Causality assessment of adverse events following immunization: the problem of multifactorial pathology

Abstract

The analysis of Adverse Events Following Immunization (AEFI) is important in a balanced epidemiological evaluation of vaccines and in the issues related to national vaccine injury compensation programs. If manufacturing defects or vaccine storage and delivering errors are excluded, the majority of adverse reactions to vaccines occur as excessive or biased inflammatory and immune responses. These unwanted phenomena, occasionally severe, are associated with many different endogenous and exogenous factors, which often interact in complex ways. The confirmation or denial of the causal link between an AEFI and vaccination is determined pursuant to WHO guidelines, which propose a four-step analysis and algorithmic diagramming. The evaluation process from the onset considers all possible "other causes" that can explain the AEFI and thus exclude the role of the vaccine. Subsequently, even if there was biological plausibility and temporal compatibility for a causal association between the vaccine and the AEFI, the guidelines ask to look for any possible evidence that the vaccine could not have caused that event. Such an algorithmic method presents some concerns that are discussed here, in the light of the multifactorial nature of the inflammatory and immune pathologies induced by vaccines, including emerging knowledge of genetic susceptibility to adverse effects. It is proposed that the causality assessment could exclude a consistent association of the adverse event with the vaccine only when the presumed "other cause" is independent of an interaction with the vaccine. Furthermore, the scientific literature should be viewed not as an exclusion criterion but as a comprehensive analysis of all the evidence for or against the role of the vaccine in causing an adverse reaction. These issues are discussed in relation to the laws that, in some countries, regulate the mandatory vaccinations and the compensation for those who have suffered serious adverse effects.

A Large Cluster of New Onset Autoimmune Myositis in the Yorkshire Region Following SARS-CoV-2 Vaccination

“…As suggested by World Health Organization (WHO) guidance [ 17 ], Adverse Events Following Immunization (AEFI) represent untoward medical events following vaccination. According to WHO, vaccines could represent the primary factor linked to AEFI or cofactors within complex events [ 18 ], although this approach has shortcomings, but robust alternatives are lacking [ 19 ]. After validating myositis diagnosis and excluding non-vaccination-related causes, biological plausibility and temporal compatibility between the immunization and the occurrence of the AEFIs were assessed as previously described [ 20 ].…”

Atypical Kawasaki Disease after COVID-19 Vaccination: A New Form of Adverse Event Following Immunization

“…Other studies found no evidence of an association between KD and PCV13, PCV 7, or 4CMenB vaccines [17]. However, the vaccine can act as a factor or cofactor with underlying predisposing conditions related to the biological or genetic makeup of the individual and the interaction of multifactorial environmental variables [18]. SARS-CoV-2 infection is known to exacerbate known rheumatologic disease, unmask previously undiagnosed rheumatic conditions, and precipitate de novo disease, which may persist after resolution of the infection.…”

First vaccination after birth: serious adverse events of Bacillus Calmette-Guérin (BCG) in real-world

“…The difficulty of identifying vaccine-related adverse reactions lies in judging the correlation between the vaccine and the events. 11 At the court’s request, all 14 adverse event reports were reviewed by a panel of five senior clinical experts to assess the causal relationship between adverse events and BCG vaccination. The committee determined that 7 cases had a possible cause-and-effect relationship with the vaccine, including 3 lymphadenitis, 1 disseminated BCGs, 1 myocarditis, and 1 epilepsy ( Table 1 ).…”