key: cord-0702224-k91ln6vh authors: Cuschieri, Sarah; Borg, Michael; Agius, Steve; Souness, Jorgen; Brincat, Andre; Grech, Victor title: Adverse reactions to Pfizer‐BioNTech vaccination of healthcare workers at Malta's state hospital date: 2021-07-19 journal: Int J Clin Pract DOI: 10.1111/ijcp.14605 sha: e793d973c39bc8a176c4c67171ae98a16334c5e4 doc_id: 702224 cord_uid: k91ln6vh BACKGROUND: The long‐term control of COVID‐19 depends on an effective global vaccination strategy. Protecting healthcare workers (HCWs) from serious infection is critical. Malta, a European country, initiated the vaccination roll‐out using Pfizer‐BioNTech COVID‐19 vaccine targeting HCWs. This study determined vaccination adverse effects (AEs) in this cohort. METHOD: An online survey was disseminated to all HCWs via work email (29/3/21 to 9/4/21) to gather AEs regarding pain, redness and swelling at injection site, fever, chills, fatigue, muscle/joint pains, headache, vomiting and diarrhoea severity following each dose (Likert scale). Descriptive, comparative and multiple binary regression analyses were performed. RESULTS: A response of 30.30% (n = 1480) was achieved with the commonest AEs being pain at injection site (88.92% CI 95%: 87.21‐90.42), mostly mild (51%) and moderate (43%). Fatigue was reported by 72.97% (CI 95%: 70.65‐75.17), 42% were mild and 41% were moderate. Females reported significantly (P ≤ .05, respectively) more pain (OR: 1.90), redness (OR: 2.49), swelling at injection site (OR: 1.33), fever (OR: 1.74), chills (OR: 2.32), fatigue (OR: 2.43), muscle (OR: 1.54) and joint pains (OR: 2.01), headache (OR: 2.07) and vomiting (OR: 3.43) when adjusted for age and HCW role. Localised AEs were reported following both vaccine doses unlike systemic AEs that were mostly reported after second doses. CONCLUSION: Vaccination benefits outweigh the minor AEs experienced, with females exhibiting a higher susceptibility. The general low vaccination AEs observed within the HCW cohort is encouraging and should help in allaying vaccine hesitancy among the population. 2020. 6, 7 Vaccination was undertaken using the Pfizer-BioNTech COVID-19 vaccine through the manufacturer-recommended twodose protocol, 3 weeks apart. This study was carried out in order to determine the degree and nature of adverse effects to this cohort of HCWs. Vaccinees were emailed a personal invitation to complete an anonymised questionnaire in a bespoke Google form after the vaccination drive was concluded. Data collection was performed from 29/03/21 to 09/04/21. The Google form did not record any identifiable variables or the participant's computer IP address, to ensure responders' privacy. Respondents were asked questions on basic demographics (sex and age), role (nurse, doctor, etc) and specific questions pertaining to known adverse effects. These included local reactions at the vaccination site (pain, redness and swelling) and more generalised systematic symptoms (fever, chills, fatigue, muscle/joint pains, headaches, vomiting and diarrhoea). For each of these, respondents were asked to grade severity on a Likert scale of five. They were also queried if the adverse effect was experienced with the first, the second or both doses, and at what day after the vaccine did this peak. Respondents were also asked whether they needed to take days off. The University of Malta Research and Ethical Committee granted clearance to conduct this study (ID: 7304_03122020). Data protection clearance was obtained from the Mater Dei Hospital data protection office. Statistical analyses were performed using IBM SPSS (IBM Corp. Release 2012 Version 21). Descriptive analyses are presented through frequencies. Comparative analyses were conducted through Chi Square test. Multivariable binary logistic regressions were performed with the different adverse effects as the dependent variables and sex, age and role as the independent variables. A P-value of ≤.05 was considered as significant. The questionnaire was sent to 4885 vaccinees. A total of 1480 responded (30.30% response rate), with a female predominance (66.69% CI 95%: 64.25-69.04). The characteristics of the participants are shown in Table 1 . The commonest reported adverse effects were "pain at injection site" followed by "fatigue." Females reported a higher incidence of adverse effects when compared with males ( Table 2 ). Those experiencing adverse effects mostly recalled the severity of these effects to be "mild" to "moderate." Only a small proportion of participants recalled having "severe" or "very severe" adverse effects. However, "severe fatigue" was reported by a higher proportion of males and females when compared with the other effects. The majority of the adverse effects was reported by the younger cohorts (<45 years of age) irrelevant of their sex ( Table 3) . As a general trend, localised adverse effects were mostly reported following both doses of the vaccine, while systemic adverse effects mostly were experienced after the second dose ( • This is an independent study to evaluate the adverse effects reported among the healthcare workers in Malta. • This is a population-based study that not only explored the adverse effects of Pfizer-BioTech vaccine but also evaluated whether there are contributing factors that increase susceptibility for adverse effects. were noted. 9 Our results also coincide with other independent studies conducted among HCWs. 10, 11 Indeed, similar to this study, the commonest reported adverse effect was mild-to-moderate pain at the injection site and mostly among the younger cohorts. 9 According to the manufacturer and other independent studies, fatigue and headaches were the second and third most common adverse effects, mostly following the second dose and again among the young cohorts. [9] [10] [11] In this study, we observed a slight variation to these reports. Whilst fatigue was the second commonest adverse effect among our cohort, muscle pains and chills were reported as more frequent adverse effects than headaches. However, on comparing the frequency of headaches, similar proportions were noted (this study: 44.26%; manufacturer: 40.06%; Riad et al: 45.6%; Kadali et al: 45.48%). [9] [10] [11] Another variation noted was the frequency of "severe fatigue" as an adverse effect. Our study cohort reported a much higher frequency (12.57%) of "severe fatigue" than that reported by the manufacturer (3.8%). 9 A unique finding in this study was the link between females and their susceptibility to all adverse effects (except diarrhea, potentially because of small numbers). This was not reported by the manufacturer, although a study conducted in Saudi Arabia established a comparative difference in frequency of adverse effects between females and males. 12 Sex differences in disease severity and susceptibility have been previously reported for autoimmune diseases, cancers and infectious diseases among other. 13, 14 Indeed, females have higher morbidity and mortality susceptibility for influenza and HIV. 15 This has been reported to be a consequence of differences in endocrine and sex hormones that contribute to different immune responses between males and females, with an effect on disease susceptibility and vaccination outcome. 16 It has also been observed that females tend to mount greater vaccine immune responses than males. 16, 17 Sex differences have also been noted to influence pharmacokinetics and pharmacodynamics, with females more susceptible to adverse effects. These effects have been linked to females' higher body fat content when compared with males, affecting the volume of distribution and clearance of drugs. 18, 19 This may be another plausible explanation to this study's results. Another potential reason is different behavioural attitudes between females and males. In fact, it has been reported that females tend to report adverse effects more than males. 20 This was an observational survey that was distributed through elec- Short-term adverse reactions of the Pfizer-BioNTech COVID-19 vaccine have now been established, with a proclivity for the female population and the younger ages. However, on weighing the benefits of vaccination against the risks of acquiring severe Covid-19 infection or development of what appears to be mostly mild to moderate short adverse effects following vaccination, the benefits greatly outweigh these risks. The general low vaccination adverse effects observed within the HCWs cohort is encouraging and should help in allaying vaccine hesitancy among the population. It is recommended that a follow-up study at 3-, 6-and 12-months intervals is carried out to note down longer term COVID-19 and vaccine adverse effects. The authors declare that there is no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Cuschieri https://orcid.org/0000-0003-2012-9234 Planning for a COVID-19 vaccination program High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2 Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review Vaccine hesitancy: the next challenge in the fight against COVID-19 Lessons learned from frontline skilled nursing facility staff regarding COVID-19 vaccine hesitancy Vaccines. Ministry of Health Malta Mater Dei nurse receives first COVID-19 vaccine in Malta. Times of Malta The Advisory Committee on Immunization Practices' interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine -United States Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Prevalence of COVID-19 vaccine side effects among healthcare workers in the Czech Republic Side effects of BNT162b2 mRNA COVID-19 vaccine: a randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers Minor to moderate side effects of Pfizer-BioNTech COVID-19 vaccine among Saudi residents: a retrospective cross-sectional study Gender differences in cancer susceptibility: an inadequately addressed issue The prevalence of autoimmune disorders in women: a narrative review. Cureus. 12. Epub ahead of print 2020 Mechanisms of sex disparities in influenza pathogenesis Sex differences in immune responses Sex-based differences in immune function and responses to vaccination Gender differences in pharmacological response Sex differences in pharmacokinetics predict adverse drug reactions in women Sex and gender differences in the outcomes of vaccination over the life course Adverse reactions to Pfizer-BioNTech vaccination of healthcare workers at Malta's state hospital