Guillain-Barre Syndrome and Adjuvanted Pandemic Influenza A (H1N1) 2009 Vaccines: A Multinational Self-Controlled Case Series in Europe

Background: The risk of Guillain-Barre syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1) pdm09 vaccination. Methods: A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. Results: Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1) pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1) pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2-5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7-2.8), which is the main finding. Conclusion: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1) pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8). Based on the upper limits of the pooled estimate we can rule out with 95% certainty that the number of excess GBS cases after influenza A(H1N1) pdm09 vaccination would be more than 3 per million vaccinated

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

The coronavirus disease 2019 (COVID-19) pandemic is concerning for patients with neuroimmunological diseases who are receiving immunotherapy. Uncertainty remains about whether immunotherapies increase the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or increase the risk of severe disease and death upon infection. National and international societies have developed guidelines and statements, but consensus does not exist in several areas. In this Review, we attempt to clarify where consensus exists and where uncertainty remains to inform management approaches based on the first principles of neuroimmunology. We identified key questions that have been addressed in the literature and collated the recommendations to generate a consensus calculation in a Delphi-like approach to summarize the information. We summarize the international recommendations, discuss them in light of the first available data from patients with COVID-19 receiving immunotherapy and provide an overview of management approaches in the COVID-19 era. We stress the principles of medicine in general and neuroimmunology in particular because, although the risk of viral infection has become more relevant, most of the considerations apply to the general management of neurological immunotherapy. We also give special consideration to immunosuppressive treatment and cell-depleting therapies that might increase susceptibility to SARS-CoV-2 infection but reduce the risk of severe COVID-19