Real world Nuvaxovid COVID-19 vaccine safety profile after 100,000 doses in Australia, 2022-2023

Introduction Nuvaxovid became available in Australia from February 2022, a year later than the first COVID-19 vaccines were released. It was a much-anticipated alternative vaccine for people that had either suffered an adverse event to–and/or were hesitant to receive–one of the mRNA or adenovirus-based COVID-19 vaccines. Although safety from clinical trials was reassuring, small trial population size, relatively low administration rates worldwide and limited post-licensure intelligence meant potential rare adverse events were underinformed. Methods We conducted a retrospective observational analysis of adverse events following immunisation (AEFI) spontaneously reported to SAFEVAC, the integrated vaccine safety surveillance system used by Victoria and Western Australia, Australia. Reports received from 14 Feb 2022 to 30 June 2023 were analysed by vaccinee demographics, reported reactions and COVID-19 vaccine dose received and compared as reporting rates (RR) per 100,000 doses administered. Results 356 AEFI reports were received, following 102,946 Nuvaxovid doses administered. Rates were higher post dose 1 than dose 2 (rate ratio 1.5, p=0.0008); primary series than booster (rate ratio 2.4, p<0.0001); in females than males (rate ratio 1.4, p<0.01), especially those aged 30-49 years (RR=1.6, p=0.002). Serious AEFI included 76 chest pain (RR=73.8), two myocarditis (RR=1.9) and 20 pericarditis (RR=19.4). No cases of Guillain-Barré or thrombosis with thrombocytopaenia syndromes were reported and no deaths attributable to vaccination. Conclusion The shared SAFEVAC platform enables pooling of clinically reviewed data across jurisdictions, increasing the safety profile evidence-base of novel vaccines like Nuvaxovid and improving the odds for identification and description of rare events across all vaccines. #### Key public health message ##### What did you want to address in this study and why? What did you want to address in this study and why? Nuvaxovid is a protein-based vaccine for protection against COVID-19. Nuvaxovid received provisional licensure following clinical trials in which 30,058 participants received at least one dose of Nuvaxovid. Introduced following adenoviral vector and mRNA COVID-19 vaccines, some people had been waiting for this vaccine as an alternative to other brands that had risk of blood clots or heart inflammation. We wanted to inform on safety of Nuvaxovid following over 100,000 doses administered in real-world population-wide setting in two Australian states. ##### What have we learnt from this study? What have we learnt from this study? Adverse events reported were mostly mild, transient symptoms and no deaths were attributed to Nuvaxovid immunisation. Reporting rate for heart inflammation was similar to the mRNA COVID-19 vaccines, but more likely to be milder pericarditis than myocarditis. For over 25,000 people Nuvaxovid was their first dose of a COVID-19 vaccine received, despite being more than a year since COVID-19 vaccines became available. ##### What are the implications of your findings for public health? What are the implications of your findings for public health? This first real-world population-wide evidence of Nuvaxovid vaccine safety provides reassurance on the risk-benefit of vaccination for protection from severe COVID-19 disease. We must continue to look hard, using real-world data, to not only ensure vaccines are safe, but also support confidence in immunisation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Department of Health Victoria funds Murdoch Children's Institute to host and manage SAFEVAC for delivery of vaccine safety services in Victoria. The Department of Health Victoria has no access to data or role in analysis, writing or approval to publish. In WA this work is conducted as part of vaccine safety surveillance under the Public Health Act by WA public health servants. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this study was provided in Victoria as use of a registered database 36219 for public health surveillance and by the Chief Health Officer WA for provision of de-identified aggregated data informing public health surveillance. Permission to publish data from the Australian Immunisation Register was granted by Australian Government Department of Health and Aged Care. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Personal health data are held in confidence by the respective jurisdictional governance bodies and can only be released in accordance with ethics committee approvals. Aggregate summary data are publicly available weekly online in Victoria and annually for both Victoria and Western Australia.