No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study

Case reports and series suggested an association between SARS-CoV-2 and Guillain-Barré syndrome (GBS). However, the GBS epidemic which was predicted from early risk estimates did not materialise in overall case numbers, and no plausible mechanism for any link has been established. An increased risk of GBS following adenoviral vector-based COVID-19 vaccination has been more consistently demonstrated, but a pathophysiological explanation for this association has also not yet emerged. Here, we sought to identify whether patients with GBS following COVID-19 infection or vaccination had any distinct clinical or serological features differentiating them from one another or non-pandemic GBS, and to explore the potential mechanisms of any associations. Between March 2020 and October 2021, sera from patients with GBS (n=64) and controls (n=70) were collected. Clinical features were retrieved from medical records. GBS cases were evaluated for diagnostic certainty by Brighton criteria and classified as non-COVID-19 associated (GBS-NC, n=20), GBS after COVID-19 infection (GBS-AC, n=10), or GBS after COVID-19 vaccination (GBS-AV, n=34). The humoral responses to SARS-CoV-2 proteins and putative peripheral nerve antigens, and the cytokine profile of each group were established and compared. Antibodies cloned from the acute-phase plasmablasts of an individual with GBS-AC were also assessed for reactivity against SARS-CoV-2 and peripheral nerve antigens. Sera from GBS patients and from individuals who received COVID-19 vaccinations (n=36: 16 ChAdOx1, 10 Ad26.COV2.S/Janssen, and 10 Tozinameran/Pfizer-BioNTech) without developing GBS were tested for IgG reactivity against SARS-CoV-2 and adenoviral proteins. There were no clinical differences between the GBS groups. Patients with GBS-AC had a greater IgG reactivity to the S1 component of the SARS-CoV-2 spike protein compared to non-GBS COVID-19 controls. A minority of antibodies from cloned plasmablasts targeted SARS-CoV-2 proteins but there was no reactivity or cross reactivity with peripheral nerve antigens or tissue. There were no other serological or immunological differences between the GBS groups. However, when compared to uncomplicated vaccine recipients, GBS patients in toto, and each group individually, demonstrated significantly greater antibody reaction to a range of human adenoviral proteins. Compared to controls exposed to the same immunological stimulus, antibody reactivities to viral antigens are enhanced in patients with GBS. However, we found no mechanistic link between S1 and peripheral nerve reactivity or pathology. Serological responses to adenoviral proteins may be directly involved in the pathogenesis of Guillain-Barré syndrome, potentially contributing to cases with currently unexplained aetiology.

Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine - United States, December 14-23, 2020.

Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine - United States, December 21, 2020-January 10, 2021.

Should women undergoing in vitro fertilization treatment or who are in the first trimester of pregnancy be vaccinated immediately against COVID-19

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.

Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in patients with an average age of 58. The average time for symptoms to appear was 14.4 days. Health care providers should be aware of this potential complication. Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. In this systematic study, we investigated at GBS cases that were reported after receiving the COVID-19 vaccination. Based on PRISMA guidelines, we searched five databases (PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases) for studies on COVID-19 vaccination and GBS on August 7, 2021. To conduct our analysis, we divided the GBS variants into two groups, acute inflammatory demyelinating polyneuropathy and non-acute inflammatory demyelinating polyneuropathy (AIDP and non-AIDP), and compared the two groups with mEGOS and other clinical presentation In this systematic review, 29 cases were included in 14 studies. Ten cases belonged to the AIDP variant, 17 were non-AIDP (one case had the MFS variant, one AMAN variant, and 15 cases had the BFP variant), and the two remaining cases were not mentioned. Following COVID-19 vaccination, GBS cases were, on average, 58 years of age. The average time it took for GBS symptoms to appear was 14.4 days. About 56 percent of the cases (56%) were classified as Brighton Level 1 or 2, which defines the highest level of diagnostic certainty for patients with GBS. This systematic review reports 29 cases of GBS following COVID-19 vaccination, particularly those following the AstraZeneca/Oxford vaccine. Further research is needed to assess all COVID-19 vaccines' side effects, including GBS.

Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, which causes acute flaccid paralysis. Most cases of GBS report either a gastrointestinal or respiratory tract infection in the 3–4 weeks preceding symptom onset. Molecular mimicry between the lipopolysaccharides of the infectious organism and the glycosphingolipids or similar nerve antigens in our body triggers the immune response.[1] Martic, et al. have presented an original study on the GBS followed by coronavirus disease 2019 (COVID-19) infection, vaccination, and other precipitating factors during the pandemic in Serbia and Montenegro.[2] They retrospectively recruited 109 GBS patients between January and April 2022 into the following three groups: COVID-19 infection-associated (19 cases), COVID-19 vaccination-associated (16 cases), and other causes (74 cases). Individuals positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on polymerase chain reaction (PCR) testing were classified as COVID-19-positive. A COVID-19 infection or vaccination was considered a trigger if it occurred between 3 days and 6 weeks before symptom onset. No differences were noted in the clinical presentation, electrophysiology, or outcome between the three groups of GBS patients. Demyelinating neuropathy was the most common electrophysiological subtype, the most common vaccine associated was Sinopharm (8/16 cases), and most events occurred after the first dose. Unlike the Zika virus pandemic, epidemiological studies have not demonstrated COVID-19 infection to be associated with GBS.[3,4] Experts have argued that an increase in GBS incidence might be masked by a decrease in GBS incidence due to other infectious triggers because of better hygiene, lockdown, and social distancing.[5] Studies from Japan and Brazil have reported a decreased incidence of infectious diseases during the lockdown because of these containment measures,[6,7] thereby indirectly reducing the occurrence of GBS. The “GBS consortium,” established in India with 26 centers,[5] found a reduction in the number of GBS cases during the COVID-19 pandemic compared with the same duration in the previous year in both adult[5] and pediatric groups.[8] Similar findings were reported by an epidemiological study conducted in the United Kingdom.[3] These studies[3,5] also reported no significant differences between GBS patients triggered by COVID-19 and those without the infection. Demyelinating GBS is the most common subtype worldwide and was unsurprisingly the most common in this study as well. Older age was associated with a worse prognosis. This was also expected as increasing age is associated with worse GBS outcomes. The relative rarity of COVID-19 vaccine-induced GBS was also in accordance with global data. The authors reported 16 cases of COVID-19 vaccine-induced GBS in the background of 54.1% coverage in adults in a population of 7,806,891 people.[2] The first dose of vaccines was the most common dose implicated, with Sinopharm use associated with most cases. AstraZeneca and Covaxin were the vaccines most commonly used in India, and very few vaccine-associated GBS cases have been reported.[9] A study from Kerala showed a mildly raised incidence of GBS associated with ChAdOx1-S/nCoV-19 vaccination.[10] A retrospective study conducted in the West and North Midlands of the United Kingdom between January and June 2021 reported only 12 cases of COVID-19 vaccine-induced GBS.[11] Most of these individuals had received AstraZeneca vaccines. They reported a higher likelihood of cranial nerve involvement in such GBS cases, similar to Martic, et al.[2] It should be added that this GBS occurrence post-vaccination does not necessarily prove causation. Temporal associations do not imply causality. Also, the COVID-19 vaccine benefits far outweigh the risk of such rare side effects. Finally, the authors mention that the patients were treated with intravenous immunoglobulin (IVIg) and plasma exchange in the standard way. In our experience during the pandemic, the proportion of GBS patients receiving IVIg was significantly higher than that of those receiving plasma exchange (PLEX).[5] The reasons were probably manifold: logistical (greater physician and nursing workforce were working in COVID-19 designated facilities) and difficulty in conducting plasma exchanges within COVID-19 facilities and patient choice (considering they were without accompanying family members in the hospital). The pandemic has shown the need for high-quality prospective longitudinal studies on Guillain–Barré syndrome in low- to middle-income countries. The International Guillain–Barré Syndrome Outcome Study (IGOS) and the recently established GBS consortium in India are good models for replicating in other parts of the world.

Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy related to infection with bacteria or virus and vaccination. Cases of GBS after coronavirus infection-19 (COVID-19) vaccination have been reported. However, cases of GBS after inoculation with mRNA-based COVID-19 vaccines, especially mRNA-1273, have rarely been reported compared to after inoculation with adenovirus vector-based COVID-19 vaccines. On 1 hand, GBS occurring after scrub typhus is often reported, but the exact pathological mechanism has not been elucidated. We report the case of a patient with GBS after inoculation with mRNA-1273 COVID-19 vaccine and scrub typhus. A 47-year-old man received COVID-19 vaccination 4 weeks before admission. He had a fever, rash and general weakness 1 day after vaccination. After 3 weeks, the muscle strength of the extremities deteriorated to the extent that walking was impossible. The patient developed quadriplegia with areflexia, axonal-type sensorimotor polyneuropathy was confirmed by nerve conduction study. The patient was diagnosed as GBS. Scrub typhus was also diagnosed as eschar was observed in the chest area and the serologic test of anti-R-tsutsugamushi antibody showed a strongly positive result. The patient received treatment with intravenous immunoglobulin at 0.4 g/kg daily for 5 days. Mechanical ventilation was applied during the intensive care unit. He was treated for scrub typhus simultaneously. Six months after the onset of the disease, the patient showed improvement to the point where he could work and exercise alone. When GBS is suspected, early evaluation and treatment can lead to favorable outcomes. Considering that cases of GBS after COVID-19 vaccination have been reported, it is important to conduct early evaluation and management of patients with muscle weakness after COVID-19 vaccination to ensure early detection of GBS. And even if fever and rash are side effects that can occur frequently after vaccination, it is necessary to consider other diseases in addition to the side effects of the vaccine. This is to prevent delay in diagnosis and treatment of other diseases.

Coronavirus Disease 2019 and Vaccination of Children and Adolescents: Prospects and Challenges

BackgroundThis study assessed and compared the frequency and type of adverse events (AEs) of the Pfizer-BioNTech, Moderna, and Janssen coronavirus disease 2019 (COVID-19) vaccines reported in the Vaccine Adverse Event Reporting System (VAERS).MethodsA retrospective analysis examined VAERS reports between 14 December 2020 and 8 October 2021 and focused on AE reports related to COVID-19 vaccines and AE outcomes [e.g., emergency room (ER) visits after being vaccinated, hospitalization, prolongation of existing hospitalization, life-threatening events, disability, birth defect, and death]. Reporting odds ratios (RORs) and Breslow-Day statistics were used to compare AE reporting between COVID-19 and non-COVID vaccines and between individual COVID-19 vaccines.ResultsA total of 604,157 AEs of COVID-19 vaccines were reported, including 43.51% for the Pfizer-BioNTech vaccine, 47.13% for the Moderna vaccine, and 9.12% for the Janssen COVID-19 vaccine. About 12.56% of patients visited ER after being vaccinated, 5.96% reported hospitalization, and 1.52% reported life-threatening events. Among the number of death cases (n = 7,674; mean age = 73), 2,025 patients (26.39%) had hypertension and 1,237 (16.12%) patients had cancer. RORs between COVID-19 vaccines and non-COVID vaccines identified increased ROR in ER visits, hospitalization, and life-threatening events. The results of the Breslow-Day statistics indicated heterogeneities between the disproportionality of reports across the four serious AE outcomes (i.e., ER visits, hospitalization, life-threatening events, and disability) between individual COVID-19 vaccines.ConclusionMost current VAERS reports showed that the most commonly reported AEs of COVID-19 vaccines were mild. Cases with a mortality outcome tended to occur in older adults with underneath conditions. Close ongoing surveillance in the safety of COVID-19 vaccines is critical and will inform the use of individual COVID-19 vaccines. Given the known limitations associated with the passive spontaneous reporting system, such as VAERS, our findings need to be further assessed and verified through longitudinal, large healthcare data systems.

Existing data regarding occurrence of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) infection and vaccination are inconclusive. We aimed to assess the association between GBS and both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccine. We conducted a nested case-control study in a cohort of 3,193,951 patients aged 16 years or older, without a diagnosis of prior GBS, from the largest health care provider in Israel. Participants were followed from January 1, 2021, until June 30, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls. Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine) and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the odds ratio for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration was ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks. Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, whereas Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.

Vaccination

The COVID-19 Pandemic in 2021: Avoiding Overdiagnosis of Anaphylaxis Risk While Safely Vaccinating the World

To investigate the association of optic neuritis (ON) after the COVID-19 vaccines. Cases of ON from Vaccine Adverse Event Reporting System (VAERS) were collected and divided into the prepandemic, COVID-19 pandemic, and COVID-19 vaccine periods. Reporting rates were calculated based on estimates of vaccines administered. Proportion tests and Pearson χ 2 test were used to determine significant differences in reporting rates of ON after vaccines within the 3 periods. Kruskal-Wallis testing with Bonferroni-corrected post hoc analysis and multivariable binary logistic regression was used to determine significant case factors such as age, sex, concurrent multiple sclerosis (MS) and vaccine manufacturer in predicting a worse outcome defined as permanent disability, emergency room (ER) or doctor visits, and hospitalizations. A significant increase in the reporting rate of ON after COVID-19 vaccination compared with influenza vaccination and all other vaccinations (18.6 vs 0.2 vs 0.4 per 10 million, P < 0.0001) was observed. However, the reporting rate was within the incidence range of ON in the general population. Using self-controlled and case-centered analyses, there was a significant difference in the reporting rate of ON after COVID-19 vaccination between the risk period and control period ( P < 0.0001). Multivariable binary regression with adjustment for confounding variables demonstrated that only male sex was significantly associated with permanent disability. Some cases of ON may be temporally associated with the COVID-19 vaccines; however, there is no significant increase in the reporting rate compared with the incidence. Limitations of this study include those inherent to any passive surveillance system. Controlled studies are needed to establish a clear causal relationship.