Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature.

Background: Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature. Methods: Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of 'any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination. Results: The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females. Discussion: The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature

Background Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature. Methods Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of ‘any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination. Results The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females. Discussion The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.

A case series of bacillus Calmette-Guérin scar reactivation after administration of both mRNA and viral vector COVID-19 vaccines.

AIM: Reactivation of the scar resulting from intradermal injection of bacillus Calmette-Guérin (BCG) is a common specific reaction in Kawasaki's disease. It has also sporadically been associated with viral infections, multisystem inflammatory syndrome in children, influenza vaccination and mRNA COVID-19 vaccination. In this case series, characteristics of BCG scar reactivation after different COVID-19 vaccinations are presented and possible mechanisms are discussed. METHODS: Data were collected from the spontaneous reporting system of the Netherlands Pharmacovigilance Centre Lareb. Descriptives were made for the case reports in which a BCG scar reactivation was detected. RESULTS: Since the start of the COVID-19 vaccination campaign in January 2021, the Netherlands Pharmacovigilance Centre Lareb has received 22 case reports of BCG reactivation after vaccination with a COVID-19 vaccine. In 20 case reports, it concerned mRNA COVID-19 vaccines Moderna (14) and Pfizer (6). In two case reports, the viral vector COVID-19 vaccine AstraZeneca was administered. Erythema and pain were the most frequently reported symptoms and the size of the inflammation was between 1.5 and 5 cm. BCG scar reactivation occurred with a median time to onset of 2 days after the second or booster COVID-19 vaccination, whereas the median time to onset was 7 days after the first COVID-19 vaccination. None of the BCG scar reactivations were treated. CONCLUSIONS: The exact mechanism of the occurrence of BCG scar reactivation remains unknown, but involvement of heat shock protein 65 is suggested. BCG scar reactivation is a nonserious, self-limiting reaction that can occur after vaccination with both mRNA and viral vector COVID-19 vaccines.

Description of Frequencies of Reported Adverse Events Following Immunization Among Four Different COVID-19 Vaccine Brands.

INTRODUCTION: The rapid rollout of coronavirus disease 2019 (COVID-19) vaccines for a large proportion of the population necessitates a strong emphasis on safety. Complementary to the existing spontaneous reporting system, The Netherlands Pharmacovigilance Centre Lareb conducted patient-reported cohort event monitoring (CEM). OBJECTIVE: The primary aim was to investigate differences in the frequencies of any and commonly reported, 'well-known', systemic adverse events following immunization (AEFIs) with four COVID-19 vaccines (Pfizer's Comirnaty®, Moderna's Spikevax®, AstraZeneca's Vaxzevria® and the Janssen vaccine). As a secondary aim, we analyzed the frequencies of well-known systemic adverse events after the first and, if applicable, second COVID-19 vaccinations, taking into account age, sex and prior COVID-19 infection. METHODS: Patient-reported outcomes (PROs) in the Netherlands starting in February 2021 were analyzed using a prospective cohort design. RESULTS: Data of 27,554 participants who received one vaccination and 20,682 participants who received complete immunization were analyzed. The percentage of patients reporting any AEFI was high and ranged from approximately 53% for the Pfizer vaccine to approximately 94% for the Moderna vaccine. The frequency of serious AEFIs was low, with the highest frequency found for the AstraZeneca vaccine (0.228%). AEFIs were most often experienced by participants receiving the first dose of the AstraZeneca and Janssen vaccines and the second dose of the Moderna vaccine; the Pfizer vaccine was associated with the lowest rate of AEFIs. Participants with a COVID-19 history before vaccination experienced commonly reported systemic AEFIs more frequently after the first vaccination than after the second vaccination. Women and young people experienced more AEFIs than men and older people, respectively. CONCLUSIONS: The analysis of a large cohort provides important information about the rates of AEFIs across age groups, among brands of vaccines and between those with and without prior COVID-19 infection. Participants reported a high number of AEFIs in general, but the frequency of serious AEFIs was low.

COVID-19 vaccine reactogenicity - A cohort event monitoring study in the Netherlands using patient reported outcomes.

OBJECTIVES: To explore factors that are associated with reactogenicity in general and systemic after the first dose of COVID-19 vaccine in the Netherlands. DESIGN: A web-based prospective cohort design using patient reported outcomes (PROs). SETTING: Any person who has been vaccinated with any brand of COVID-19 vaccine in the Dutch COVID immunization programme. PARTICIPANTS: 22,184 participants. Of these, 13,959 (62.9%) experienced reactogenicity in general and 11,979 (54.0%) systemic reactogenicity within 7 days after vaccination. MAIN OUTCOME MEASURES: Factors that are associated with the occurrence of reactogenicity after COVID-19 vaccination. RESULTS: Compared to the Comirnaty® vaccine, the highest odds ratio (OR) for developing reactogenicity was for the Vaxzevria® vaccine (OR 5.18) followed by Spikevax® (OR 2.16), and Janssen (OR 1.65). Participants with a history of COVID-19 disease had a 3.10 increased odds for reactogenicity. Women had a 2.08 increased odds compared to men. Older participants experienced less reactogenicity. Compared to the age group < 50, the ORs for the age groups 50-60, 61-79, and ≥80 were 0.36, 0.15, and 0.10 respectively. The use of an antipyretic drug, or a drug for nervous system disorders gave an increased odds of 1.34 and 1.16 respectively. A body mass index of 25.0-29.9 and over 30 was negatively associated with reactogenicity (OR 0.87 and OR 0.72 respectively). Comorbidities that were associated with reactogenicity were cardiac disorders (OR 1.26), respiratory disorders (OR 1.31), psychiatric disorders (1.37), reproductive disorders (OR 1.54), and eye disorders (OR 1.55). The factors associated with systemic reactogenicity were mostly comparable, but there were differences for comorbidities, drug use, and the strength of the regression coefficient. CONCLUSIONS: This extensive study with over 22,000 vaccine recipients in the Netherlands demonstrated that, taken into account all factors in the model, the Comirnaty® vaccine gave the least and the Vaxzevria® vaccine the most reactogenicity in general and systemic after the first dose. Also a person with a history of COVID-19 disease, female sex and younger age had an increased odds for experiencing reactogenicity after vaccination.