Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study

Abstract

Background In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines. Methods A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors. Results In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations. Conclusion The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety. Trial registration DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.

Reactogenicity Differences between COVID-19 Vaccines: A Pro-spective Observational Study in the United States and Canada

“…While there are limitations to direct comparisons between different studies, it is notable how closely these findings from the 2019nCoV-406 study mirror observations from the Oxford COV-BOOST trial and a National Institute for Allergy and Infectious Diseases and National Institutes of Health-funded booster study [26,27]. Results from this analysis of 2019nCoV-406 expand on previous reports [16,28,30] by focusing on the effects of vaccine doses administered after completion of primary COVID-19 vaccination series. Additional COVID-19 vaccine dosing, whether as the second dose of the primary series or as subsequent doses, can result in greater reactogenicity compared with the first injection [6,9,10], especially when receiving a heterologous booster [19,25,31].…”

“…Multiple studies have found greater reactogenicity of mRNA vaccines relative to other COVID-19 vaccine platforms, including adjuvanted protein-based vaccines such as NVX-CoV2373 [12,16,[25][26][27][28][29][30]. While there are limitations to direct comparisons between different studies, it is notable how closely these findings from the 2019nCoV-406 study mirror observations from the Oxford COV-BOOST trial and a National Institute for Allergy and Infectious Diseases and National Institutes of Health-funded booster study [26,27].…”

“…Local and systemic reactions are also commonly reported for immunizations targeting infectious diseases other than COVID-19 (e.g., influenza or shingles) [13,14]. Of note, studies comparing reactogenicity have generally found a higher incidence of local and systemic events following receipt of mRNA COVID-19 vaccines compared with influenza and other non-COVID-19 vaccines, as well as a higher frequency of reactogenicity-associated medication use, sick leave, and doctor's visits [15,16]. COVID-19 vaccine-related reactogenicity events can affect work and other daily activities, leading to absenteeism from work [17,18] and presenteeism [17,19], as well as vaccine hesitancy [20][21][22][23][24].…”

Burden and Impact of Reactogenicity among Adults Receiving COVID-19 Vaccines in the United States and Canada: Results from a Prospective Observational Study

“…In addition, the reactogenicity of the NVX-CoV2373 booster observed in 2019nCoV-406 is consistent with the percentage reported in the US FDA Healthcare Provider Fact Sheet [ 36 ]. A recent meta-analysis of reactogenicity among COVID-19 vaccine types found mRNA vaccines to be more reactogenic and to lead to greater impairment than inactivated vaccines [ 37 , 38 ]. The observed pattern of greater reactogenicity following mRNA compared to NVX-CoV2373 from 2019nCoV-406 is in agreement with previous investigations of COVID-19 vaccine safety, including the Oxford COV-BOOST trial and a National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) funded booster study [ 39 , 40 , 41 , 42 ].…”