Surveillance of adverse events following immunisation in Australia annual report, 2021.

Abstract: Annual seasonal influenza epidemics cause substantial disease and economic burden worldwide. During the coronavirus disease 2019 (COVID-19) pandemic in 2020 and 2021, influenza activity significantly declined. However, influenza resurged in Australia following the relaxation of non-pharmaceutical interventions, with increased influenza virus circulation in early 2022 coinciding with the SARS-CoV-2 Omicron BA.2 variant wave. Together with other respiratory virus diseases, these disease impacts on the Australian population and healthcare system have re-emphasised the importance of influenza vaccination and control. We aim to provide an overview of the current seasonal influenza vaccination program in Australia and summarise evidence and considerations underpinning potential future immunisation strategies. Influenza causes disproportionately higher morbidity and mortality in young children and older adults. Other populations at elevated risk from influenza include Aboriginal and Torres Strait Islander peoples, pregnant women, and people with certain underlying medical conditions. All Australians aged ≥ 6 months are recommended to receive influenza vaccine every year. The National Immunisation Program (NIP) provides free vaccine for eligible at-risk populations. While approximately 70% of older adults had received influenza vaccine in 2022, coverage in other age groups remains suboptimal. There are several key unmet needs and challenges, but also potential strategies for enhancing the influenza vaccination program in Australia. Improved monitoring and evaluation, including the use of relevant linked datasets for such purposes, is imperative to better understand variations in coverage and vaccination impact in specific populations. Adoption of evidence-based strategies, such as culturally appropriate resources that consider the characteristics of diverse Australian populations, may also help to achieve higher vaccine coverage rates. Additionally, greater vaccine uptake across the population could be facilitated by expanding the NIP-eligible population where cost-effective, and adopting the use of more effective and different types of vaccines when available.

Letter to the Editor: A comparison of post-COVID vaccine myocarditis classification using the Brighton Collaboration criteria versus (United States) Centers for Disease Control criteria: an update.

Abstract: (No abstract provided).

Audiovestibular adverse events following COVID-19 vaccinations.

INTRODUCTION: Evidence regarding audiovestibular adverse events post COVID-19 vaccination to date has been inconclusive regarding a potential association. This study aimed to determine if there was an increase in audiovestibular events following COVID-19 vaccination in South-eastern Australia during January 2021-March 2023. METHODS: A multi-data source approach was applied. First, a retrospective observational analysis of spontaneous reports of audiovestibular events to a statewide vaccine safety surveillance service, SAEFVIC. Second, a self-controlled case series analysis using general practice data collected via the POpulation Level Analysis and Reporting (POLAR) tool. RESULTS AND CONCLUSIONS: This study is the first to demonstrate an increase in general practice presentations of vertigo following mRNA vaccines (RI = 1.40, P <.001), and tinnitus following both the Vaxzevria® adenovirus vector and mRNA vaccines (RI = 2.25, P <.001 and 1.53, P <.001 respectively). There was no increase in hearing loss following any COVID-19 vaccinations. Our study, however, was unable to account for the potential of concurrent COVID-19 infections, which literature has indicated to be associated with audiovestibular events. Healthcare providers and vaccinees should be alert to potential audiovestibular complaints after COVID-19 vaccination. Our analysis highlights the importance of using large real-world datasets to gather reliable evidence for public health decision making.

Emergency department presentations for chest complaints after mRNA COVID-19 vaccinations in children and adolescents.

OBJECTIVE: To investigate characteristics and management of children presenting with chest complaints to a tertiary paediatric ED post-mRNA COVID-19 vaccine. METHODS: This was a retrospective medical record review with data linkage to the Australian Immunisation Register. The study setting was the Royal Children's Hospital, Melbourne, Australia. Children <18 years who had a troponin blood test performed in hospital within 14 days of receiving mRNA COVID-19 vaccination were included. Elevated troponin and myocarditis or pericarditis as per Brighton criteria was the primary outcome. Vaccination status, length of stay, investigations and clinical management were secondary outcomes. RESULTS: Six hundred and ten patients had a troponin test in 13 months. After exclusion of trauma-related tests (n = 31), known cardiac patients (n = 75) and others (n = 145), 359 troponins were obtained due to chest complaints and related symptoms, with 283 troponins assessed to be mRNA vaccination-related. There was a temporal peak in presentations with a 30-fold monthly increase in troponin post-commencement of mRNA COVID-19 vaccines. In those with chest complaints following mRNA vaccination, mean age was 14 years and 50.4% were female. Fourteen out of 283 (5%) vaccine-related troponins were abnormal with 14 patients assessed to have vaccine-associated myocarditis. No patients had pericarditis. CONCLUSIONS: There was a large number of possible mRNA COVID-19 vaccine-related chest complaints presenting to the ED. Few patients had abnormal troponins or myocarditis.

Long term follow up and outcomes of Covid-19 vaccine associated myocarditis in Victoria, Australia: A clinical surveillance study.

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.

Analyzing an immunization resource website: User browsing trends.

PURPOSE: Access to internet-based resources may help to improve population health awareness and literacy surrounding immunization related topics. The primary aim of this study was to evaluate and analyze trends for a single immunization resource website, the Melbourne Vaccine Education Centre (MVEC). PRINCIPAL RESULTS: Over a four-year period from 2019 to 2022, the website had over 2 million visitors from 236 countries. Users were predominantly female, in the 25 to 44 year age bracket and accessed resources using a mobile device. There was significant interest in specific vaccine related topics, particularly during the COVID-19 pandemic, that corresponded with key vaccine related recommendations and updates from a national level. Usage patterns saw spikes in interest around topics including COVID-19 vaccine administration techniques and adverse events following immunization. MAJOR CONCLUSIONS: Use of online platforms including websites such as MVEC may reflect trends and behaviors towards immunization related information. Analysis of usage patterns have provided user insights into key domains of interest including areas such as vaccine administration, policies and programs, vaccine safety and barriers to vaccine uptake.

ATAGI 2023 Annual Statement on Immunisation.

The Australian Technical Advisory Group on Immunisation (ATAGI) 2023 Annual Statement on Immunisation is the third publication in this series. It highlights the key successes, trends and challenges in the use of vaccines and control of vaccine preventable diseases (VPDs) in Australia in 2022. It also signals ATAGI's priority actions for addressing key issues for 2023 and beyond.

The clinicopathological features of thrombosis with thrombocytopenia syndrome following ChAdOx1-S (AZD1222) vaccination and case outcomes in Australia: a population-based study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) associated with viral vector COVID-19 vaccines, including ChAdOx1-S (AstraZeneca AZD1222) vaccine, can result in significant morbidity and mortality. We report the clinicopathological features of TTS following ChAdOx1-S vaccination and summarise the case outcomes in Australia. Methods: In this cohort study, patients diagnosed with TTS in Australia between 23 March and 31 December 2021 were identified according to predefined criteria. Cases were included if they met the Therapeutic Goods Administration (TGA) probable and confirmed case definitions and were reclassified using Centres for Disease Control and Prevention (CDC) definition for analysis. Data were collected on patient baseline characteristics, clinicopathological features, risk factors, treatment and outcomes. Findings: A total of 170 TTS cases were identified, with most occurring after the first dose (87%) of ChAdOx1-S. The median time to symptom onset after vaccination and symptom onset to admission was 11 and 2 days respectively. The median age of cases was 66 years (interquartile range 55-74). All except two patients received therapeutic anticoagulation and 66% received intravenous immunoglobulin. Overall, 85.3% of cases were discharged home after a median hospitalisation of 6 days, 9.4% required ongoing rehabilitation and 5.3% died. Eight deaths were related to TTS, with another dying from an unrelated condition while receiving treatment for TTS. Deaths occurred more commonly in those classified as Tier 1 according to the CDC definition and were associated with more severe thrombocytopenia and disease-related haemorrhage. Interpretation: TTS, while rare, can be severe and have catastrophic outcomes in some individuals. In Australia, the mortality rate was low compared to that reported in other high-income countries. Almost all received therapeutic anticoagulation with no bleeding complications and were successfully discharged. This emphasises the importance of community education and an established pathway for early recognition, diagnosis and treatment of TTS. Funding: Australian Commonwealth Department of Health and Aged Care. H.A Tran, N. Wood, J. Buttery, N.W. Crawford, S.D. Chunilal, V.M. Chen are supported by Medical Research Future Funds (MRFF) grant ID 2015305.

International Pediatric COVID-19 Severity Over the Course of the Pandemic.

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Safety of BCG vaccination and revaccination in healthcare workers.

BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

Erratum: Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15241.].

Considerations for vaccinating children against COVID-19.

COVID-19 vaccines have been introduced in children and adolescents in many countries. However, high levels of community transmission and infection-derived immunity make the decision to introduce COVID-19 vaccination of children in countries yet to do so particularly challenging. For example, other vaccine preventable diseases, including measles and polio, generally have far higher childhood morbidity and mortality in low-income and middle-income countries (LMICs) than COVID-19, and coverage with these vaccines has declined during the pandemic. Many countries are yet to introduce pneumococcal conjugate and rotavirus vaccines for children, which prevent common causes of childhood death, or human papillomavirus vaccine for adolescents. The Pfizer and Moderna COVID-19 vaccines that have been widely tested in children and adolescents have a positive risk-benefit profile. However, the benefit is less compared with other life-saving vaccines in this age group, particularly in LMICs and settings with widespread infection-derived immunity. The resources required for rollout may also pose a considerable challenge in LMICs. In this paper, we describe COVID-19 in children, with a focus on LMICs, and summarise the published literature on safety, efficacy and effectiveness of COVID-19 vaccination in children and adolescents. We highlight the complexity of decision-making regarding COVID-19 vaccination of children now that most of this low-risk population benefit from infection-derived immunity. We emphasise that at-risk groups should be prioritised for COVID-19 vaccination; and that if COVID-19 vaccines are introduced for children, the opportunity should be taken to improve coverage of routine childhood vaccines and preventative healthcare. Additionally, we highlight the paucity of epidemiological data in LMICs, and that for future epidemics, measures need to be taken to ensure equitable access to safe and efficacious vaccines before exposure to infection.

Corrigendum to "Lower risk of multi-system Inflammatory Syndrome in Children (MIS-C) with the Omicron variant" [The Lancet Regional Health - Western Pacific 27 (2022) 100604].

[This corrects the article DOI: 10.1016/j.lanwpc.2022.100604.].

COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020-2022.

Background: COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic. Methods: Data reported to the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia, across 49 ICUs from February 2020 to June 2022 were extracted. We defined 'child' as patients aged <12 years, 'adolescent' as patients aged 12-17 years, and 'young adult' as patients aged 18-25 years. Findings: We identified 226 paediatric ICU admissions with COVID-19, representing 3.9% of ICU admissions across the study period. Comorbidity was present in 34.6% of children, 51.4% of adolescents, and 48.7% of young adults. The need for respiratory support was highest in young adults. While 28.3% of patients <18 years required invasive ventilation, in-hospital mortality in paediatric patients was 3.6%. During the Omicron period, there was an increase in the annualised incidence of age-specific COVID-19 ICU admissions per 100,000 population, albeit a decrease in the incidence per 1000 SARS-CoV-2 notifications. Interpretation: This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications. Funding: SPRINT-SARI Australia is supported by the Department of Health, Commonwealth of Australia [Standing Deed SON60002733].

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

A novel anterior nasal swab to detect respiratory viruses: a prospective study of diagnostic accuracy.

Detection of respiratory viruses requires testing of the upper respiratory tract to obtain specimens for analysis. However, nasal and throat swabs can cause discomfort and procedural anxiety in children. Respiratory sampling methods which are accurate and less invasive are needed. We aim to determine the positive and negative percentage agreement of a novel anterior nasal swab (ANS) compared with the combined throat and anterior nasal swab (CTN), the reference standard, for detection of respiratory viruses. Children 5 - 18 years of age presenting to a tertiary paediatric hospital with respiratory symptoms were tested with both swabs in randomised order. Respiratory samples were tested on a multiplex RT-PCR panel. Viral detections, RT-PCR cycle-threshold values and child/parent/clinician experience of the swab were recorded. There were 157 viral detections from 249 participant CTN swabs. In comparison with the CTN, the overall positive and negative percentage agreement of ANS for detection of respiratory viruses was 96.2% (95% CI, 91.8-98.3%) and 99.8% (95% CI, 99.6-99.9%), respectively. The ANS was "extremely comfortable", or only a "little uncomfortable" for 90% of children compared with 48% for CTN. 202 children (84%) rated the ANS as the preferred swab, and 208 (87%) indicated they would prefer ANS for future testing. The ANS required additional laboratory handling processes compared to the CTN. The ANS has high positive percentage agreement and is comparable to the current standard of care. The high acceptability from the less invasive ANS provides a more comfortable method for respiratory virus testing in children.Trial registrationClinicalTrials.gov ID NCT05043623.

ATAGI Targeted Review 2021: the national COVID-19 vaccination program.

Abstract: The overarching goal of the Australian coronavirus disease 2019 (COVID-19) vaccination program has been to protect all people in Australia from the harm caused by the novel coronavirus SARS-CoV-2. This review reflects on the role of the Australian Technical Advisory Group on Immunisation (ATAGI) in the national COVID-19 vaccination program, in terms of the initial programmatic and clinical recommendations in the evolving context of evidence relating to the disease and vaccines, epidemiology, and the program rollout. To fulfil the obligation to provide evidence-based advice to the Minister for Health and Aged Care on the safe, effective and equitable use of COVID-19 vaccines, ATAGI has worked closely with other agencies and committees such as the Therapeutic Goods Administration (TGA) and the Communicable Diseases Network Australia. ATAGI recommendations have sought to optimise the use of the available vaccine doses in achieving the objectives of preventing serious illness and death from COVID-19 while addressing any emerging safety signals following program commencement on 22 February 2021. As of mid-November 2021, the use of COVID-19 vaccines in children aged 5 to 11 years was being considered by the TGA and ATAGI; and emerging evidence, in areas such as use of heterologous vaccine schedules and co-administration with other vaccines, was under review. Despite unprecedented challenges which the delivery of mass COVID-19 vaccination presented to health systems globally, in Australia much was achieved in 2021 with over 90% coverage for primary doses in the vaccine-eligible population. Evaluation, using high quality data and assessment methods, of vaccination program outcomes-such as coverage, vaccine effectiveness and impact-is key to determine whether program objectives have been achieved and where gaps remain. Reflecting on the lessons learned so far would help further improve the national COVID-19 vaccination program and would also benefit programs for other routine vaccines and planning for future pandemics.