Covid-19 Living Data

Trial EudraCT 2021-002693-10
Publication Mrak D, Nat Commun, 2022
Dates: 2021-07-22 to 2021-09-10
Funding: Public/non profit (The study was supported by the MedUni Vienna Biobank KIP. Provision of vaccines and laboratory testing was provided free of charge by the City of Vienna and the Medical University of Vienna via the Vienna General Hospital. Laboratory testing was supported by the Medical-Scientific fund of the Mayor of the federal capital Vienna to J.A.)
Conflict of interest: Yes

Methods
	RCT
	Location : Single center / Austria Follow-up duration (months): 0.9
	BNT162b2 or mRNA-1273 (n = 26) ChAdOx1 (n = 25)
Inclusion criteria	Adults (age ≥ 18 years) immunocompromised or under immunosuppressive treatment (either primary or secondary immunodeficiency or been treated with immunosuppressive therapy within the last 12 months. Immunosuppressive therapies include glucocorticoids, cytostatics, antibodies, drugs acting on immunophilins and other treatments like interferons and TNF binding proteins and exclude patients under B cell depleting therapy like Rituximab, Ocrelicumab, Ofatumumab, Epratuzumab or Obinutuzumab) without measurable SARS-CoV-2 spike protein-specific antibodies (<1500 U/ml) at least 4 weeks after their second COVID-19 vaccination had previously received two doses of an mRNA vaccine (BNT162b2 or mRNA-1273) maximum of 12 months after second vaccination If female and capable of bearing children – have a negative urine pregnancy test result at study entry and agree to employ adequate birth control measures for the duration of the study.
Exclusion criteria	Known allergies to vaccines previous infection with SARS-CoV-2 detectable anti-spike antibodies at the time of inclusion prior use of B-cell-depleting agents, such as rituximab Had grade 3 adverse effects from the mRNA vaccination reported Pregnancy and breast feeding Any other contraindication to any of the vaccine compounds.
Interventions
	Intervention 1 IM dose of either 30 mcg BNT16b2 or 100 mcg mRNA-1273, at least 28 days (mean 106) after 2 prime doses of BNT162b2 (89% of participants) or mRNA-1273 (11% of participants)
	Control 1 IM dose of 2.5x10^8 U of ChAdOx1(0.5mL), at least 28 days (mean 97) after 2 prime doses of BNT162b2 (89% of participants) or mRNA-1273 (11% of participants)
Participants
	Randomized 51 participants
	Characteristics of participants Type of participants: Immunosuppressed adults N=51 29 males Children: 0 Pregnant women: 0 Immunocompromized patients: 46 Mean age: Age range: NR
	Description of participants Immunosuppressed adults including elderly with no history of COVID-19 in a single centre in Austria.
Primary outcome
	In the register 1) Difference in SARS-CoV-2 antibody seroconversion rate by week 4 after vaccination boost at baseline between 3rd mRNA SARS-CoV-2 (Biontech/Pfizer or Moderna) and vector SARS-CoV-2 vaccine (AstraZeneca). 2) The efficacy of a 3rd mRNA boost vaccination in immunocompromised patients with inadequate humoral response (antibody titre <1500U/ml) to standard SARS-CoV-2 vaccination will be compared to low titre heathy controls by assessing the difference in antibody titre change before and after a second boost between the two groups.
	In the report Difference in SARS-CoV-2 spike antibody seroconversion rate between vector and mRNA vaccinated patients four weeks after the third dose. According to the manufacturer’s specification, seroconversion was defined as an anti-RBD antibody concentration of over 0.8 BAU/ml.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, Proposals must be submitted to the corresponding authors and will be reviewed within 2 months. Data accessibility: Source data of the main figures are provided as a source data file and in supplementary Table 5. De-identified participant data are available upon request. Proposals must be submitted to the corresponding authors and will be reviewed within 2 months. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement. Source data are provided with this paper. Corresponding authors: Leonhard X. Heinz (leonhard.heinz@meduniwien.ac.at) or Michael Bonelli (michael.bonelli@meduniwien.ac.at).
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Low
General comment	In addition to the published article and its supplement, the study registry and protocol were used in data extraction and risk of bias assessment. Recruitment was stopped early to allow timely completion, due to slowed inclusion rates from routine access to the additional vaccination dose being facilitated for high-risk patients in Austria. As a result, the target sample size (N=300) specified in the registry was not achieved. Some efficacy outcomes were not reported in the paper. There is no change from the trial registration in the intervention and control treatments.