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

ObjectiveTo investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination.BackgroundOn July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS.MethodsThe reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson’s chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths.ResultsThe reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7–1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis.ConclusionsAlthough the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.     

The risk of Guillain-Barré syndrome following infection with Campylobacter jejuni

To estimate the incidence of Guillain-Barré syndrome (GBS) following Campylobacter jejuni infection (CI) we studied three populations where outbreaks of CI had occurred involving an estimated 8000 cases. No case of GBS was detected in the 6 months following the outbreaks in the local populations. The point estimate for the risk of GBS following CI estimated in this study was 0 in 8000 (95% confidence interval 0-3).     

Risk of Guillain-Barré syndrome after 2010–2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.     

Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink

ObjectiveDescribe the Vaccine Safety Datalink’s (VSD) Guillain Barré Syndrome (GBS) surveillance following quadrivalent HPV vaccine (4vHPV) from 2006 through 2015.MethodsAmong 4vHPV vaccinated persons aged 9–26, ICD-9 coded GBS was identified in VSD’s electronic data. Medical records were reviewed and adjudicated to confirm GBS. We calculated incidence rates of confirmed GBS within 1–42 days following 4vHPV with a one-sided 95% confidence interval.ResultsFollowing 2,773,185 4vHPV doses, we confirmed 1 case of GBS in a male and no cases among females. The incidence rate of medical record confirmed GBS within 42 days following 4vHPV vaccine was 0.36 cases per million 4vHPV doses administered (1-sided 95% CI 1.71), which was less than the background rate.ConclusionWe found no evidence of an increased risk of GBS following 4vHPV. With an upper 95% confidence limit, we estimate that, if an increased risk exists, we would expect at most 1.08 additional cases of GBS per million people vaccinated with 4vHPV.     

Guillain-Barré syndrome and influenza vaccines: A meta-analysis

Cases of Guillain-Barré syndrome (GBS) have been occasionally associated with influenza vaccines; this possible risk, even if rare, is a matter of much concern. To investigate the strength of this association, a systematic review and a meta-analysis have been conducted; for the purpose, controlled observational studies addressing the risk of GBS associated with different influenza vaccines were sought. We finally selected 39 studies of interest published between 1981 and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both vaccines simultaneously administered, 1); funnel plot did not identify publication bias. At the association between any influenza vaccine – whether seasonal or pandemic – with GBS, the overall relative risk was 1.41 (95% CI, 1.20–1.66). Pandemic vaccines presented a higher risk (RR = 1.84; 95% CI, 1.36–2.50) compared to seasonal vaccines (RR = 1.22; 95% CI, 1.01–1.48); the latter should be considered as marginally statistically significant. Pandemic adjuvanted vaccines were not found to be related to a higher risk compared to non-adjuvanted vaccines. The results of the present meta-analysis point to a small but statistically significant association between influenza vaccines, particularly the pandemic ones, and GBS, which is consistent with current explanations upon possible mechanisms for this condition to appear.     

Guillain-Barré syndrome and H1N1 (2009) pandemic influenza vaccination using an AS03 adjuvanted vaccine in the United Kingdom: self-controlled case series

In 1976 a swine influenza vaccine was associated with an increased risk of Guillain-Barré syndrome (GBS). Although subsequent studies did not find an increased risk of GBS following seasonal influenza vaccine, there was concern that the monovalent H1N1 vaccines developed against the swine influenza pandemic of 2009 might increase the risk of GBS. In the UK a split-virion AS03 oil-in-water adjuvanted vaccine (Pandemrix™) was predominantly used. To determine whether the risk of GBS increased after Pandemrix administration, we sought GBS cases during the period of vaccine use from neurologists and a patient support group, and following the vaccination period from hospital episode statistics (HES) in England. We obtained cases’ vaccination histories and illness onset dates from general practitioners. We determined the relative incidence of GBS in the 6 weeks after vaccination using the self-controlled case series method on the cases identified in HES. We included 327 GBS cases, of whom 37 received pandemic vaccine in the study period, nine of whom developed GBS within 6 weeks of vaccination (relative incidence 1.05 [95% confidence interval (CI) 0.37 to 2.24]). We found no evidence of an increased risk of GBS in the 6 weeks following pandemic influenza vaccination.     

Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study

Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009–2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47 % of the population and the vaccination coverage was 39.25 %. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95 % confidence interval (CI) 1.08–1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95 % CI 1.17–20.36). After pandemic vaccination the adjusted HR was 1.11 (95 % CI 0.51–2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.     

Is caring associated with an increased risk of mortality? A longitudinal study

Informal care is a fundamental component of care in the community which, given current demographic trends and increasing prevalence of debilitating chronic disease, is likely to assume even greater significance in future. Research indicates that caregivers are more likely than non-carers to report poor health, though this has usually been measured in terms of psychological or emotional health such as depression or 'caregiver strain'. Relatively little is known about the effects of caring on physical health. This study examines the health of caregivers recorded in the 2001 Northern Ireland Census and their subsequent mortality over the following four years. Caregivers were a heterogeneous group, with those providing fewer hours of care being relatively more affluent than those providing care at greater intensities. Overall, caregivers had lower mortality risks than non-carers and effects were more pronounced for women, older people, and for those reporting poorer health at the start of the study period. While this study does not exclude the possibility of significant detrimental health effects of caring for some sub-groups of caregivers, it does add support to the growing body of literature which suggests that the positive aspects of caring have been underreported.     

Parents’ and guardians’ views on the acceptability of a future COVID-19 vaccine: A multi-methods study in England

BackgroundThe availability of a COVID-19 vaccine has been heralded as key to controlling the COVID-19 pandemic. COVID-19 vaccination programme success will rely on public willingness to be vaccinated.MethodsWe used a multi-methods approach - involving an online cross-sectional survey and semi-structured interviews - to investigate parents’ and guardians’ views on the acceptability of a future COVID-19 vaccine. 1252 parents and guardians (aged 16 + years) who reported living in England with a child aged 18 months or under completed the survey. Nineteen survey participants were interviewed.FindingsMost survey participants reported they would likely accept a COVID-19 vaccine for themselves (Definitely 55.8%; Unsure but leaning towards yes 34.3%) and their child/children (Definitely 48.2%; Unsure but leaning towards yes 40.9%). Less than 4% of survey participants reported that they would definitely not accept a COVID-19 vaccine. Survey participants were more likely to accept a COVID-19 vaccine for themselves than their child/children. Participants that self-reported as Black, Asian, Chinese, Mixed or Other ethnicity were almost 3 times more likely to reject a COVID-19 vaccine for themselves and their children than White British, White Irish and White Other participants. Survey participants from lower-income households were also more likely to reject a COVID-19 vaccine. In open-text survey responses and interviews, self-protection from COVID-19 was reported as the main reason for vaccine acceptance. Common concerns identified in open-text responses and interviews were around COVID-19 vaccine safety and effectiveness, mostly prompted by the newness and rapid development of the vaccine.ConclusionInformation on how COVID-19 vaccines are developed and tested, including their safety and efficacy, must be communicated clearly to the public. To prevent inequalities in uptake, it is crucial to understand and address factors that may affect COVID-19 vaccine acceptability in ethnic minority and lower-income groups who are disproportionately affected by COVID-19.     

Rapidly developing weakness mimicking Guillain-Barré syndrome in beriberi neuropathy: two case reports

OBJECTIVE: We examined the diagnostic difficulty in thiamine deficiency. METHODS: We report on two patients with polyneuropathy associated with thiamine deficiency (i.e., beriberi neuropathy) that presented with acute motor symptoms mimicking Guillain-Barré syndrome. RESULTS: The cause of the thiamine deficiency was associated with gastrectomy to treat cancer in a 46-y-old man and with dietary imbalance in a 33-y-old man. The thiamine deficiency was not related to alcohol intake in either patient. In both patients, the upper and lower extremities showed a rapidly progressive weakness over the course of 1 mo. Muscle weakness in the first patient progressed even after admission to the hospital, and urinary retention, Wernicke's encephalopathy, lactic acidosis, paralytic ileus, and heart failure appeared subsequently. Clinical symptoms in both patients showed improvement after initiation of thiamine administration, although some residual deficit remained. CONCLUSION: Thiamine deficiency must be actively considered as a possible cause of polyneuropathy, and variability in its clinical features should be taken into consideration.     

Irritable bowel syndrome correlates with increased risk of Parkinson’s disease in Taiwan

This study investigated whether an association exists between irritable bowel syndrome (IBS) and the risk of Parkinson’s disease. This is a retrospective cohort study using the dataset of the Taiwan National Health Insurance Program from 2000 to 2010. We identified 23,875 patients (aged 20 years or older) with newly diagnosed IBS as the IBS group and 95,500 subjects without IBS as the non-IBS group for comparison. The main outcome was incident Parkinson’s disease compared between both groups by the end of 2010. We measured the hazard ratio (HR) to evaluate the association between IBS and Parkinson’s disease. The overall incidence of Parkinson’s disease in the IBS group was 1.76-fold higher than that in the non-IBS group (16.4 vs. 9.33 per 10,000 person-years). The multivariable Cox proportional hazards regression analysis revealed that the adjusted HR of Parkinson’s disease associated with IBS was 1.48 (95 % CI 1.27, 1.72), compared with the non-IBS group. Age, women, hypertension, dementia, cerebrovascular disease and depression were also significantly associated with Parkinson’s disease. Patients with irritable bowel syndrome are at an increased risk of developing Parkinson’s disease. Further studies are required to explore the pathophysiological connection between these disorders.     

Assurance of neuroattenuation of a live vaccine against West Nile virus: A comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine

The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4Δ30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4Δ30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4Δ30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4Δ30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Δ30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4Δ30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4Δ30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4Δ30 and DEN4Δ30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches.     

Guillain-Barré syndrome following receipt of influenza A (H1N1) 2009 monovalent vaccine in Korea with an emphasis on Brighton Collaboration case definition

Background

In 2009-2010 season, with ongoing of influenza A (H1N1), employment of mass vaccination has generated concerns in issue of adverse events following immunization (AEFI). This study investigates the clinical and laboratory data of reported cases of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) following receipt of influenza A (H1N1) 2009 monovalent vaccine to the National Vaccine Injury Compensation Program (NVICP) in Korea, with all cases reviewed under case definition developed by Brighton Collaboration GBS Working Group.

Method

Retrospective review of medical records for all suspected cases of GBS ad FS following receipt of influenza A (H1N1) monovalent vaccine reported to NVICP from December 1, 2009, through April 28, 2010 was conducted. Additional analyses were performed for identification of levels of diagnostic certainty according to Brighton Collaboration case definition.

Result

Of 29 reported cases, 22 were confirmed to meet Brighton criteria level 1, 2, or 3 for GBS (21) or FS (1). Of those, 2 (9.1%) met level 1, 9 (40.9%) met level 2, and 11 (50.0%) met level 3. The male to female ratio was 2:0 in cases with level 1, 8:1 in cases with level 2, and 3:8 in cases with level 3. The mean age was older in cases with level 1 (54.0 ± 26.9) than that of cases with level 2 (25.6 ± 22.8), and level 3 (13.6 ± 2.4, P = 0.005). The median onset interval was longer in cases with level 1 (16 days) than that of cases that met level 2 (12.44 days), and 3 (1.09 days, P = 0.019).

Conclusion

The Brighton case definition was used to improve the quality of AEFI data in Korea, and was applicable in retrospective review of medical records in cases with GBS and FS after influenza A (H1N1) vaccination. These findings suggest that standardized case definition was feasible in clarifying the AEFI data, and to further increase the understanding of possible relationship of influenza vaccine and GBS.     

The risk of non-specific hospitalised infections following MMR vaccination given with and without inactivated vaccines in the second year of life. Comparative self–controlled case-series study in England

Observational cohort studies in high-income settings have suggested that vaccination order may affect children’s subsequent risk of a heterologous infection, with live vaccines reducing and inactivated vaccines (given on their own or with a live vaccine), increasing the risk. We used the self-controlled case-series method, which automatically controls for the individual level confounding to which such cohort studies are prone, to test this hypothesis. We compared the relative incidence (RI) of infections post-vaccination in two calendar periods in England; in Period 1 (September 2002–August 2006) live measles, mumps, rubella (MMR) vaccine was given on its own and in Period 2 (September 2006–April 2010) inactivated vaccines (7-valent pneumococcal conjugate vaccine (PCV7) and sometimes the combined Haemophilus influenzae type b/meningococcal group C vaccine (Hib-MenC)) were given concomitantly with MMR. Admissions for an infection of the upper or lower respiratory tract, gastrointestinal system or other site in children aged 11–23 months were selected from the Hospital Episode Statistics database in England and linked to child health immunisation histories. The analysis included a total of 24,144 infections in 21,067 children in Period 1 and 36,880 in 31,616 children in Period 2. The RI of admission for any infection in Period 1 was 1.00 (95% confidence interval 0.95–1.06) compared with 0.95 (95% confidence interval 0.90–1.00) in Period 2. Comparing the two periods showed no evidence of a difference in the relative incidence estimates with a ratio of RI of 0.94 (95% confidence interval 0.87–1.02), RIs within 90 days of vaccination were 0.94 (0.91–0.97) in Period 1 and 0.94 (0.91–0.97) in Period 2, consistent with a temporary healthy vaccinee effect. In conclusion, we found no evidence to support the hypothesis that there is a reduction in heterologous infections after MMR on its own or an increase after MMR given concomitantly with an inactivated vaccine.