COVID-19 vaccine safety: Background incidence rates of anaphylaxis, myocarditis, pericarditis, Guillain-Barré Syndrome, and mortality in South Korea using a nationwide population-based cohort study.

BACKGROUND: To properly assess an association between vaccines and specific adverse events requires a comparison between the observed and background rates; however, studies in South Korea are currently limited. Therefore, in this study, we estimated the background incidence of anaphylaxis, myocarditis, pericarditis, Guillain-Barré syndrome (GBS), and mortality in South Korea. METHODS: A retrospective cohort study was conducted using the National Sample Cohort (NSC) data. Using NSC, the background incidence rate was estimated by dividing the number of episodes during 2009-2019 by the total population by year and then multiplying by 100,000. Using Statistics Korea data, the background mortality rate was estimated by dividing the number of deaths, during 2009-2019 by the standard population for that year and then multiplying by 100,000. Using background mortality rates, we predicted mortality rates for 2021 using autoregressive integrated moving average models. Further, the expected mortality rates were compared with observed mortality rates. RESULTS: The age-adjusted incidence rate (AIR) of anaphylaxis increased from 4.28 to 22.90 cases per 100,000 population (p = 0.003); myocarditis showed no significant increase, changing from 0.56 to 1.26 cases per 100,000 population (p = 0.276); pericarditis increased from 0.94 to 1.88 cases per 100,000 population (p = 0.005); and GBS increased from 0.78 to 1.21 cases per 100,000 population (p = 0.013). The age-adjusted mortality rate decreased from 645.24 to 475.70 deaths per 100,000 population (p <0.001). The 2021 observed/expected mortality rates for overall (ratio: 1.08, 95% confidence interval [CI]: 1.07-1.08), men (ratio: 1.07, 95% CI: 1.07-1.08), and women (ratio: 1.08, 95% CI: 1.07-1.09), were all significantly higher. When stratified by age group, those aged ≥80 (ratio: 1.16, 95% CI: 1.15-1.17), 60-69 (ratio: 1.11, 95% CI: 1.10-1.13), and 20-29 years old (ratio: 1.07, 95% CI: 1.02-1.13) were also significantly higher. CONCLUSION: Through the estimation of background rates related to anaphylaxis, myocarditis, pericarditis, GBS, and mortality, we established a reference point for evaluating the potential excess occurrence of adverse events following COVID-19 vaccination. This reference point serves as substantive evidence supporting the safety profile of COVID-19 vaccines.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Immune thrombocytopenic purpura and Guillain-Barré syndrome after 23-valent pneumococcal polysaccharide vaccination in Japan: The vaccine effectiveness, networking, and universal safety (VENUS) study.

BACKGROUND: To address the lack of an active vaccine safety surveillance system in Japan, the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study was initiated in 2021 as a pilot system using existing health insurance claims data and vaccination records. METHODS: This study evaluated the value of the VENUS study by assessing the incidence of immune thrombocytopenic purpura (ITP) and Guillain-Barré syndrome (GBS) following vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) using a self-controlled case series (SCCS) design. RESULTS: Incidence rate ratios for ITP during 28-day and 42-day risk periods were 0.89 (95% confidence interval [CI], 0.12-6.4), and 0.58 (95% CI, 0.081-4.2), respectively. Neither was statistically significant. Incidence rate ratios could not be estimated for GBS due to the limited sample size. CONCLUSION: The VENUS study can provide valuable insights to facilitate the establishment of an advanced vaccine monitoring system in Japan.

Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms.

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a "double-edged sword" as the use of ICIs caused multiple immune-related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function-related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI-induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy.

Guillain Barré syndrome after combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine: A rare pediatric case report and review of literature.

A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl's GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.

How to distinguish Guillain-Barré syndrome from nitrous oxide-induced neuropathy: A 2-year, multicentric, retrospective study.

BACKGROUND: Recreational use of nitrous oxide (N2 O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide-induced neuropathy (N2 On). Challenging clinical features can mimic Guillain-Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined. METHODS: Fifty-eight N2 On patients from three referral centers were retrospectively included over a 2-year period and compared to GBS patients hospitalized during the same timeframe (47 patients). Collected demographic, clinical, biological, and electrophysiological data were compared between the two groups. RESULTS: The typical N2 On clinical pattern included distal sensorimotor deficit in lower limbs with absent reflexes, proprioceptive ataxia, and no cranial involvement (56.7% of our cohort). Misleading GBS-like presentations were found in 14 N2 On patients (24.1%), and 13 patients (22.4%) did not report N2 O use during initial interview. Only half the N2 On patients presented with reduced vitamin B12 serum levels upon admission. A slightly increased cut-off (<200 pmol/L) demonstrated 85.1% sensitivity and 84.5% specificity in distinguishing N2 On from GBS. Only 6.9% of N2 On patients met the criteria for primary demyelination (p < 0.01), with only one presenting conduction blocks. A diagnostic algorithm combining these two biomarkers successfully classified all GBS-like N2 On patients. CONCLUSIONS: Vitamin B12 serum level < 200 pmol/L cut-off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2 On from GBS patients. These two parameters are particularly useful in clinically atypical N2 On with GBS-like presentation.

Case Report: ICIs-induced Guillain-Barré syndrome recovered from mycophenolate mofetil.

The emergence of immune checkpoint inhibitors (ICIs) has significantly prolonged the survival time of cancer patients. However, it may also lead to various immune-related adverse events (irAEs), including Guillain-Barré syndrome (GBS), a rare type of irAE. Most GBS patients can recover spontaneously due to the self-limited nature of the disease, but severe cases can result in respiratory failure or even death. Here we report a rare case of GBS occurring in a 58-year-old male patient with non-small cell lung cancer (NSCLC) who developed muscle weakness and numbness of the extremities during chemotherapy combined with KN046, a PD-L1/CTLA-4 bispecific antibody. Despite receiving methylprednisolone and γ-globulin, the patient's symptoms did not improve. However, there was significant improvement after treatment with mycophenolate mofetil (MM) capsules, which is not a routine regimen for GBS. To the best of our knowledge, this is the first reported case of ICIs-induced GBS that responded well to mycophenolate mofetil instead of methylprednisolone or γ-globulin. Thus, it provides a new treatment option for patients with ICIs-induced GBS.

Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years.

Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.

Neurological sequelae of vaccines.

IMPORTANCE: Vaccines are a safe and efficacious way to prevent a variety of infectious diseases. Over the course of their existence, vaccines have prevented immeasurable morbidity and mortality in humans. Typical symptoms of systemic immune activation are common after vaccines and may include local soreness, myalgias, nausea, and malaise. In the vast majority of cases, the severity of the infectious disease outweighs the risk of mild adverse reactions to vaccines. Rarely, vaccines may be associated with neurological sequela that ranges in severity from headache to transverse myelitis, acute disseminated encephalomyelitis, and Guillain-Barre syndrome (GBS). Often, a causal link cannot be confirmed, and it remains unclear if disease onset is directly related to a recent vaccination. OBSERVATIONS: This review serves to summarize reported neurologic sequelae of commonly used vaccines. It will also serve to discuss potential pathogenesis. It is important to note that many adverse events or reactions to vaccines are self-reported into databases, and causal proof cannot be obtained. CONCLUSIONS AND RELEVANCE: Recognition of reported adverse effects of vaccines plays an important role in public health and education. Early identification of these symptoms can allow for rapid diagnosis and potential treatment. Vaccines are a safe option for prevention of infectious diseases.

COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database.

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS), and an association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals to investigate the relationship between COVID-19 vaccination and GBS. Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. Nine hundred and ninety-six GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. One hundred and ninety-eight GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England [0.618 cases per 100,000 vaccinations; 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer) and one mRNA-1273 (Moderna)]. The 6-week excess of GBS (compared to the baseline rate of GBS cases 6-12 weeks after vaccination) occurred with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January-July 2021 was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe. Analysis of the linked NID/NIMS dataset suggested that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95% confidence interval 0.481-0.691) cases per 100 000 doses. However, examination of a multicentre surveillance dataset suggested that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.

Recombinant protein subunit COVID-19 vaccine-induced Guillain-Barré Syndrome in an adolescent: A case report.

Guillain-Barré Syndrome (GBS), an autoimmune neurological disease of peripheral nerves, has been causally associated with COVID-19 vaccination in adults. However, no such report has been published so far in children. We describe a 13-year-old female child who presented to the emergency department with complaints of bilateral upper limb, lower limb and truncal weakness over 3 days following first dose of recombinant protein subunit COVID-19 vaccine (Corbevax). Clinical examination and nerve conduction studies showed pure motor axonal polyneuropathy with absent compound muscle action potential (CMAP) in all sampled nerves of upper and lower limbs which was consistent with the diagnosis of GBS after ruling out possible alternative aetiologies. A temporal association between first dose of protein subunit COVID-19 vaccine administered a day prior and symptom onset was noted. The causality assessment using the World Health Organization (WHO) tool for adverse event following immunization (AEFI) assessment indicated vaccine product-related reaction categorized as A1. The patient's clinical condition improved after seven sessions of plasmapheresis. The purpose of this report is to create awareness among health care professionals about COVID-19 vaccine-induced GBS in children as early diagnosis and management can be critical in avoiding complications and improving patient outcomes.

Guillain-Barré syndrome temporally associated with COVID-19 vaccines in Victoria, Australia.

Guillain-Barré syndrome (GBS) is an adverse event of special interest (AESI) for surveillance systems monitoring adverse events following immunisation (AEFI) with COVID-19 vaccines. Emerging data support a temporal association between GBS and adenovirus-vector COVID-19 vaccines. We present a case series of GBS reports submitted between February and November 2021 to our enhanced spontaneous surveillance system (SAEFVIC) in Victoria, Australia, following vaccination with either the adenovirus-vector vaccine Vaxzevria ChadOx1-S (AstraZeneca) or an mRNA vaccine (Comirnaty BNT162b2 [Pfizer-BioNTech] or Spikevax mRNA-1273 [Moderna]). For each report, Brighton Collaboration case definitions were used to describe diagnostic certainty. Severity was graded using the GBS Disability Score. The observed incidence of GBS following immunisation against COVID-19 was compared to expected background ICD10-AM G61.0 coded hospitalisations. There were 41 total cases of GBS reported to SAEFVIC following Vaxzevria (n = 38), Comirnaty (n = 3), or Spikevax (n = 0) vaccines. The observed GBS incidence rate exceeded the expected background rate for Vaxzevria only, with 1.85 reports per 100,000 doses following dose 1, higher than the expected rate of 0.39 hospital admissions per 100,000 adults within 42 days of vaccination. Of 38 GBS reports following Vaxzevria, the median age at vaccination was 66 years and median onset of symptoms was 14 days following immunisation. There was one death. Four cases initially categorised as GBS were later reclassified as acute-onset chronic inflammatory demyelinating polyneuropathy. Fatigue was the predominant persisting symptom reported at follow up. Additional global studies are required to characterise risk factors, clinical variability, and to provide precision and generalizability regarding AEFI risks such as GBS associated with different vaccine platforms, which will help inform communication of the potential benefits and risks of COVID19 vaccination.

Miller-Fisher syndrome and Guillain-Barre syndrome overlap syndrome following inactivated COVID-19 vaccine: Case report and scope review.

Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) manifesting as the triad of ataxia, areflexia, and ophthalmoplegia. With the extensive 2019 coronavirus disease (COVID-19) immunization program, cases of GBS or MFS following vaccination are increasingly being reported. A 64-y-old Chinese man presented with new-onset paresthesia of the extremities, bilateral abduction limitation, right facial palsy, areflexia of bilateral lower limbs, and left-dominant limb ataxia 12 d after the second dose of inactivated vaccine against COVID-19. Cerebrospinal fluid analysis indicated albumin-cytological dissociation and was positive for anti-GQ1b IgG and anti-GT1b IgG. Nerve conduction studies of limbs showed evidence of axonal neuropathy with reduced sensory amplitudes. Based on the clinical presentations, temporal progression of symptoms, and laboratory findings, the diagnosis of MFS-GBS overlap syndrome was made. The patient was treated with intravenous immunoglobulin and acupuncture and made a complete recovery 54 d after the onset of his initial neurological signs. To the best of our knowledge, we report the first case of MFS-GBS overlap syndrome following the inactivated COVID-19 vaccination. However, a coincidental relationship with this inactivated vaccine cannot be excluded. Although the benefits of COVID-19 vaccination largely outweigh its risk and the prognosis of MFS is generally favorable, a close surveillance of neurological complications post-COVID-19 vaccination is always necessary, considering its potentially disabling and lethal effects on vaccinated populations.

Guillain-Barré syndrome following influenza vaccination: A 15-year nationwide population-based case-control study.

BACKGROUND AND PURPOSE: Influenza vaccination may increase the risk of developing Guillain-Barré syndrome (GBS) due to an elicited immune response, but the exact magnitude and duration of risk is unclear and hence the aim of this study. METHODS: We conducted a retrospective nationwide population-based case-control study of prospectively collected data on all patients with first-time hospital-diagnosed GBS in Denmark between 2002 and 2016 and 10 age-, sex- and index date-matched population controls per case. The primary exposure was incident influenza vaccination 1 month prior to admission with GBS. We used medical registries to ascertain a complete hospital contact history of pre-existing morbidities. To examine duration of GBS risk, we repeated the analysis for five consecutive 1-month risk periods following vaccination. RESULTS: Of the 1295 GBS cases and 12,814 controls, 20 cases (1.5%) and 119 controls (0.9%) had received an influenza vaccination within the last month, yielding a comorbidity-adjusted odds ratio of 1.9 (95% confidence interval 1.1-3.2) for GBS. Stratified analyses by calendar time, gender and age showed similar results. The increased risk of GBS was largely confined to 1 month following influenza vaccination. The population-attributable fraction of GBS from influenza vaccination in Denmark was 0.4%. CONCLUSIONS: Influenza vaccination was associated with a slightly elevated risk of GBS occurrence within 1 month after vaccination. However, only 1.5% of GBS cases in Denmark are associated with recent influenza vaccination. Thus, the benefit of influenza vaccines in preventing influenza infections and associated morbidity and mortality needs to be weighed against the small absolute risk of GBS.

[Guillain Barre syndrome associated with coronavac vaccine. Report of one case]. / Reporte de un caso de Síndrome de Guillain Barré post vacuna Coronavac: ¿rol causal o asociación temporal?

We report a 50-year-old woman with a history of celiac disease, who presented with lumbar pain and progressive flaccid tetraparesis 48 hours after the inoculation of the first dose of CoronaVac inactivated SARS-CoV-2 vaccine. CSF was normal and electrodiagnostic studies showed an axonal motor polyneuropathy. No other triggers were identified, and other etiologies were ruled out. The presentation was compatible with the AMAN (Acute Motor Axonal Neuropathy) subtype of GBS, and intravenous immunoglobulin halted the progression of symptoms. Intensive neurorehabilitation was performed. The patient was discharged five weeks after admission, walking with poles and climbing stairs with minimal assistance. To date no cases of inactivated SARSCoV-2 vaccine related GBS have been reported. Thus, description of its clinical presentation is relevant. We discuss the current evidence relating GBS with vaccines, highlighting that vaccine associated GBS is a controversial entity and causality must be interpreted cautiously given the actual COVID-19 pandemic context.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

Guillain-Barré Syndrome Associated with COVID-19 Vaccines: A Perspective From Spontaneous Report Data.

BACKGROUND AND OBJECTIVE: The concern surrounding the association between Guillain-Barré syndrome (GBS) and vaccination has increased with the widespread use of COVID-19 vaccines. The aim of this study was to assess the potential association of GBS with mRNA-based or adenovirus-vectored COVID-19 vaccines. METHODS: Reports of GBS associated with mRNA-based or adenovirus-vectored COVID-19 vaccines were extracted from the WHO pharmacovigilance database, exposure data from the Our World in Data website, and the background rates of GBS from published data. For countries contributing to VigiBase and with available data on COVID-19 vaccine exposure, reporting rates were estimated and observed-to-expected (OE) analyses were performed. RESULTS: A total of 2499 cases were included: 1157 (46.3%) cases with adenovirus-vectored COVID-19 vaccines and 1342 (53.7%) with mRNA-based COVID-19 vaccines. The male-to-female sex ratio was 1.09 and the median (IQR) age was 57 (45-66) years. The reporting rates (95% CI) per 100,000 person-years within the 42-day window were 5.57 (5.13-6.03) for adenovirus-vectored COVID-19 vaccines and 1.39 (1.31-1.47) for mRNA-based COVID-19 vaccines, while the background incidence was 1.2-3.1 per 100,000 person-years. For mRNA-based COVID-19 vaccines, the OE ratio was <1 for both time windows in all European countries and slightly elevated for the 21-day window in the USA. For adenovirus-vectored COVID-19 vaccines, the OE ratio was consistently > 2.0 for all countries. Sensitivity analyses minimally altered these results. CONCLUSIONS: These findings suggest both the absence of safety concern for GBS with mRNA-based COVID-19 vaccines and an increased risk with adenovirus-vectored COVID-19 vaccines. Back to top.