Guillain-Barre syndrome following COVID-19 vaccination: a study of 70 case reports

Highlights The study provides new insight into the development of Guillain–Barre ´ syndrome (GBS) following post-vaccination. In the present review article, we reviewed the onset of symptoms, clinical features, previous comorbidities, investigations, and outcomes of 103 patients aged between 13 and 87 years with the COVID-19-associated GBS spectrum. The treatment included intravenous immunoglobulins, steroids, Plasmapheresi and physiotherapy. The clinical consequences of GBS and incomplete recovery of patients in this study emphasize the need for vigilance and in-depth research in this regard. Guillain–Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy characterized clinically by progressive limb weakness. It is the most common cause of acute flaccid paralysis with an incidence of about 2 in 100 000 people/per year 1 . Diagnosis of this disease requires a combination of clinical findings supported by nerve conduction studies (NCS) and cerebrospinal fluid (CSF) examination. It is diagnosed by Brighton criteria and the case definitions for Guillain–Barre syndrome 2 have been attached to Table 1 Despite prompt treatment, there may be no full recovery. Therefore, aetiological factors for the occurrence of GBS should be investigated and controlled. Diagnostic criteria and Brighton case definition for Guillian–Barre syndrome + Present; - absent ; +/− present or absent CSF, cerebrospinal fluid; GBS, Guillian–Barre syndrome; NCS, nerve conduction studies. If CSF is not collected or results not available, nerve electrophysiology results must be consistent with the diagnosis Guillain–Barre´ syndrome. Even though the exact pathogenesis is unknown, it is believed that an autoimmune response preceding a viral, or bacterial infection or vaccination plays a role in the development of GBS. The first epidemiological link between vaccines and GBS was highlighted in 1976 when was reported an increased GBS risk among individuals who received the swine flu vaccine 3 . Speculative studies suggest a post-vaccination immune response attributing to the production of antibodies and T cells that cross-react with ganglioside at nerve membranes due to molecular mimicry 4 . There are rare reports of GBS after the administration of rabies, influenza, and polio vaccines. SARS-CoV-2 vaccination-related adverse effects range from mild-moderate to severe neurological dysfunction because of the presence of contaminated proteins which may elicit anti-ganglioside antibodies 5 . The probable cause of GBS occurrence post-vaccination with AstraZeneca is the attachment of adenovirus-vector spike proteins to ganglioside receptors and consequent anti-ganglioside antibody formation 6 . Other adenoviral vector vaccines such as Sputnik V, Janssen, and Convidecia may have a similar mechanism. In mRNA vaccines such as Pfizer, the mRNA recognizes the spike protein and generates antibodies which may trigger autoantibody formation against myelin and lead to GBS 7 . mRNA enters the human cell and instructs the cells to identify the spike protein found on the surface of SARS-COV-2, the virus that causes COVID-19. Our bodies then recognize the spike protein as an invader and produce antibodies against it. Later, if these antibodies encounter the actual virus, they are ready to recognize and kill the virus before it can cause illness. In some patients, this immune response can trigger autoimmune processes that lead to the production of antibodies against the myelin and cause GBS. To date, the FDA approved three double-dose vaccines for the prevention of COVID-19 infection [BNT162b2 (Pfizer); mRNA-1273 (Moderna); Ad26.COV2. S (Johnson & Johnson)] 8 . The safety profile of the COVID vaccines is still being established and the neurological side effects are of utmost concern. Recent case reports have shown an occurrence of GBS post-COVID vaccination although much regarding the nature of the association and the characteristics of GBS in this situation remains unclear. GBS is more frequently reported in adenovirus-vector vaccines, but there are also several case reports of GBS with mRNA vaccines 9 . To bridge the knowledge gap, here we present a comprehensive narrative of 103 studies on GBS involvement.

In the future, we can collect the blood samples of the patient and monitor their immune response to the particular vaccine by using laboratory techniques like enzyme-linked immunosorbent assay (ELISA), hemagglutination test, polymerase chain reaction (PCR), etc. before going through vaccination. Patients with prior infections like CMV, EBV, Zika virus, or other infections should avoid administering the vaccine before recovery. Furthermore, researchers may explore the potential differences in GBS incidence and characteristics between primary vaccine administration and booster shots. Moving forward, the comparison of the clinical features of GBS across various vaccine types may be studied.

No funding was received for this study.

Informed consent was not required for this review.

Ethical approval was not required for this review.

We searched PubMed, Google Scholar, Cochrane, and Embase for case reports using search terms “Guillain-Barré Syndrome,” “COVID-19 Vaccines,” “COVID-19,” and “Case report” published till 1st August 2023. The title and abstract were screened and through discussions by three authors, the eligible full-text articles were only included for this review. We included case reports which were free full texts that focused on presenting symptoms, diagnosis, treatment, and pathophysiologic mechanisms linked to our issue. Those articles that were not free and which did not show the linkage between GBS and COVID-19 vaccination were excluded. Editorials, Reviews, and Letters to the Editor were excluded. We used Statistical Package for Social Sciences (SPSS) version 20 and Microsoft Office Excel 2019 for statistical analysis.

We conducted a comprehensive review of published case reports and documented 70 published case reports from peer-reviewed journals. A total of 103 individuals were described on those case reports; among them, the highest number that is 48 people developed GBS following AstraZeneca (Vaxzervia) vaccination followed by 23 after Pfizer, 8 after Johnson& Johnson, Moderna, 6 after Sinopharm, 5 after Sputnik, 2 after Sinovac, Corbevax and one after Vector-based COVID-19 vaccine shown in Figure 1 . Frequency of Guillain–Barre syndrome following different types of COVID-19 vaccine. Clinical features along with the management of GBS following COVID-19 vaccination are present in the Table 2 . Clinical features and management of GBS following COVID vaccine AIDP, Acute inflammatory demyelinating polyneuropathy; CT, computed tomography; CBC, complete blood count; GBS, Guillian–Barre syndrome; LMN, lower motor neuron; PCR, polymerase chain reaction. Incidence of case reports of GBS development following the COVID-19 vaccine was reported from 28 countries and among them, the highest,19 were from the USA following the second highest, 9 from Argentina and India and 8 were from the UK and the remaining from other countries are shown in Fig. 2 . Reports of Guillain–Barre syndrome from countries following COVID-19 vaccination. A wide variation of age among the patients who developed GBS after receiving the corresponding COVID-19 vaccine was seen. So, the median age was found to be 53±20 interquartile range (IQR) years. Elderly people seem to be affected more may be due to gradual loss of nerve myelination with increased age. 47 people had pre-existing chronic illnesses and the remaining 57 did not have any illness before the development of GBS. Although chronic illness reduces the immunity of a person and is prone to another disease; here it didn’t show such importance. Also, there is a male predominance of 62% (64/103) compared to a female of 36% (39/103). The median time between receiving the COVID-19 vaccine and the onset of symptoms was noted to be 13.08± 11 IQR days.

Not applicable.

Biki Kumar Sah.

The medical sciences have been put to the test by the COVID-19 epidemic. Our attempts to prevent and treat this disease have been closely correlated with our understanding of the disease and its aetiology. The creation and use of these vaccinations in just two years is evidence of how quickly evidence-based medicine is developing and integrating with the healthcare system. Medical practitioners should be aware of any neurological side effects after receiving the SARS-CoV-2 vaccine, even if they are rare. A high level of awareness and quick action are required in these situations. To demonstrate a clear causal relationship between GBS with the presently advised immunizations, more rigorous research is necessary. Until then, the advantages of COVID-19 protection for both persons and society outweigh the apprehensive danger of these unfavourable outcomes by a wide margin.

The epidemiological relationship between COVID-19 vaccination and GBS is becoming clearer. The most common symptom of GBS, an autoimmune disorder of the peripheral nerve system, is rapidly progressing ascending paralysis 46 . This study will be crucial for promoting early detection and treatment because GBS complications can result in serious morbidity and death 78 . We reviewed the onset of symptoms, clinical features, previous comorbidities, investigations, and outcomes of 103 patients aged between 13 and 87 with the COVID-19-associated GBS spectrum. Our study demonstrated a correlation between the COVID-19 vaccine and GBS; patients reported ascending progressive paraesthesia of distal lower and upper limbs following the administration of various COVID-19 vaccines. Most instances of the condition occurred following the administration of vector-based vaccines, with the AstraZeneca vaccine being the most frequently cited. The most frequent symptom among those who received the AstraZeneca vaccine was a motor deficit. The time frame between vaccination and the appearance of neurological symptoms varied greatly, ranging from 1 to 60 days with a median of 13± 11 IQR days. The majority of symptoms appeared after the first dose and only 23 cases were from the second dose and 2 cases after the third dose of vaccination. The complications varied in severity, from mild symptoms to severe and potentially life-threatening conditions. In eight cases, the patients presented with sudden onset back pain before weakness in the lower limbs. In another issue, the clinical manifestations of GBS were facial diplegia which may be associated with other systemic diseases like Lyme disease, sarcoidosis, and diabetes 79 . The Pfizer vaccine was found to be second in ranking for its association with GBS related to COVID-19 vaccines, even though no neurological side effects were reported in the phase III clinical trial 6 . A noteworthy observation was that the majority of GBS cases happened after receiving the second dose of the Pfizer vaccine, which was different from other vaccines. It has been previously reported, albeit rarely, that the COVID-19 vaccine may be associated with autoimmune diseases affecting the central nervous system 80 . There are various theories about how this association may occur, such as similarities between vaccine components and myelin or axon components that trigger immune responses, exposure to vaccine viruses or vaccine-related products leading to the degradation of the axon or myelin membranes, and genetic predisposition 81 . Although the presence of a temporal link between vaccination and GBS suggests a possible causal relationship, it is not strong enough evidence on its own. Furthermore, the wide range of time intervals between vaccination and the onset of GBS symptoms, ranging from 1 to 60 days, suggests that the relationship between the two is complex and involves multiple factors. Only 3 patients had previous autoimmune conditions like rheumatic arthritis for which the person was taking medication before the development of GBS. Our findings align with previous reports that indicate a possible association between COVID-19 vaccines and GBS with unique clinical characteristics, such as severe quadriplegia, frequent bilateral facial palsy, or atypical incomplete forms. Ongoing monitoring and additional research using rigorous methodologies are necessary to fully understand the significance of this association. Moreover, in patients with other autoimmune diseases, we were unable to determine if GBS was due to an autoimmune disease or the vaccination itself. The analysis is limited in comparing the clinical features of GBS after adenoviral vector vaccines with other vaccines. Third, the study included cases of patients after the administration of primary vaccine and the outcomes may not apply to booster shots.

Non commissioned, externally peer-reviewed.

There are no conflicts of interest.

Datasets generated during and/or analyzed during the current study are publicly available, available upon reasonable request.