key: cord-0977816-86hssp2f
authors: Hillus, D.; Tober-Lau, P.; Hastor, H.; Helbig, E. T.; Lippert, L. J.; Thibeault, C.; Solarek, A.; Kalle, C. v.; Corman, V. M.; Kopankiewicz, P.; Suttorp, N.; Bias, H.; Seybold, J.; Kurth, F.; Sander, L. E.
title: Reactogenicity of homologous and heterologous prime-boost immunization with BNT162b2 and ChAdOx1-nCoV19: a prospective cohort study
date: 2021-05-22
journal: nan
DOI: 10.1101/2021.05.19.21257334
sha: 31992aadf8ff87490f700a8929de4a1d05c99a78
doc_id: 977816
cord_uid: 86hssp2f

Heterologous prime-boost vaccination is of increasing interest for COVID-19 vaccines. Evidence of rare thrombotic events associated with ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) has lead several European countries to recommend a heterologous booster with mRNA vaccines for certain age groups (e.g. persons <60years in Germany), who have already received one dose of ChAdOx, although data on reactogenicity and safety of this vaccination regimen are still missing. Here we report reactogenicity data of homologous BNT162b2 (Comirnaty, BNT) or heterologous ChAdOx/BNT prime-boost immunisations in a prospective observational cohort study of 326 healthcare workers. Reactogenicity of heterologous ChAdOx/BNT booster vaccination was largely comparable to homologous BNT/BNT vaccination and overall well-tolerated. No major differences were observed in the frequency or severity of local reactions after either of the vaccinations. In contrast, notable differences between the regimens were observed for systemic reactions, which were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT boosters (48%, 95CI: 36-59). This interim analysis supports the safety of currently recommended heterologous ChAdOx/BNT prime-boost immunisations with 12-week intervals.

Heterologous prime-boost vaccination is of increasing interest for COVID-19 vaccines. Evidence of rare thrombotic events associated with ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) has lead several European countries to recommend a heterologous booster with mRNA vaccines for certain age groups (e.g. persons <60years in Germany), who have already received one dose of ChAdOx, although data on reactogenicity and safety of this vaccination regimen are still missing. Here we report reactogenicity data of homologous BNT162b2 (Comirnaty, BNT) or heterologous ChAdOx/BNT prime-boost immunisations in a prospective observational cohort study of 326 healthcare workers. Reactogenicity of heterologous ChAdOx/BNT booster vaccination was largely comparable to homologous BNT/BNT vaccination and overall well-tolerated. No major differences were observed in the frequency or severity of local reactions after either of the vaccinations. In contrast, notable differences between the regimens were observed for systemic reactions, which were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT boosters (48%, 95CI: 36-59). This interim analysis supports the safety of currently recommended heterologous ChAdOx/BNT prime-boost immunisations with 12-week intervals.

Heterologous prime-boost vaccination is of increasing interest for COVID-19 vaccines 1 . Evidence of rare thrombotic events associated with ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) 2,3 , has lead several European countries to recommend a heterologous booster with mRNA vaccines for certain age groups (e.g. persons <60years in Germany), who have already received one dose of ChAdOx, despite a lack of data on reactogenicity and safety of this vaccination regimen 4 . A recent study showed increased reactogenicity of a heterologous boost with BNT162b2 (Comirnaty, BNT) 28 days after ChAdOx vaccination compared to homologous prime-boost 5 . Nearly 80% of participants in the ChAdOx/BNT group reported systemic reactions 5 . Here we report reactogenicity data of homologous BNT/BNT or heterologous ChAdOx/BNT prime-boost immunisations in a cohort of 326 healthcare workers recruited between 27 December 2020 to 30 March 2021 in Berlin, Germany. No major differences were observed in the frequency or severity of local reactions after either of the vaccinations (Fig. 1A, B) . In contrast, notable differences between the regimens were observed for systemic reactions, which were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT boosters (48%, 95CI: 36-59) (Fig. 1C) . Similarly, severe systemic symptoms, including fatigue, myalgia, headache, feeling feverish, chills, and fever >38°C, were more frequent following . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) ChAdOx prime immunisation compared to heterologous ChAdOx+BNT booster vaccination (Fig. 1C, D) . Antipyretic medication was reported most frequently after the first dose of ChAdOx (Fig. 1E) . Prophylactic intake of antipyretic medication at least 2 hours before vaccination was highest in the ChAdOx prime immunisation group (26.4%, 95CI: 20-34), and distinctly lower in all other groups (BNT: 2.8% (95CI: 1-7), ChAdOx/BNT: 5.6% (95CI: 2-15), BNT/BNT: 3.1% (95CI: 1-8) .

Reactogenicity of heterologous ChAdOx/BNT booster vaccination was largely comparable to homologous BNT/BNT vaccination and overall well-tolerated in our cohort of health care workers. In addition to differences in the study designs and in the demographics of the study populations (current study: median 34 years, 59.65% female vs. ComCov: median 57 years, 46% female), we propose that an increased vaccine interval (12 vs. 4 weeks) limits reactogenicity of heterologous ChAdOx/BNT vaccination. Thus, our study supports the current recommendations for 12-week vaccine intervals for heterologous ChAdOx/BNT prime-boost immunisations 4 . These results need to be confirmed in larger populations and evaluated together with immunogenicity data of heterologous prime-boost vaccination, about to be reported.

. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Could mixing COVID vaccines boost immune response?

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

BNT 178/179 (99.44%)

The authors thank Andreas Hetey, Maria Rönnefahrt, and the entire staff at the Charité Clinical Study Center (CSC), as well as the team at the Center for Occupational Medicine, and all study participants at Charité -Universitätsmedizin Berlin. This study was supported by the Forschungsnetzwerk der Universitätsmedizin zu Covid-19, COVIM -FKZ: 01KX2021.

Methods We performed a prospective, observational cohort study to assess safety and reactogenicity of COVID-19 vaccination in healthcare workers at Charité -Universitätsmedizin Berlin. The study was approved by the IRB (EA4/245/20). Participants were enrolled into the study prior to initial vaccination according to national vaccine guidelines, after giving written informed consent. All participants were asked to fill out electronic questionnaires on reactogenicity, adverse events, medication, and medical visits on days 1, 3, 5 and 7 post first and second vaccination. In addition, the use of antipyretic medication (NSAID, acetaminophen) before or after vaccination was recorded. We assessed solicited local and systemic reactions to the different vaccines based on the Food and Drug administration (FDA) toxicity scale 6 . Following the initial assessments on day 1, 3, 5 and 7, all participants were asked every 14 days to self-report any systemic symptoms and intake of pain medication. Intake of antipyretic or analgesic medication was not generally recommended for vaccinees, but also not discouraged. We report here on all symptoms and events recorded in the first seven days after prime and boost vaccination. Three participants chose a homologous ChAdOx+ChAdOx booster immunisation and were only included for reactogenicity analysis after first immunisation. Nineteen participants from the 1. BNT subgroup were lost to follow-up at the time of their second vaccination. Reactogenicity data after first vaccination with BNT or ChAdOx were available for 178 and 148 subjects, respectively, and for 159 individuals after BNT/BNT homologous boost, and for 71 after heterologous ChAdOx/BNT boost, respectively. Reactogenicity was graded according to modified Food and Drug administration (FDA) criteria 6 .

Available Reactogenicity Data (n) Median Age Female