Interpretation of vaccine associated neurological adverse events: a methodological and historical review

Marija Cauchi,Neil Robertson,Harriet Ball,Yoav Ben-Shlomo

doi:10.1007/s00415-021-10747-8

Marija Cauchi, Neil Robertson + Show 2 more

Open Access

https://doi.org/10.1007/s00415-021-10747-8

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Abstract

As a result of significant recent scientific investment, the range of vaccines available for COVID-19 prevention continues to expand and uptake is increasing globally. Although initial trial safety data have been generally reassuring, a number of adverse events, including vaccine induced thrombosis and thrombocytopenia (VITT), have come to light which have the potential to undermine the success of the vaccination program. However, it can be difficult to interpret available data and put these into context and to communicate this effectively. In this review, we discuss contemporary methodologies employed to investigate possible associations between vaccination and adverse neurological outcomes and why determining causality can be challenging. We demonstrate these issues by discussing relevant historical exemplars and explore the relevance for the current pandemic and vaccination program. We also discuss challenges in understanding and communicating such risks to clinicians and the general population within the context of the ‘infodemic’ facilitated by the Internet and other media.

Highlights

As a result of a rapid and focussed international scientific response to the COVID-19 pandemic, an impressive array of vaccines against SARS-CoV-2 is available and the largest vaccination program in history is well underway
International retrospective cohort studies performed on newly diagnosed narcolepsy patients [75,76,77,78,79,80,81] and a recent meta-analysis have estimated an increase in relative risk of 5–14-fold in vaccinated children and adolescents, and 3–8-fold in adults within the first year of vaccination with Pandremix [82]
Any new vaccine will have been carefully studied in large randomised trials before licencing

Summary

Introduction

As a result of a rapid and focussed international scientific response to the COVID-19 pandemic, an impressive array of vaccines against SARS-CoV-2 is available and the largest vaccination program in history is well underway. Monitoring of real-world vaccine experience via passive and active surveillance systems facilitates early detection, investigation, and analysis of adverse events following immunization [8] and are a key tool in developing an understanding of longer term and low frequency events as well as contextualising risks An example of this that could not have been detected in the phase 3 trials were thrombotic cases associated with thrombocytopenia and antibodies to PF4 reported following the AstraZeneca (AZ) and Jannsen vaccinations [9,10,11]. Systematic incidence data are lacking; at best a case (listed as FND or conversion disorder) will be mentioned in passing in studies set up to look for other conditions [25,26,27] Such events are more likely to occur in settings where many (especially young) patients are vaccinated at once [28]. There appears to be a consensus for a small association between influenza vaccines and GBS, but the risk is consistently very low (~ 1–3 additional GBS cases per million vaccinations) [46] and needs to be carefully weighed against evidence supporting benefits of vaccination in preventing influenza-related complications, including an increased risk of GBS [43, 47]

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