Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

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.

Guillain-Barré syndrome after COVID-19 vaccination: A systematic review and analysis of case reports.

INTRODUCTION: Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. Our work aims to investigate the incidence of GBS after COVID-19 vaccination, and describe its clinical characteristics and potential confounders. METHODS: An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports and case series describing after COVID-19 vaccine administration. All published articles from inception until November 1st, 2022 were included. Differences between groups were assessed using Pearson chi-square test. Modified Erasmus GBS Outcome Score (mEGOS) for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS. RESULTS: About 103 studies describing 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ±18.83 years, with AMSAN occurring in a rather older group (63.88 ±20.87 years, p=0.049). The AstraZeneca vaccine was associated with AIDP (n=38, 21.71%) more than other vaccines, p=0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Dysesthesias was the most reported sensory complication (60%, p=0.349). Most GBS patients survived (96%, p=0.036), however, most patients had low mEGOS scores (4 ±3.57, p<0.01). On average, patients developed GBS at 13.43 ±11.45 days from vaccination (p=0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p<0.01). Intravenous immunoglobulins (p=0.03) along with rehabilitation (p=0.19) were the most commonly used treatment. CONCLUSION: This work investigates the incidence of Guillain-Barré Syndrome after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca or Pfizer vaccines, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines. No specific predisposing or prognostic factor was identified, and the relation between the COVID-19 vaccines and GBS remain unclear.

Guillain-Barré syndrome and COVID-19 vaccination: a systematic review and meta-analysis.

BACKGROUND: Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. METHODS: A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model. RESULTS: Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases. CONCLUSIONS: Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.

Neuromuscular diseases associated with COVID-19 vaccines: a systematic review and pooled analysis of 258 patients.

BACKGROUND: Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination. METHODS: We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies. RESULTS: A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based. CONCLUSION: COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.

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.

Effects of COVID-19 vaccine type on Guillain-Barré syndrome: Two cases and a literature review.

Guillain-Barré syndrome (GBS) is a rare but severe complication of COVID-19 vaccination. We report two cases of GBS following vaccination with the adenovirus vector vaccine ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca) and review the relevant literature. Relevant studies published between December 2020 and May 2022 including 881 patients with GBS were reviewed. GBS incidence and the need for mechanical ventilation were reported at a higher level among patients receiving Vaxzevria (n = 400). However, incidence cannot be accurately estimated from case reports. Thus, the true GBS rates following COVID-19 vaccination should be determined by population-based data.

Antecedent infections, recent developments and future directions in Guillain-Barré syndrome.

The Guillain-Barré syndrome is an autoimmune polyradiculoneuropathy causing symmetrical weakness of limbs. After poliomyelitis, it is the second most common cause of paralysis, with an annual incidence of 0.84-1.91 per 100,000 individuals. The syndrome affects both men and women, showing a male preponderance. Campylobacter jejuni, epstein-barr virus, cytomegalovirus, mycoplasma pneumoniae and haemophilus influenzae are amongst the most common causative agents of Guillain-Barré syndrome. Several immunological and genetic factors have been recognised as the risk factors. Human leukocyte antigen, cluster of differentiation 1, and tumour necrosis factor-alpha alleles are among the frequently investigated loci in Guillain-Barré syndrome. Genome-wide association studies have found no significant association of Guillain-Barré syndrome with common variants. Many vaccines against Campylobacter jejuni infection have been proposed, but there are concerns about the efficacy and safety of these vaccines. So far, there is no approved vaccine against Campylobacter jejuni.

Neurological Complications Following COVID-19 Vaccination.

PURPOSE OF REVIEW: A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest. RECENT FINDINGS: There is a greater than expected occurrence of severe neurological adverse events such as cortical sinus venous thrombosis, Bell's palsy, transverse myelitis, and Guillain-Barré syndromes along with other common effects such as headaches following different kinds of COVID-19 vaccination. Precipitation of new onset demyelinating brain lesions with or without detection of specific antibodies and worsening of pre-existing neurological disorders (like epilepsy, multiple sclerosis) are also a matter of great concern though no conclusive evidence implicating the vaccines is available as of now. The COVID-19 pandemic is far from being over. Till such time that a truly effective anti-viral drug is discovered, or an appropriate therapeutic strategy is developed, COVID-appropriate behavior and highly effective mass vaccination remain the only weapons in our armamentarium to fight this deadly disease. As often occurs with most therapeutic means for the treatment and prevention of any disease, vaccination against COVID-19 has its hazards. These range from the most trivial ones like fever, local pain and myalgias to several potentially serious cardiac and neurological complications. The latter group includes conditions like cerebral venous thrombosis (curiously often with thrombocytopenia), transverse myelitis and acute inflammatory demyelinating polyneuropathy amongst others. Fortunately, the number of reported patients with any of these serious complications is far too low for the total number of people vaccinated. Hence, the current evidence suggests that the benefits of vaccination far outweigh the risk of these events in majority of the patients. As of now, available evidence also does not recommend withholding vaccination in patients with pre-existing neurological disorders like epilepsy and MS, though adenoviral vaccines should be avoided in those with history of thrombotic events.

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.

Guillain-Barré syndrome in an era of global infections and 21st century vaccination.

PURPOSE OF REVIEW: Guillain-Barre syndrome is sometimes a severe and disabling postinfectious neuromuscular paralysis that is causally associated with a number of well defined infections, and occasionally with immunization. The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) pandemic and the worldwide immunization programme provoked fears of an epidemic of coronavirus disease 2019 (COVID-19) related disease. As we emerge from the pandemic this review summarises some of the huge volume of publications about Guillain-Barre syndrome (GBS), COVID-19 and immunisation against it. RECENT FINDINGS: In the early months of COVID-19, there were concerns of significant numbers of cases of GBS resulting from SARS-CoV-2 infection. Large epidemiological studies have provided reassurance that the association of GBS with COVID-19 is small or absent. Despite considerable efforts, plausible pathogenic mechanisms aligned with our understanding of GBS causation have not been identified. Reliable data from national surveillance of COVID-19 vaccinations have shown GBS to occur at about 5.8 cases per million first doses of adenovirus vectored COVID-19 vaccines, otherwise not distinguishable from incident naturally occurring cases. However, this risk is far outweighed by the protective benefits of vaccination in the at-risk older deciles of age. SUMMARY: With no obvious link of GBS to COVID-19 epitopes, in particular the spike (S-)protein, but a clearly demonstrable causation in some susceptible individuals from the global rollout of novel adenovirus vectored vaccine technologies, adenoviruses are of significant interest in the pathogenesis of GBS as well as vectors in their many expanding pharmaceutical applications.

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.

Old age and multiple comorbidity are associated with delayed diagnosis of Guillain-Barre syndrome.

To assess whether older age and presence of comorbidities were associated with a delayed diagnosis of Guillain-Barré syndrome (GBS). The medical records of 140 patients diagnosed with GBS at Severance Hospital from March 2011 to December 2020 were retrospectively reviewed. Comorbidity profiles were assessed using the Charlson comorbidity index (CCI). The age-adjusted CCI (ACCI) score was calculated, which further incorporated the effect of age. Patients were classified into the early diagnosis group (diagnosis duration ≤ 14 days) and late diagnosis group (diagnosis duration > 14 days). Clinical features and comorbidity profiles were compared between the two groups. The cumulative incidence of diagnosis was compared between the low and high ACCI groups. Age was significantly higher in the late diagnosis group (61.8 ± 15.0 years) than in the early diagnosis group (49.1 ± 18.4, p = 0.001). The CCI score was higher in the late diagnosis group (≥ 3 in 26.1%) than in the early diagnosis group (≥ 3 in 5.1%, p = 0.01). The ACCI score demonstrated a positive correlation with the diagnosis duration (ß = 1.636, p < 0.001), indicating that the diagnosis was delayed in patients with a higher ACCI score. The duration from onset to diagnosis was longer in the high ACCI group than in the low ACCI group (log-rank test, p < 0.001). The diagnosis duration was significantly longer, especially in patients with malignancy and cardiovascular diseases. Delayed diagnosis of GBS is associated with older age and multiple comorbidities. Diagnostic delay was significant in patients with malignancies and cardiovascular diseases. Early suspicion of GBS is required in these patients.

Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform.

INTRODUCTION: We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy. METHODS: With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4-42 days for GBS, 4-28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression. RESULTS: Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33-3·47) and Bell's palsy (N = 5,350; 1·39; 1·27-1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96-2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75-1·57), transverse myelitis (N = 109; 1·62; 0·86-3·03) or Bell's palsy (N = 3,609; 0·89; 0·76-1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32-2·42). CONCLUSIONS: COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.

SARS-CoV-2 and Guillain-Barré Syndrome: Lessons from Viral Infections.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. COVID-19 has a broad clinical spectrum from asymptomatic patients to multiorgan dysfunction and septic shock. Most of the common symptoms of COVID-19 are classified as respiratory disorders, but some reports show neurological involvements. During the COVID-19 pandemic, a case series of neurological complications, such as Guillain-Barré syndrome (GBS), were reported. GBS is a neuroimmune disorder with acute inflammatory radicular polyneuropathy in different parts of the peripheral nerve. Some studies have reported GBS as an inflammatory neuropathy related to various viral infections, such as cytomegalovirus (CMV), Epstein-Barr Virus (EBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, and Zika virus. There are some immunomodulation approaches for the management of GBS. Studies have evaluated the effects of the various therapeutic approaches, including intravenous immunoglobulin (IVIG), plasma exchange (PE), complement inhibitors, and corticosteroids to regulate overactivation of immune responses during GBS in experimental and clinical studies. In this regard, the possible association between GBS and SARS-CoV-2 infection during the outbreak of the current pandemic and also the mentioned therapeutic approaches were reviewed.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance.

BACKGROUND: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of 11 adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. METHODS: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bell's palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barré syndrome, transverse myelitis, acute myocardial infarction, and anaphylaxis during five pre-pandemic years (2015-2019) and 2020. RESULTS: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 191 for acute myocardial infarction, 43.9 for idiopathic thrombocytopenia, 28.8 for anaphylaxis, 27.8 for Bell's palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.7 for pericarditis, 2.9 for myocarditis, 2.0 for Kawasaki disease, 1.9 for Guillain-Barré syndrome, and 1.7 for transverse myelitis. Females had higher rates of acute disseminated encephalomyelitis, transverse myelitis and anaphylaxis while males had higher rates of myocarditis, pericarditis, and Guillain-Barré syndrome. Bell's palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12 to 59 years for myocarditis and ≥12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. CONCLUSIONS: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Outcomes of patients presenting with Guillain-Barre Syndrome at a tertiary care center in India.

BACKGROUND: The Guillain-Barre Syndrome (GBS), also known as acute idiopathic polyneuritis, is a critical acquired condition associated with preceding nonspecific infection or triggering factors like trauma, surgery, or vaccination. GBS is currently the most frequent cause of acute flaccid paralysis in India. This study evaluates the short-term and in-hospital outcomes in different subtypes of GBS. METHODS: A prospective observational study was conducted at V.S. Hospital, Ahmedabad, from September 2015 to December 2017. Patients above the age of 12 were included. Patients having other underlying neurological conditions, as well as immunodeficiency disorders, were excluded. The patients were classified into different subtypes of GBS, and functional outcomes were recorded on admission and discharge according to Hughes Scoring System. All statistical analyses were performed by using SPSS software. RESULTS: Out of 50 patients, 35 (70%) were males. The mean age was of 37.18 +/- 18.35 years. 25 (50%) patients had a preceding infection. 88% of patients presented with cranial nerve (CN) involvement had a Hughes Score of >/= 3 (p = 0.0087). They had less improvement of Hughes Score on discharge (0.13 +/- 0.04) as compared to the patients without cranial nerve involvement (0.38 +/- 0.08) (p = 0.008). Respiratory involvement was associated with a higher Hughes Score (p = 0.005) on admission. 85% of patients diagnosed with an axonal subtype of GBS had a Hughes Score of >/= 3 (p = 0.06) compared to 74% patients with demyelinating subtype. Axonal subtype required double period (11 +/- 2.34) to show improvement as compared to demyelinating subtype (6 +/- 1.2) (p = 0.020). Irrespective of the subtypes, in two different treatment cohorts (PLEX vs IVIG), there was no difference in short term functional outcomes measured by improvement in the Hughes scores (p = 0.89). CONCLUSIONS: Early cranial nerve and respiratory involvement in patients presenting with GBS are associated with poor outcomes warranting immediate critical care involvement. In our study, amongst all the subtypes, axonal had poor clinical outcomes. Further clinical trials on the Indian subpopulation will help us evaluate the impact of different treatment modalities on this disease.

Association Between Incident Cancer and Guillain-Barré Syndrome Development: A Nationwide Case-Control Study.

BACKGROUND AND OBJECTIVES: Cancer may increase the risk of developing Guillain-Barré syndrome (GBS) due to molecular mimicry or immunosuppression, but the exact relationship is unclear. We aimed to determine the association between incident cancer and the following risk of GBS development. METHODS: We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 1987 and 2016 and 10 age-, sex-, and index date-matched population controls per case. We identified incident cancer diagnoses between 6 months before and 2 months after the GBS index date. We used conditional logistic regression to compute odds ratios (ORs) as a measure of relative risk and performed stratified analyses to assess the impact of cancer on GBS risk in strata of calendar periods, sex, and age. In sensitivity analyses, to assess any potential risk of survival bias induced by including cancer diagnoses potentially made after GBS diagnosis, we examined incident cancers in both a broader exposure window (1 year before to 3 months after GBS index date) and a narrower window (6 months to 1 month before the GBS index date). RESULTS: Of the 2,414 patients with GBS and 23,909 controls included, 49 cases (2.0%) and 138 controls (0.6%) had a recent cancer diagnosis, yielding a matched OR of 3.6 (95% CI 2.6-5.1) for GBS associated with cancer. Stratification by calendar time, sex, and age showed robust results for the association between cancer and GBS, with no major variations. Broadening and narrowing the exposure window produced slightly weakened associations of OR of 2.4 (95% CI 1.8-3.3) and 2.5 (95% CI 1.5-4.1), respectively. The GBS ORs were highest for cancers of the lymphatic and hematopoietic tissue (OR 7.2, 95% CI 2.9-18.0), respiratory tract (OR 5.6, 95% CI 2.7-11.9), prostate and other male genital organ (OR 5.0, 95% CI 2.1-11.6), and breast (OR 5.0, 95% CI 1.7-14.5) cancer. DISCUSSION: In this large nationwide epidemiologic study, incident cancer was associated with a markedly increased risk of subsequent GBS development. The results suggest that as-yet unidentified factors present in several types of cancer drive this association.

Association between covid-19 vaccination, SARS-CoV-2 infection, and risk of immune mediated neurological events: population based cohort and self-controlled case series analysis.

OBJECTIVE: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events. DESIGN: Population based historical rate comparison study and self-controlled case series analysis. SETTING: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data. PARTICIPANTS: 8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population. MAIN OUTCOME MEASURES: Outcomes were incidence of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test result for SARS-CoV-2, and between 2017 and 2019 for background rates in the general population cohort. Indirectly standardised incidence ratios were estimated. Adjusted incidence rate ratios were estimated from the self-controlled case series. RESULTS: The study included 4 376 535 people who received ChAdOx1 nCoV-19, 3 588 318 who received BNT162b2, 244 913 who received mRNA-1273, and 120 731 who received Ad26.CoV.2; 735 870 people with SARS-CoV-2 infection; and 14 330 080 people from the general population. Overall, post-vaccine rates were consistent with expected (background) rates for Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome. Self-controlled case series was conducted only for Bell's palsy, given limited statistical power, but with no safety signal seen for those vaccinated. Rates were, however, higher than expected after SARS-CoV-2 infection. For example, in the data from the UK, the standardised incidence ratio for Bell's palsy was 1.33 (1.02 to 1.74), for encephalomyelitis was 6.89 (3.82 to 12.44), and for Guillain-Barré syndrome was 3.53 (1.83 to 6.77). Transverse myelitis was rare (<5 events in all vaccinated cohorts) and could not be analysed. CONCLUSIONS: No safety signal was observed between covid-19 vaccines and the immune mediated neurological events of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. An increased risk of Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome was, however, observed for people with SARS-CoV-2 infection.

Population-Based Incidence of Guillain-Barré Syndrome During Mass Immunization With Viral Vaccines: A Pooled Analysis.

Misunderstanding temporal coincidence of adverse events during mass vaccination and invalid assessment of possible safety concerns have negative effects on immunization programs, leading to low immunization coverage. We conducted this systematic review and meta-analysis to identify the incidence rates of GBS that are temporally associated with viral vaccine administration but might not be attributable to the vaccines. By literature search in Embase and PubMed, we included 48 publications and 2,110,441,600 participants. The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination, equally 2.47 per 100,000 person-year (95%CI: 2.14 to 2.81). Subgroup analyses illustrated that the pooled rates were 2.77 per million persons (95%CI: 2.47 to 3.07) for individuals who received the influenza vaccine and 2.44 per million persons (95%CI: 0.97 to 3.91) for human papillomavirus (HPV) vaccines, respectively. Our findings evidence the GBS-associated safety of virus vaccines. We present a reference for the evaluation of post-vaccination GBS rates in mass immunization campaigns, including the SARS-CoV-2 vaccine.