopes with myelin or axon epitopes and triggering cellular and humoral immune responses, degradation of axon or myelin membranes due to direct exposure of vaccine virus or vaccine-related products, and chances of genetic predisposition [72]. The presence of a temporal association between vaccination and GBS is by no means adequate evidence for a causal relationship between the two, however suggestive of one. Regardless, a wide range of time intervals between the vaccination and the occurrence of GBS symptoms (3 hours to 39 days) seen in this study again suggests a complex multifactorial relationship rather than a direct link between the two.

GBS is a rare neurologic disease and a few cases of GBS have been reported worldwide in association with vaccination against COVID-19. The available data is insufficient to determine the precise pathophysiology behind this observation. In this review, we provided a summary of current evidence on clinical and neurophysiological characteristics of post-COVID-19 vaccination GBS. This information helps physicians in early diagnosis and appropriate management of this rare type of GBS and enables them to have an evidence-based discussion with patients, particularly when dealing with vaccine hesitancy. Furthermore, our data add to the growing body of evidence suggestive of an association between various COVID-19 vaccines and the occurrence of GBS. Nonetheless, the benefits of vaccines against COVID-19 certainly outweigh the potential risk of GBS with a prognosis that proved to be favorable in the majority of cases.

Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article.

Author Contributions: All authors contributed to the study conception and design. Material preparation, data extraction and assessment were performed by [Meysam Abolmaali], [Arman Karimi Behnagh] and [Negin Mahmoudi Hamidabad]. The first draft of the manuscript was written equally by [Zahra Mirzaasgari], [Meysam Abolmaali], [Arman Karimi Behnagh] and [Negin Mahmoudi Hamidabad] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Raahimi MM, Kane A, Moore CE, Alareed AW. Late onset of Guillain-Barré syndrome following SARS-CoV-2 infection: part of ‘long COVID-19 syndrome’? BMJ Case Reports CP. 2021;14:e240178.
Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. 2016;388:717–27.
Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. The Lancet. 2021.
Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain–Barré syndrome associated with SARS-CoV-2. New England Journal of Medicine. 2020;382:2574–6.
Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020;382:2574–6.
Abolmaali M, Heidari M, Zeinali M, Moghaddam P, Ghamsari MR, Makiani MJ, et al. Guillain–Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series. Journal of Clinical Neuroscience. 2021;83:119–22.
Palaiodimou L, Stefanou MI, Katsanos AH, Fragkou PC, Papadopoulou M, Moschovos C, et al. Prevalence, clinical characteristics and outcomes of Guillain – Barré syndrome spectrum associated with COVID-19: A systematic review and meta‐analysis. European Journal of Neurology. 2021.
Petráš M, Králová Lesná I, Dáňová J, Čelko AM. Is an increased risk of developing Guillain–Barré syndrome associated with seasonal influenza vaccination? A systematic review and meta-analysis. Vaccines. 2020;8:150.
Capasso A, Ompad DC, Vieira DL, Wilder-Smith A, Tozan Y. Incidence of Guillain-Barré Syndrome (GBS) in Latin America and the Caribbean before and during the 2015–2016 Zika virus epidemic: A systematic review and meta-analysis. PLoS neglected tropical diseases. 2019;13:e0007622.
Safranek TJ, Lawrence DN, Kuriand LT, Culver DH, Wiederholt WC, Hayner NS, et al. Reassessment of the association between Guillain-Barré syndrome and receipt of swine influenza vaccine in 1976–1977: results of a two-state study. American journal of epidemiology. 1991;133:940–51.
Haber P, DeStefano F, Angulo FJ, Iskander J, Shadomy SV, Weintraub E, et al. Guillain-Barré Syndrome Following Influenza Vaccination. JAMA. 2004;292:2478–81.
Juurlink DN, Stukel TA, Kwong J, Kopp A, McGeer A, Upshur RE, et al. Guillain-Barre syndrome after influenza vaccination in adults: a population-based study. Arch Intern Med. 2006;166:2217–21.
Andrews N, Stowe J, Al-Shahi Salman R, Miller E. Guillain-Barre syndrome and H1N1 (2009) pandemic influenza vaccination using an AS03 adjuvanted vaccine in the United Kingdom: self-controlled case series. Vaccine. 2011;29:7878–82.
De Wals P, Deceuninck G, Toth E, Boulianne N, Brunet D, Boucher RM, et al. Risk of Guillain-Barre syndrome following H1N1 influenza vaccination in Quebec. JAMA. 2012;308:175–81.
Dieleman J, Romio S, Johansen K, Weibel D, Bonhoeffer J, Sturkenboom M, et al. Guillain-Barre syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: multinational case-control study in Europe. BMJ. 2011;343:d3908.
Greene SK, Rett M, Weintraub ES, Li L, Yin R, Amato AA, et al. Risk of confirmed Guillain-Barre syndrome following receipt of monovalent inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine Safety Datalink Project, 2009–2010. Am J Epidemiol. 2012;175:1100–9.
Waheed S, Bayas A, Hindi F, Rizvi Z, Espinosa PS. Neurological complications of COVID-19: Guillain-Barre syndrome following Pfizer COVID-19 vaccine. Cureus. 2021;13.
Aomar-Millán IF, de Victoria-Carazo JM, Peregrina-Rivas J, Villegas-Rodríguez I. COVID-19, Guillain-Barré syndrome, and the vaccine. A dangerous combination. Revista clinica espanola. 2021.
Bonifacio GB, Patel D, Cook S, Purcaru E, Couzins M, Domjan J, et al. Bilateral facial weakness with paraesthesia variant of Guillain-Barré syndrome following Vaxzevria COVID-19 vaccine. Journal of Neurology, Neurosurgery & Psychiatry. 2021.
James J, Jose J, Gafoor VA, Smita B, Balaram N. Guillain-Barré syndrome following ChAdOx1 nCoV‐19 COVID‐19 vaccination: A case series. Neurology and Clinical Neuroscience. 2021;9:402–5.
Jain E, Pandav K, Regmi P, Michel G, Altshuler I. Facial diplegia: a rare, atypical variant of Guillain-Barré syndrome and Ad26. COV2. S Vaccine. Cureus. 2021;13.
Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med. 2021;27:2144–53.
Woo EJ, Mba-Jonas A, Dimova RB, Alimchandani M, Zinderman CE, Nair N. Association of Receipt of the Ad26.COV2.S COVID-19 Vaccine With Presumptive Guillain-Barré Syndrome, February-July 2021. Jama. 2021;326:1606–13.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
Ghazanfar H, Qazi R, Ghazanfar A, Iftekhar S. Significance of Brighton Criteria in the Early Diagnosis and Management of Guillain-Barré Syndrome. Cureus. 2020;12:e8318-e.
Ling L, Bagshaw SM, Villeneuve P-M. Guillain–Barré syndrome after SARS-CoV-2 vaccination in a patient with previous vaccine-associated Guillain–Barré syndrome. CMAJ. 2021;193:E1766-E9.
Finsterer J. Exacerbating Guillain–Barré Syndrome Eight Days after Vector-Based COVID-19 Vaccination. Case Reports in Infectious Diseases. 2021;2021.
García-Grimshaw M, Michel-Chávez A, Vera-Zertuche JM, Galnares-Olalde JA, Hernández-Vanegas LE, Figueroa-Cucurachi M, et al. Guillain-Barré syndrome is infrequent among recipients of the BNT162b2 mRNA COVID-19 vaccine. Clinical Immunology. 2021;230:108818.
Oo WM, Giri P, De Souza A. AstraZeneca COVID-19 vaccine and Guillain-Barré Syndrome in Tasmania: A causal link? Journal of neuroimmunology. 2021;360:577719.
Abičić A, Adamec I, Habek M. Miller Fisher syndrome following Pfizer COVID-19 vaccine. Neurological Sciences. 2021:1–3.
Allen CM, Ramsamy S, Tarr AW, Tighe PJ, Irving WL, Tanasescu R, et al. Guillain–Barré syndrome variant occurring after SARS-CoV‐2 vaccination. Annals of neurology. 2021;90:315–8.
Azam S, Khalil A, Taha A. Guillain-Barré syndrome in a 67-year-old male post COVID-19 vaccination (Astra Zeneca). American Journal of Medical Case Reports. 2021;9:424–7.
Bax F, Gigli GL, Belgrado E, Brunelli L, Valente M. Guillain–Barré syndrome following Covid-19 immunization: a report of two cases. Acta Neurologica Belgica. 2021:1–3.
Bonifacio GB, Patel D, Cook S, Purcaru E, Couzins M, Domjan J, et al. Bilateral facial weakness with paraesthesia variant of Guillain-Barré syndrome following Vaxzevria COVID-19 vaccine. Journal of Neurology, Neurosurgery & Psychiatry. 2022;93:341–2.
Bouattour N, Hdiji O, Sakka S, Fakhfakh E, Moalla K, Daoud S, et al. Guillain-Barré syndrome following the first dose of Pfizer-BioNTech COVID-19 vaccine: case report and review of reported cases. Neurological Sciences. 2021:1–7.
Dang YL, Bryson A. Miller-Fisher Syndrome and Guillain-Barre Syndrome overlap syndrome in a patient post Oxford-AstraZeneca SARS-CoV-2 vaccination. BMJ Case Reports CP. 2021;14:e246701.
da Silva GF, da Silva CF, Oliveira RENdN, Romancini F, Mendes RM, Locks A, et al. Guillain–Barré syndrome after coronavirus disease 2019 vaccine: A temporal association. Clinical and Experimental Neuroimmunology. 2021.
Hasan T, Khan M, Khan F, Hamza G. Case of Guillain-Barré syndrome following COVID-19 vaccine. BMJ Case Reports CP. 2021;14:e243629.
Hughes DL, Brunn JA, Jacobs J, Todd PK, Askari FK, Fontana RJ. Guillain-Barré Syndrome After COVID‐19 mRNA Vaccination in a Liver Transplantation Recipient With Favorable Treatment Response. Liver Transplantation. 2022;28:134–7.
Introna A, Caputo F, Santoro C, Guerra T, Ucci M, Mezzapesa DM, et al. Guillain-Barré syndrome after AstraZeneca COVID-19-vaccination: a causal or casual association? Clinical Neurology and Neurosurgery. 2021;208:106887.
Kanabar G, Wilkinson P. Guillain-Barré syndrome presenting with facial diplegia following COVID‐19 vaccination in two patients. BMJ Case Reports CP. 2021;14:e244527.
Karimi N, Boostani R, Fatehi F, Panahi A, Okhovat AA, Ziaadini B, et al. Guillain-Barre Syndrome and COVID-19 Vaccine: A Report of Nine Patients. Basic and Clinical Neuroscience. 2021;12:703–10.
Loza AMM, Holroyd KB, Johnson SA, Pilgrim DM, Amato AA. Guillain-Barré syndrome in the placebo and active arms of a COVID-19 vaccine clinical trial: temporal associations do not imply causality. Neurology. 2021;96:1052–4.
Malamud E, Otallah SI, Caress JB, Lapid DJ. Guillain-Barré Syndrome After COVID-19 Vaccination in an Adolescent. Pediatric neurology. 2022;126:9–10.
Maramattom BV, Krishnan P, Paul R, Padmanabhan S, Cherukudal Vishnu Nampoothiri S, Syed AA, et al. Guillain-Barré syndrome following ChAdOx1‐S/nCoV‐19 vaccine. Annals of neurology. 2021;90:312–4.
Masuccio FG, Comi C, Solaro C. Guillain–Barrè syndrome following COVID-19 vaccine mRNA-1273: a case report. Acta Neurologica Belgica. 2021:1–3.
Matarneh AS, Al-battah AH, Farooqui K, Ghamoodi M, Alhatou M. COVID‐19 vaccine causing Guillain‐Barre syndrome, a rare potential side effect. Clinical Case Reports. 2021;9:e04756.
McKean N, Chircop C. Guillain-Barré syndrome after COVID-19 vaccination. BMJ Case Reports CP. 2021;14:e244125.
Michaelson NM, Lam T, Malhotra A, Schiff ND, MacGowan DJL. Miller Fisher Syndrome Presenting After a Second Dose of Pfizer-BioNTech Vaccination in a Patient With Resolved COVID-19: A Case Report. Journal of Clinical Neuromuscular Disease. 2021;23:113–5.
Min YG, Ju W, Ha Y-E, Ban J-J, Lee SA, Sung J-J, et al. Sensory Guillain-Barre syndrome following the ChAdOx1 nCov-19 vaccine: Report of two cases and review of literature. Journal of neuroimmunology. 2021;359:577691.
Morehouse ZP, Paulus A, Jasti SA, Bing X. A Rare Variant of Guillain-Barre Syndrome Following Ad26. COV2. S Vaccination. Cureus. 2021;13.
Nasuelli NA, De Marchi F, Cecchin M, De Paoli I, Onorato S, Pettinaroli R, et al. A case of acute demyelinating polyradiculoneuropathy with bilateral facial palsy after ChAdOx1 nCoV-19 vaccine. Neurological Sciences. 2021;42:4747–9.
Nishiguchi Y, Matsuyama H, Maeda K, Shindo A, Tomimoto H. Miller Fisher syndrome following BNT162b2 mRNA coronavirus 2019 vaccination. BMC neurology. 2021;21:1–6.
Ogbebor O, Seth H, Min Z, Bhanot N. Guillain-Barré syndrome following the first dose of SARS-CoV-2 vaccine: A temporal occurrence, not a causal association. IDCases. 2021;24:e01143.
Oo WM, Giri P, de Souza A. AstraZeneca COVID-19 vaccine and Guillain- Barré Syndrome in Tasmania: A causal link? J Neuroimmunol. 2021;360:577719.
Osowicki J, Morgan H, Harris A, Crawford NW, Buttery JP, Kiers L. Guillain-Barré Syndrome in an Australian State Using Both mRNA and Adenovirus-Vector SARS-CoV-2 Vaccines. Ann Neurol. 2021;90:856–8.
Patel SU, Khurram R, Lakhani A, Quirk B. Guillain-Barre syndrome following the first dose of the chimpanzee adenovirus-vectored COVID-19 vaccine, ChAdOx1. BMJ Case Rep. 2021;14.
Prasad A, Hurlburt G, Podury S, Tandon M, Kingree S, Sriwastava S. A Novel Case of Bifacial Diplegia Variant of Guillain-Barré Syndrome Following Janssen COVID-19 Vaccination. Neurol Int. 2021;13:404–9.
Razok A, Shams A, Almeer A, Zahid M. Post-COVID-19 vaccine Guillain-Barré syndrome; first reported case from Qatar. Ann Med Surg (Lond). 2021;67:102540.
Rossetti A, Gheihman G, O'Hare M, Kosowsky JM. Guillain-Barré Syndrome Presenting as Facial Diplegia after COVID-19 Vaccination: A Case Report. J Emerg Med. 2021;61:e141-e5.
Scendoni R, Petrelli C, Scaloni G, Logullo FO. Electromyoneurography and laboratory findings in a case of Guillain-Barré syndrome after second dose of Pfizer COVID-19 vaccine. Hum Vaccin Immunother. 2021;17:4093–6.
Trimboli M, Zoleo P, Arabia G, Gambardella A. Guillain-Barré syndrome following BNT162b2 COVID-19 vaccine. Neurol Sci. 2021;42:4401–2.
Tutar NK, Eyigürbüz T, Yildirim Z, Kale N. A variant of Guillain-Barre syndrome after SARS-CoV-2 vaccination: AMSAN. Ideggyogyaszati Szemle. 2021;74:286–8.
Tabatabaee S, Rezania F, Alwedaie SMJ, Malekdar E, Badi Z, Tabatabaei SM, et al. Post COVID-19 vaccination Guillain-Barre syndrome: three cases. Human Vaccines & Immunotherapeutics. 2022:1–5.
Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 2019;15:671–83.
Falsey AR, Sobieszczyk ME, Hirsch I, Sproule S, Robb ML, Corey L, et al. Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine. N Engl J Med. 2021;385:2348–60.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. 2020;383:2603–15.
Perez-Lloret S, Petrovsky N, Alami A, Crispo J, Mattison D, Otero-Losadsa M, et al. Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom. medRxiv. 2021.
Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nature medicine. 2021;27:2144–53.
Hanson KE, Goddard K, Lewis N, Fireman B, Myers TR, Bakshi N, et al. Guillain-Barré Syndrome after COVID-19 Vaccination in the Vaccine Safety Datalink. medRxiv. 2021.
Maroufi SF, Naderi Behdani F, Rezania F, Tanhapour Khotbehsara S, Mirzaasgari Z. Longitudinally extensive transverse myelitis after Covid-19 vaccination: case report and review of literature. Human Vaccines & Immunotherapeutics. 2022:1–4.
Vadalà M, Poddighe D, Laurino C, Palmieri B. Vaccination and autoimmune diseases: is prevention of adverse health effects on the horizon? Epma j. 2017;8:295–311.

Table 1

No.

Authors

Country

Age/Sex

Vaccine/dose

Onset time (Day)

GBS subtype

Electrophysiologic finding

Albuminocytological dissociation

Ganglioside Ab

MRI

Brighton collaboration level

Treatment

Intubation

Outcome

Abičić et al. [30]

Croatia

24/F

Pfizer/1

MFS

+ (Anti GQ1b)

- Prednisolone, IVIg

Allen et al. [31]

54/M

20/M

57/M

55/M

AZV/1

BFP

See below^a

See below^b

Normal

See below^c

Normal

Rt facial nerve enhancement

- Prednisolone

- IVIg

- Conservative

Aomar et al. [18]

Spain

77/M

Pfizer/1

AMSAN

- IVIg, PLEX

Azam et al. [32]

67/M

AZV/1

AIDP

Bilateral enhancement in facial nerves

- IVIg

Bax et al. [33]

Italy

90/M

51/F

Pfizer/2

AZV/1

AMSAN

AIDP

AMSAN

AIDP

+^d

- IVIg

Bonifacio et al. [34]

66/M

43/M

51/M

71/F

53/M

AZV/1

BFP

Demyelinating

+/GM3

see below^c

Normal

- IVIg

- NR

Bouattour et al. [35]

Tunisia

67/M

Pfizer/1

AIDP

- IVIg

Dang et al. [36]

Australia

63/M

AZV/1

MF&GBS overlap

Bilateral enhancement

of CNVII & III

- IVIg

da Silva et al. [37]

Brazil

62/F

AZV/1

Classic SM

- IVIg

Finsterer et al. [27]

Austria

32/M

Vector based/1

AIDP

Non-specific bilateral white matter hyperintensity

- IVIg

García-Grimshaw et al. [28]

Mexico

33/M

25/M

53/F

72/M

31/M

67/F

81/F

Pfizer/1

AIDP

AMAN

AIDP

AMAN

AIDP

AMAN

AIDP

AMAN

AIDP

- IVIg

Poor

Dead

Hasan et al. [38]

62/F

AZV/1

AIDP

Normal

- IVIg

Poor

Hughes et al. [39]

USA

65/M

Pfizer/1

AIDP

Normal

- IVIg

Introna et al. [40]

Italy

62/M

AZV/1

AIDP

AMSAN

+ /GM1

Normal

- IVIg

Jain et al. [21]

USA

65/F

J & J

BFP

Normal

- IVIg, PLEX

James et al. [20]

India

60/M

66/M

54/F

AZV/1

AMSAN

AIDP

AMSAN

AIDP

-Normal

-Nonspecific^e

-Normal

- IVIg

- IVIg, IVMP

Kanabar et al. [41]

61/F

56/M

AZV/1

AIDP

- IVIg

Karimi et al. [42]

Iran

38/M

87/M

52/M

48/F

26/F

44/M

76/M

79/M

Sputnik V

Sputnik V/1

Sinopharm/1

Sputnik V

Sinopharm/2

AZV/1

Sinopharm/1

AZV/1

BFP

AIDP

Classic SM

AIDP

AMSAN

AMAN

AMSAN

Prolong R1&R2 latency

AIDP

AMSAN

AMAN

AMSAN

-Normal

-NP

- PLEX

- IVIg

- IVIg, PLEX

- IVIg

- PLEX

Ling et al. [26]

Canada

63/M

AZV/1

AIDP

Normal

- IVIg, PLEX

Loza et al. [43]

USA

60/F

J&J

MFS and classic overlap

Absent F waves &H reflex

Cauda equina enhancement

- IVIg

Malamud et al. [44]

USA

14/M

Pfizer/2

AIDP

- IVIg

Maramottom et al. [45]

India

43/F

67/F

53/F

68/F

70/M

69/F

AZV/1

AIDP

AMSAN

AIDP

AMSAN

AIDP

Normal

- IVIg

- IVIg, PLEX

- IVIg

- IVIg, PLEX

- IVIg

Poor

Masuccio et al. [46]

Italy

80/M

Moderna/2

AIDP

Normal

- IVIg

Matarneh et al. [47]

Qatar

61/M

Moderna/2

Pure motor

Demyelinating motor neuropathy

- IVIg

McKean et al. [48]

Malta

48/M

AZV/1

AIDP

Normal

- IVIg, Prednisolone

Michaelson et al. [49]

USA

78/M

Pfizer/2

MFS

Equivocal

Normal

- IVIg

Min et al. [50]

Korea

58/M

37/F

AZV/1

Sensory GBS

see below^f

Normal

- Gabapentin

- Gabapentin, Duloxetine, Tramadol

Morehouse et al. [51]

USA

49/F

J&J

Classic SM

Small punctate foci

- IVIg, PLEX

Poor

Nasuelli et al. [52]

Italy

59/M

AZV/1

AIDP

Normal

- IVIg

Nishiguchi et al. [53]

Japan

71/M

Pfizer/1

MFS

Normal

- IVIg

Ogbebor et al. [54]

USA

86/F

Pfizer/1

Paraparetic

Normal

- IVIg

Oo et al. [55]

Australia

51/M

65/F

66/M

AZV/1

AIDP

Nonspecific^g

- IVIg, PLEX

- IVIg

Poor

Osowicki et al. [56]

Australia

75/F

77/F

57/F

57/M

52/F

54/M

80/F

72/M

59/M

69/M

72/F

66/M

63/M

70/M

AZV/1

AIDP

Paraparetic

BFP

AIDP

Paraparetic

Classic

AMSAN

AIDP

AMSAN

- NR

Patel et al. [57]

37/M

AZV/1

Classic SM

Patchy attenuation of motor response

Prominent ventral

cauda equina nerve root enhancement

- IVIg

Prasad et al. [58]

USA

41/M

J&J

BFP

demyelinating

Normal

- IVIg

Razok et al. [59]

Qatar

73/M

Pfizer/2

Paraparetic

Absent bilateral H reflex

Bilateral lumbar nerve root enhancement

- IVIg

Rossetti et al. [60]

USA

38/M

J&J

BFP

Focal bilateral enhancement of the internal auditory canal, fundi and cisternal segments of the trigeminal nerves

- IVIg

Scendoni et al. [61]

Italy

82/F

Pfizer/2

AIDP

+^h

- IVIg

Trimboli et al. [62]

Italy

25/F

Pfizer/2

AIDP

- IVIg

Tutar et al. [63]

Turkey

76/M

CoronaVac/2

AMSAN

Normal

- IVIg

Waheed et al. [17]

USA

82/F

Pfizer/1

Classic SM

cauda equina nerve root enhancement

- IVIg

GBS, Guillain–Barré Syndrome; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; MRI, magnetic resonance imaging; AZV, AstraZeneca Vaccine; J&J, Johnson & Johnson; NR, not reported; NT, not tested; NP, not performed; AIDP, acute inflammatory demyelinating polyradiculopathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor-sensory axonal neuropathy; BFP, bifacial weakness with paresthesia; MFS, Miller Fisher syndrome; IVIg, intravenous immunoglobulin; PLEX, plasmapheresis; CR, complete recovery; PR, partial recovery; SM, sensory-motor; rt, right; lt, left; SNAP, sensory nerve action potential; CMAP, compound muscle action potential; IVMP, intravenous methylprednisolone; CN, cranial nerve

^aDecreased facial CMAP amplitude, denervation in facial muscles

^bDenervation in facial muscles

^cBilateral enhancement in facial nerves

^dAnti-GQ1b, anti-titin

^eTiny hyperintensity in Rt anterolateral spinal cord

^fDecreased Rt/Lt sural SNAP amplitude, temporal dispersion in Lt and absent Rt peroneal CMAP

^gNonspecific white matter hyperintensities

^hAnti-sulfatide, anti- GM2, anti-GM4

Table 2

Variable			Total cases
Sex (%)	Female	33 (37.5)	88
Sex (%)	Male	55 (62.5)	88
Age_,years, mean ± SD		57.80 ± 16.59
Vaccine Name (%)	AstraZeneca	52 (59.1)	88
	Pfizer & BioNTech	20 (22.7)
	Moderna	2 (2.3)
	Johnson & Johnson	5 (5.7)
	Sputnik	4 (4.5)
	Sinopharm	3 (3.4)
	SinoVac	1 (1.1)
	Unknown vector-based	1 (1.1)
Vaccination Dose	First	70 (79.5)	88
Vaccination Dose	Second	10 (11.4)	88
Latency Period_,days, mean ± SD (From vaccination to symptom onset)		13.90 ± 7.41	87
Symptoms (%)	Facial weakness	24 (27.3)	88
	Limb weakness	42 (47.7)
	Bulbar palsy	10 (11.4)
	Ophthalmoplegia	7 (8)
	Sensory disturbances	34 (38.6)
	Sphincter weakness	1 (1.1)
CSF Protein (%)	Elevated	57 (87.7)	65
CSF Protein (%)	Normal	8 (12.3)	65
Ganglioside Antibody (%)	Positive	5 (17.9)	28
Ganglioside Antibody (%)	Negative	23 (82.1)	28
GBS Subtype (%)	AIDP	38 (43.2)	88
	AMAN	4 (4.5)
	AMSAN	9 (10.2)
	BFP	14 (15.9)
	Paraparetic	4 (4.5)
	MFS-GBS overlap syndrome	2 (2.2)
	Pure motor	1 (1.1)
	Pure sensory	2 (2.3)
	Unspecified classic sensory-motor	11 (12.5)
	Miller Fisher Syndrome	3 (3.4)
Treatment (%)	IVIg	61 (69.3)	88
	Glucocorticoids	6 (6.8)
	Plasmapheresis	12 (13.6)
	Conservative	3 (3.4)
Intubation (%)	Yes	17 (25.4)	67
Intubation (%)	No	50 (74.6)	67
Outcome (%)	Favorable	46 (63)	73
	Partial improvement	16 (21.9)
	Poor	10 (13.7)
	Death	1 (1.4)
Brighton Collaboration Level (%)	1	41 (46.6)	88
	2	24 (27.3)
	3	4 (4.5)
	4	19 (21.6)
CSF, cerebrospinal fluid; GBS, Guillain-Barre syndrome; AIDP, acute inflammatory demyelinating polyradiculopathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor-sensory axonal neuropathy; BFP, bifacial weakness with paresthesia; MFS, Miller Fisher syndrome; IVIg, Intravenous immune globulin

Searchstrategy.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

Guillain-Barré Syndrome in Association with COVID-19 Vaccination: A Systematic Review

Status:

Version 1

Abstract

Figures

Introduction

Method And Materials

Results

Discussion

Conclusion

Declarations

References

Tables

Supplementary Files

Status:

Version 1