Adverse Events Associated with Influenza Vaccine, by Vaccine Type

Simon de Lusignan

Adverse events from the influenza vaccine, no matter the type, typically occur within the first 7 days post-vaccination, according to a paper published in The Lancet Regional Health – Europe.

Investigators from the UK conducted a retrospective cohort study of electronic health records in order to compare the safety profiles between the cell-based quadrivalent influenza vaccine (QIVc) and the alternative egg-based quadrivalent (QIVe) and adjuvanted trivalent influenza (aTIV) vaccines.

They examined the relative incidence of adverse events of interest over different risk periods, and then compared those within 7 days over vaccination overall. They also compared the data between different age groups and vaccination types.

All patients who had received a seasonal flu vaccine between September 1, 2019 and April 30, 2020 were included in the analysis. However, the investigators excluded patients aged over 100 years and those who received monovalent pandemic flu vaccines.

The study authors collected data regarding the patients’ age, sex, self-reported ethnicity, socioeconomic status, vaccination date, vaccine type, vaccine manufacturer, and date and type of adverse events of interest. They also noted the previous season’s adverse events of interest because in prior research, they said, they found year-on-year changes of adverse events of interest.

More than 1.1 million patients met the inclusion criteria, the study authors said. The mean age was 56 years, there was a slight female majority (54%) and most patients (72%) were white.

The researchers observed adverse events of interest in every European Medical Agency category, most commonly arthropathy, cough, and rash. Those that were most frequently reported within the first 7 days of vaccination included wheezing, nasal congestion, and cough. More severe conditions such as Guillain-Barré syndrome (1 patient) and anaphylaxis (6 patients) were rare within the first 7 days after vaccination.

The 7 days post-vaccination showed a doubled risk of adverse events of interest, compared to days 7 to 13 post-vaccine and days 14-45 post-vaccine. Those other 2 periods had only a marginally increased relative incidence. The fourth pre-specified risk period, the 7 days leading up to vaccine, was associated with a 6 percent lower relative incidence of adverse events of interest. The study authors wrote that this reflects the “healthy vaccinnee” effect which other studies have discussed.

The study authors also found a seasonal pattern among adverse events of interest. They used the first 30 days as a reference and noted that the third, fifth, and sixth seasonal periods showed an increase in adverse events of interest, but the fourth, seventh, and eighth seasonal periods showed a decrease. These decreased periods roughly corresponded to when the United Kingdom went into a national lockdown caused by the coronavirus disease 2019 (COVID-19) pandemic.

When examining adverse events of interest among vaccination types, the study authors learned that QIVc and QIVe were associated with similar incidence of adverse events of interest. Live attenuated influenza vaccine (LAIV) and aTIV had a 43% and 26% lower relative incidence than cell-based quadrivalent influenza vaccine, respectively.

“Overall, the incidence of AEIs in the seven days post-vaccination did not appear to differ among patients who received QIVc or QIVe, but aTIV and LAIV were associated with lower risk incidences of adverse events of interest,” the study authors said, noting that this matched observations from the 2018-19 flu season.