gms | German Medical Science

Background and status of (inter)national research: An association between the administration of the COVID-19 vaccine ChAdOx1 (AstraZeneca) and the occasional occurrence of thromboembolic events has been detected as of March 2021. For individuals having received one dose of ChAdOx1, several countries recommended to complete the immunization series with an mRNA vaccine. However, data on safety and reactogenicity of these heterologous regimens were still scarce.

Research question and objective: As part of the CoVaKo safety study, we aimed to compare the reactogenicity and frequency of medical consultations (outpatient and inpatient) after the second vaccination in a heterologous regimen with ChAdOx1 and a mRNA vaccine with homologous regimens with only ChAdOx1 or mRNA vaccines (BNT162b2, BioNTech/Pfizer or mRNA-1273, Moderna), respectively.

Method or hypothesis: In an observational cohort study reactogenicity and safety were assessed 14 to 19 days (short-term) and 40 to 56 days (long-term) after the boost vaccination via web-based surveys. The short-term survey assessed solicited and unsolicited reactions along with possible consequences like medication intake, sick-leave, outpatient consultation or hospital admission. The long-term survey focussed on health problems leading to medical consultation or hospital admission after the vaccination, including those that were not suspected to be vaccine-related. Additionally, participants were asked about suspected association between their health problems and the vaccination and if they suspected long-term consequences.

Results: In total, 9146 participants completed at least one of the surveys (ChAdOx1/ChAdOx1: n = 552, ChAdOx1/mRNA: n = 2382, mRNA/mRNA: n = 6212). In the short-term survey, 86% with ChAdOx1/mRNA regimen reported at least one reaction, in the ChAdOx1/ChAdOx1 and mRNA/mRNA cohorts 58% and 76%, respectively (age and sex adjusted p < 0.0001). Participants reported, among local reactions, fatigue, headache and muscle or joint pain most often. In the long-term survey, comparable proportions of individuals reported medical consultations (ChAdOx1/ChAdOx1 vs. ChAdOx1/mRNA vs. mRNA/mRNA: 15% vs. 18% vs. 16%, age and sex adjusted p = 0.398). Out of those participants 4.3% to 5.6% suspected an association between their health problem and the vaccination. Female gender was associated with a higher reactogenicity and more medical consultations. Younger age was associated with a higher reactogenicity, whereas elderly people reported more medical consultations.

Discussion: Although the short-term reactogenicity with the heterologous regimen was higher than with the homologous regimens there was no significant difference in medical consultations after six weeks. In line with other studies, our results show that the heterologous regimen seems to be tolerable.

Practical implications: The reactogenicity with a heterologous regimen might be higher, but other factors such as a higher efficacy and limited resources during the pandemic may prevail in recommending specific regimens.

Appeal for practice (science and/or care) in one sentence: Further research is necessary to surveil the safety of the different vaccines and their combinations.

Funding: Einzelförderung (BMG, DRV, BMBF, DFG, etc)