gms | German Medical Science

Background: The COVID-19 pandemic declared by the World Health Organization (WHO) in March 2020 continues, not least due to the now dominant, highly infectious delta variant.

A ray of hope in the fight against the pandemic are the m-RNA and vector-based COVID-19 vaccines, which have also been successively approved in the EU since the end of 2020, and which are highly effective in protecting against severe forms of SARS-CoV-2 infection.

A willingness to vaccinate in the population depends essentially but also on the tolerability of the vaccines.

Therefore, the reactogenicity of various COVID-19 vaccines will be evaluated by the collective of clinic employees actively in working life.

Materials and Methods: In the period from January to June 2021, a total of 1338 employees at the Helios Klinikum Hildesheim were vaccinated in a total of four cohorts in accordance with the applicable prioritization groups. Of these, 1206 subjects were included in the study, which corresponds to a study inclusion rate of 90%.

Over time, the selection of vaccines followed the applicable recommendations of the Ständige Impfkommission (STIKO).

This resulted in four different vaccine groups with a corresponding number of subjects: mRNA vaccine BNT162b2 (BioNTech/Pfizer) with a vaccination interval of 3 weeks (homologous BNT-3, n=248) and 6 weeks (homologous BNT-6, n=264) as well as two groups with ChAdOx1 prime vaccination (AstraZeneca) and homologous ChAdOx1 boost vaccination after 12 weeks (homologous AZ-12, n=270) or as a heterologous vaccination regimen with a BNT boost after 12 weeks (heterologous AZ-BNT-12, n=343).

As an intervention, the vaccine-mediated reactogenicity was recorded as local and systemic adverse drug reaction (ADRs) within one week after the first and second vaccination using standardized questionnaires.

The statistical analysis of categorical data is performed using frequencies, percentages and corresponding tests (Chi² test or Fisher’s exact test).

Results: The reactogenicity of the different vaccine combinations differed significantly after both first and second vaccination (p<0.001).

AZ’s vector vaccine caused local and/or systemic ADRs in more than 90% of subjects after initial administration, while more than one in four subjects showed no ADR after initial BNT vaccination (p<0.001).

The combination of local and systemic ADRs was significantly higher in the groups with AZ-prime vaccination at 67% and 74% respectively than after BNT initial vaccination (34% and 39% respectively). Chills and fever occurred more frequently in every second vaccinated person after AZ initial vaccination, and thus clinically relevant more frequently than under a BNT initial vaccination (50.8% vs. 3.8%, p<0.001).

The reactogenicity in comparison of the same vaccines naturally did not reveal any significant differences.

AZ was significantly less reactive after boost vaccination than after first dose.

The vaccine responses also differed to all BNT-vaccination groups analyzed (p<0.001). Thus, significantly fewer combined local and systemic ADRs occurred, whereas 44% of the subjects had no reactions after homologous AZ-vaccination.

A BNT-boost after three weeks was significantly more reactogenic (p=0.007) compared to six weeks. The combined occurrence of local and systemic ADRs differed significantly here (BNT-3: 70.8%; BNT-6: 59.3%), whereas the absence of any symptoms was more common during the longer vaccination interval (BNT-3: 6.5%; BNT-6: 17.0%).

The tolerability of a heterologous vaccination with a BNT-boost at 12 weeks was about as well tolerated as a homologous BNT-vaccination with a six-week interval (p=0.461) and less reactogenic than in the BNT-3-vaccination group (p=0.031).

The severity of vaccine-related ADRs was estimated by the presence of a resulting inability to work.

The frequency of incapacity for work was higher after initial vaccination than after boost vaccination (8.3% vs. 3.8%). The majority affected subjects after AZ initial vaccination (95.1% vs. 4.9% after BNT initial vaccination).

The distribution of incapacity for work after second vaccination correlates with the listed reactogenicity data above (BNT-3: 41.2%, BNT-6: 23.5%, AZ homologous 8.8%, AZ-BNT heterologous 26.5%).

Serious vaccination reactions with the need for medical care in a hospital did not occur.

The tolerability data of all vaccine combinations were additionally subjected to a gender stratified analysis.

Only in the BNT-3 cohort there was a statistically significant difference with increased reactogenicity in women after initial (p=0.016) and second vaccination (p=0.001) after three weeks. However, in a comparative analysis of vaccine reactions with other vaccine groups, this difference does not appear to be clinically relevant.

Conclusion: The four vaccine combinations analyzed differed clinically relevant and statistically significant regarding adverse reactions.

AstraZeneca’s vector vaccine was extremely reactive, especially after the initial vaccination, which was also reflected in the number of incapacities for work.

BNT as an m-RNA vaccine was more reactogenic after boost vaccination than after first administration, with tolerability significantly correlated with the timing of vaccination interval.

The tolerability of the heterologous vaccine combination with AZ initial vaccination and a BNT boost after 12 weeks showed good tolerability, which also seems promising in view of the upcoming booster vaccinations in the population with previously vector-based vaccination regimens in the future.

Clinically relevant gender differences in vaccine tolerances could not be recorded.