key: cord-0017848-i2yapyrm authors: Raw, Rachael Kathleen; Kelly, Clive; Rees, John; Wroe, Caroline; Chadwick, David title: Previous COVID-19 infection, but not Long-COVID, is associated with increased adverse events following BNT162b2/Pfizer vaccination. date: 2021-05-29 journal: J Infect DOI: 10.1016/j.jinf.2021.05.035 sha: 4019d754c029dc9ba36912e70750c0661f95f672 doc_id: 17848 cord_uid: i2yapyrm nan We read with interest the study recently published by Tré-Hardy et al. who reported that Adverse Events (AEs) after the first dose of mRNA-1273/Moderna vaccine were greater in those previously infected with COVID-19 1 . Their findings are consistent with other studies that suggest mRNA vaccines may cause more AEs in those with a history SARS-CoV-2 infection [2] [3] [4] . These results warrant further investigation into the effects of prior COVID-19 history on vaccine reactions, particularly whether time between previous infection and vaccination administration, or the presence of 'Long-COVID' [5] , can predict AEs. This information is important, as it could identify individuals more likely to experience side effects to COVID-19 vaccines. Furthermore, there are implications regarding vaccine hesitancy, which is partially driven by fear of AEs [6] . As part of an observational study of COVID-19 outcomes in healthcare workers in North-East England, we evaluated AEs following first doses of BNT162b2/Pfizer vaccine, with reference to previous COVID-19 and Long-COVID. Healthcare workers completed an electronic survey, which captured self-reported COVID-19 symptoms, PCR/antibody results, and AEs following first doses. The FDA Toxicity Grading Scale [7] was modified, allowing participants to self-report AEs for severity (mild/moderate/severe/very severe), duration (≤24 hours/>24 hours) and onset (≤24 hours/>24 hours); lymphadenopathy was also included. A composite score for symptom nature and severity was calculated, to provide an overall estimate of AE-related morbidity. Individual and composite AE scores were compared between those with and without a prior history of COVID-19, as indicated by self-reported prior positive antibody and/or PCR result. Long-COVID was defined as symptoms persisting for >2 months prior to vaccination. Effects of age, gender and time between past infection to vaccination were also considered. Respondents who permitted laboratory results to be accessed (SARS-CoV-2 PCR/antibody), formed a subgroup for a 'sensitivity analysis'. Statistical analysis was conducted using JASPv0.14.1.0. Composite scores were compared using 2-way ANCOVA. Multivariable logistic regressions were used, to identify the relationship between COVID-19 status and moderate/severe symptoms in each category, and the Bonferroni correction applied to the resulting significance/confidence intervals. This study of healthcare workers demonstrated that prior COVID-19, but not Long-COVID, was associated with increased risk of AEs following BNT162b2/Pfizer vaccination, although there was no relationship with duration since COVID-19 illness. Women and younger individuals were also more likely to report AEs. Our study adds to other reports supporting the wider understanding of AEs following COVID-19 vaccination [1] [2] [3] [4] . Importantly, given hesitancy surrounding recently developed COVID-19 vaccines [6] , our findings may help inform those with previous COVID-19 of increased susceptibility to certain AEs. Our study also adds weight to the question of whether a second dose of mRNA vaccine is necessary in those with previous COVID-19, assuming effective immunity is established after the first dose [1, 2, 8, 9] . This is relevant, given that Tre-Hardy's and other studies have reported worse AEs following second doses of vaccine [1, 3] . Our study has several limitations. Firstly, some non-responder bias [10] is likely, with 27% of participants reporting previous COVID-19. Secondly, AE information was gathered via selfreported questionnaires, hence subjective. Thirdly, PCR/antibody results were self-reported. We addressed this via a sensitivity analysis on a subset with laboratory data available, which mostly confirmed the findings. Finally, numbers of participants with Long-COVID were relatively small for comparison. safety and antibody response, after one and two doses of mRNA-1273 in seronegative and seropositive 7 Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19 Vaccine hesitancy' among university students in Italy during the COVID-19 pandemic Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study Assessing Response Rates and Nonresponse Bias in Web and Paper Surveys We would like to thank the CHOIS research team, John Rouse and the North East and NorthCumbria NIHR for assistance with the survey. The CHOIS study was supported by the North Healthcare Ltd, who provided assaysbut had no input into the study design. DRC/CK/RKR conceived the study and DRC is chief investigator of CHOIS. RKR acted as site principal investigator. DRC/RKR/CW contributed to the study protocol, design, and data collection. JR/RKR/DRC did the statistical analysis. RKR/JR/DRC prepared the manuscript.All authors critically reviewed and approved the final version. No conflicts of interest.