Abstract

Keywords

۱٫ Preamble

۲٫ Rationale for selected decisions about the case definition of vaed/vaerd as an adverse event following immunization

۳٫ Case definition of vaccine associated enhanced disease (VAED)

Declaration of Competing Interest

Acknowledgements

Disclaimer

Appendix A. Supplementary material

References

Abstract

This is a Brighton Collaboration Case Definition of the term “Vaccine Associated Enhanced Disease” to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.

۱٫ Preamble

Vaccine-associated enhanced diseases (VAED) are modified presentations of clinical infections affecting individuals exposed to a wild-type pathogen after having received a prior vaccination for the same pathogen [1]. Vaccine-associated enhanced respiratory (VAERD) disease refers to disease with predominant involvement of the lower respiratory tract. Classic examples of VAED are atypical measles and enhanced respiratory syncytial virus (RSV) occurring after administration of inactivated vaccine for these pathogens. In this situation, severe disease has been documented resulting from infection in individuals primed with non-protective immune responses against the respective wild-type viruses [2], [3], [4], [5], [6]. Given that these enhanced responses are triggered by failed attempts to control the infecting virus, VAED typically presents with symptoms related to the target organ of the infection pathogen. In order to recognize vaccine associated disease enhancement, it is therefore necessary to have a clear understanding of the clinical presentation and usual course of the natural disease.

Disease enhancement independent of vaccine priming has also been described for pathogens causing sequential infections with different cross-reactive but not cross-protective serotypes, including dengue and pandemic influenza [7], [8], [9], [10], [11], [12].

In late 2019, a novel severe respiratory illness emerged in Wuhan, China [13]. The causative agent, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was promptly identified, and determined to be closely related to SARS and the Middle East Respiratory Syndrome (MERS) coronaviruses, which had caused geographically localized outbreaks in 2002–۲۰۰۴ and from 2012 onwards, respectively. SARS-CoV-2 progressed to a global pandemic with substantial consequences due to its high infectivity and transmissibility, and its ability to cause both a severe respiratory illness, and a systemic disease with fatal consequences for vulnerable populations. The natural history of coronavirus infectious disease caused by SARS-CoV-2 (COVID-19), is yet to be fully described. However, a case fatality rate that ranges from 0.5% to nearly 20% depending on age and other risk factors, and the understanding that SARS-CoV-2 is now a well-adapted human pathogen that will continue to cause disease in susceptible populations, makes the development of an effective vaccine a global priority.