Previous COVID-19 infection but not Long-COVID is associated with increased adverse events following BNT162b2/Pfizer vaccination
Authors: Raw Rachael K. , Kelly Clive , Rees Jon , Wroe Caroline , Chadwick David R. 
Published: April 2021

AbstractImportanceUnderstanding Adverse Events (AEs) associated with SARS-CoV-2 vaccination has public health implications, especially with regards to vaccine hesitancy.ObjectiveTo establish whether individuals with prior history of COVID-19 were more likely to experience AEs after BNT162b2/Pfizer vaccination, than those without previous COVID-19, and whether COVID-19-vaccination interval influenced AE severity.DesignAn observational study explored AEs after vaccination. Participants were invited to complete an electronic survey, capturing self-reported COVID-19 symptoms, PCR/antibody results, and AEs following first dose of BNT162b2/Pfizer vaccine. In a subset where PCR/antibody results could be verified, a sensitivity analysis was conducted.SettingThree North-East England hospital Trusts in the United Kingdom.ParticipantsHealthcare workers formed an opportunistic sample – 265 of 974 reported prior positive SARS-CoV-2 PCR and/or antibody.ExposureAll participants had received their first dose of BNT162b2/Pfizer vaccine.Main Outcomes and MeasuresNature, severity, duration, and onset of self-reported AEs (reported via a modified version of the FDA Toxicity Grading Scale for vaccine-associated AEs), was compared between those with and without a prior history of COVID-19, using 2-way ANCOVA and logistic regression. Effects of age, gender, illness-vaccine interval, and ongoing symptoms (‘Long-COVID’) on AEs, were also explored.ResultsOf 974 respondents (81% female, mean age 48), 265 (27%) reported previous COVID-19 infection. Within this group (symptoms median 8.9 months pre-vaccination), 30 (11%) complained of Long-COVID. The proportion reporting one moderate/severe symptom was higher in the previous COVID-19 group (56% v 47%, OR=1.5 [95%CI, 1.1–2.0], p=.009), with fever, fatigue, myalgia-arthralgia and lymphadenopathy significantly more common. There was no significant relationship between illness-vaccine interval and symptom composite score (rs=0.09, p=.44). Long-COVID was not associated with worse AEs in comparison to the group without previous COVID-19. In the smaller sensitivity analysis cohort (412 people) similar findings were obtained although only myalgia and arthralgia remained significant.Conclusions and RelevancePrior COVID-19 infection but not ongoing Long-COVID symptoms were associated with an increase in the risk of self-reported adverse events following BNT162b2/Pfizer vaccination. COVID-19 illness-vaccination interval did not significantly influence AEs. This data can support education around vaccine-associated AEs and, through improved understanding, help to combat vaccine hesitancy.Key PointsQuestionDoes previous COVID-19 infection or ‘Long-COVID’ increase the frequency of Adverse Events (AEs) following first dose of BNT162b2/Pfizer vaccination?FindingsIn a survey-based observational study, healthcare workers in the United Kingdom reported AEs experienced after their first dose of BNT162b2/Pfizer vaccine. Prior COVID-19 infection, but not Long-COVID, were associated with increased risk of self-reported AEs including lymphadenopathy post-vaccination. Duration since COVID-19 infection did not affect severity of AEs.MeaningOur study can inform education and understanding of AEs associated with COVID-19 vaccination and help to combat vaccine hesitancy.