Background incidence rates of selected adverse events of special interest (AESI) to monitor the safety of COVID-19 vaccines.

BACKGROUND: Determining background rates of medical conditions identified as adverse events of special interest (AESI) that may occur following COVID-19 vaccination is important for contextualising and investigating potential vaccine safety signals. METHODS: We conducted a retrospective population-based cohort study using linked emergency department, hospitalisation and death data for 2017 and 2018 from Australia's most populous state, New South Wales. Incident cases of select neurological conditions, arterial or venous thromboembolic conditions, secondary thrombocytopenia, myocarditis/pericarditis, and unique events of anaphylaxis and generalised convulsions were identified using internationally agreed upon diagnostic (ICD-10) codes. State-specific rates per 100,000 person-years were calculated, with further stratification by age group and sex where clinically relevant to the condition, and the number of expected cases nationally in one and 6 weeks was estimated. RESULTS: Background rates of selected neurological conditions were low with the exception of generalised convulsions for which 1,599-1,872 cases were estimated nationally in a 1-week period in the absence of vaccination. Using a narrow case definition, rates of Guillain-Barré Syndrome (3.9 per 100,000 person-years) were higher than international rates reported elsewhere. Thromboembolic and cerebral venous sinus thrombosis event rates increased with age. Myocarditis occurred more commonly in males, and was highest in males aged 18-24 years, with an estimated 1-4 cases expected nationally in a 1-week period. CONCLUSIONS: Using routinely collected linked healthcare data provides localised estimates of background rates of new onset or periodic AESI which enables rapid estimation of observed-versus-expected rates of events reported following COVID-19 vaccination. This Australian-specific analysis contributes AESI background rates which can be compared with those from other countries to enhance understanding of geographic variability in the frequency of specific AESI in the absence of vaccination, and can be utilised for signal detection during program implementation.

Safety of Four COVID-19 Vaccines across Primary Doses 1, 2, 3 and Booster: A Prospective Cohort Study of Australian Community Pharmacy Vaccinations.

Four COVID-19 vaccines are approved for use in Australia: Pfizer-BioNTech BNT162b2 (Comirnaty), AstraZeneca ChAdOx1 (Vaxzevria), Moderna mRNA-1273 (Spikevax) and Novavax NVX-CoV2373 (Nuvaxovid). We sought to examine adverse events following immunisation (AEFI) at days 3 and 42 after primary doses 1, 2, 3 and booster. We conducted active vaccine safety surveillance from 130 community pharmacies in Australia integrated with AusVaxSafety, between August 2021-April 2022. Main outcomes: AEFI at 0-3 days post-vaccination; medical review/advice at 3 days and 42 days post-vaccination; SARS-CoV-2 breakthrough infection by day 42. Of 110,024 completed day 3 surveys (43.6% response rate), 50,367 (45.8%) reported any AEFI (highest proportions: Pfizer 42%, primary dose 3; AstraZeneca 58.3%, primary dose 1; Moderna 65.4% and Novavax 58.8%, both primary dose 2). The most common AEFI reported across all doses/vaccines were local reactions, systemic aches and fatigue/tiredness. Overall, 2172/110,024 (2.0%) and 1182/55,329 (2.1%) respondents sought medical review at days 3 and 42, respectively, and 931/42,318 (2.2%) reported breakthrough SARS-CoV-2 infection at day 42. We identified similar AEFI profiles but at lower proportions than previously reported for Pfizer, AstraZeneca, Moderna and Novavax COVID-19 vaccines. Moderna vaccine was the most reactogenic and associated with higher AEFI proportions across primary doses 2, 3, and booster.

Surveillance of adverse events following immunisation in Australia annual report, 2020.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.

The short term safety of COVID-19 vaccines in Australia: AusVaxSafety active surveillance, February - August 2021.

OBJECTIVE: To assess the short term safety of the COVID-19 vaccines Comirnaty (Pfizer-BioNTech BNT162b2) and Vaxzevria (AstraZeneca ChAdOx1) in Australia. DESIGN: Prospective observational cohort study; online surveys by AusVaxSafety, a national active vaccine safety surveillance system, three and eight days after vaccination. SETTING, PARTICIPANTS: People aged 16 years or more who received COVID-19 vaccines at sentinel vaccination hubs, general practices, or Aboriginal Community Controlled Health Organisation clinics, 22 February - 30 August 2021. MAIN OUTCOME MEASURES: Primary outcome: proportion of respondents who reported any adverse event following immunisation (AEFI) 0-3 days after vaccination. SECONDARY OUTCOMES: proportions of respondents who reported specific adverse events or medical review for AEFI within seven days of vaccination; impact on usual daily activities; recovery. RESULTS: 4 851 480 people received COVID-19 vaccines at participating sentinel sites during the study period (25% of all COVID-19 vaccine doses administered in Australia to 30 August 2021). 3 035 983 people responded to both surveys (response rate, 62.6%); 35.9% of respondents reported one or more AEFI 0-3 days after Comirnaty dose 1, 54.7% after Comirnaty dose 2, 52.8% after Vaxzevria dose 1, and 22.0% after Vaxzevria dose 2. Local pain, fatigue, headache, and myalgia were the most frequently reported symptoms. After adjusting for demographic characteristics, vaccination site type, jurisdiction, and self-reported medical conditions, the odds of reporting any AEFI were higher for women than men (range of adjusted odd ratios [aORs], by vaccine and dose, 1.53-1.84), for people with a history of anaphylaxis (aOR range, 1.28-1.45), and for people reporting certain underlying conditions, including obesity (aOR range, 1.15-1.75), immunodeficiency (aOR range, 1.04-2.24), or chronic inflammatory disease (aOR range, 1.05-1.75). 0.9% of respondents sought medical advice in the three days following vaccination, most frequently after Comirnaty dose 2 (1.4%) and Vaxzevria dose 1 (1.2%). CONCLUSION: AusVaxSafety active surveillance affirms the short term safety profile of Comirnaty and Vaxzevria vaccines in a large population sample during the first six months of the Australian COVID-19 vaccination program.

Usability, acceptability, and feasibility of a High-Density Microarray Patch (HD-MAP) applicator as a delivery method for vaccination in clinical settings.

BACKGROUND: High-density microarray patch (HD-MAP) vaccines may increase vaccine acceptance and use. We aimed to ascertain whether professional immunizers (PIs) and other healthcare workers (HCWs) in Australia, a High-Income Country (HIC), found the HD-MAP applicator usable and acceptable for vaccine delivery. METHODS: This feasibility study recruited PIs and HCWs to administer/receive simulated HD-MAP administration, including via self-administration. We assessed usability against essential and desirable criteria. Participants completed a survey, rating their agreement to statements about HD-MAP administration. A subset also participated in an interview or focus group. Survey data were analyzed using descriptive statistics, and interviews were transcribed and subject to thematic analysis. RESULTS: We recruited 61 participants: 23 PIs and 38 HCWs. Findings indicated high usability and acceptability of HD-MAP use across both groups by a healthcare professional or trained user and for self-administration with safety measures in place. Most administrations met essential criteria, but PIs, on average, applied the HD-MAP for slightly less time than the required 10-seconds, which the HCWs achieved. PIs perceived safety concerns about home administration but found layperson self-administration acceptable in an emergency, pandemic, and rural or remote settings. CONCLUSIONS: Participants found HD-MAP administration usable and acceptable. Usability and acceptability are likely to be improved through end-user education and training.

Professional immunizers and healthcare workers found high-density microarray patch devices highly usable and acceptable to administer vaccines.HD-MAPs may have advantages over intramuscular injections in clinical settings and in pandemics.Vaccination with HD-MAP may improve acceptance for those with needle-related anxiety.

Household transmission of COVID-19 in 2020 in New South Wales, Australia.

Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study examines factors associated with transmission among cases diagnosed with coronavirus disease 2019 (COVID-19) and their household contacts, in New South Wales (NSW), Australia, during July-October 2020. A register of all laboratory-confirmed COVID-19 cases was used to extract demographic and clinical information for cases and household contacts. Secondary attack rates (SARs) among household members were calculated and generalised estimating equations were used to estimate risks of transmission in relation to various characteristics of the primary case and the household contacts. In total, 229 households were included; they consisted of 229 primary cases and 659 close contacts. The overall household SAR was 22.5% (148/659). After adjusting for symptoms, age and sex of primary case, spouse status of household contacts and household size, the odds of secondary transmission were lower in primary cases who were asymptomatic at diagnosis than in symptomatic cases (odds ratio, OR: 0.13; 95% confidence interval (95% CI): 0.04-0.48); and higher in primary cases aged 60 years and over than in those aged 19-39 years (OR: 3.45; 95% CI: 1.53- 7.75). Being a spouse of the primary case was also associated with increased transmission compared to non-spouses (OR: 1.93; 95% CI: 1.24-3.02). After adjustments, there was no significant effect on transmission of the primary case's sex, or of the number of people in the household. This study documents demographic and clinical characteristics that increase transmission rates in households in the period prior to the introduction of SARS-CoV-2 variants. These data can be used as a baseline from which to compare household transmission in outbreaks dominated by new variants.

Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series.

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.

Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study.

BACKGROUND: School closures have occurred globally during the COVID-19 pandemic. However, empiric data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and in educational settings are scarce. In Australia, most schools have remained open during the first epidemic wave, albeit with reduced student physical attendance at the epidemic peak. We examined SARS-CoV-2 transmission among children and staff in schools and early childhood education and care (ECEC) settings in the Australian state of New South Wales (NSW). METHODS: Laboratory-confirmed paediatric (aged ≤18 years) and adult COVID-19 cases who attended a school or ECEC setting while considered infectious (defined as 24 h before symptom onset based on national guidelines during the study period) in NSW from Jan 25 to April 10, 2020, were investigated for onward transmission. All identified school and ECEC settings close contacts were required to home quarantine for 14 days, and were monitored and offered SARS-CoV-2 nucleic acid testing if symptomatic. Enhanced investigations in selected educational settings included nucleic acid testing and SARS-CoV-2 antibody testing in symptomatic and asymptomatic contacts. Secondary attack rates were calculated and compared with state-wide COVID-19 rates. FINDINGS: 15 schools and ten ECEC settings had children (n=12) or adults (n=15) attend while infectious, with 1448 contacts monitored. Of these, 633 (43·7%) of 1448 had nucleic acid testing, or antibody testing, or both, with 18 secondary cases identified (attack rate 1·2%). Five secondary cases (three children; two adults) were identified (attack rate 0·5%; 5/914) in three schools. No secondary transmission occurred in nine of ten ECEC settings among 497 contacts. However, one outbreak in an ECEC setting involved transmission to six adults and seven children (attack rate 35·1%; 13/37). Across all settings, five (28·0%) of 18 secondary infections were asymptomatic (three infants [all aged 1 year], one adolescent [age 15 years], and one adult). INTERPRETATION: SARS-CoV-2 transmission rates were low in NSW educational settings during the first COVID-19 epidemic wave, consistent with mild infrequent disease in the 1·8 million child population. With effective case-contact testing and epidemic management strategies and associated small numbers of attendances while infected, children and teachers did not contribute significantly to COVID-19 transmission via attendance in educational settings. These findings could be used to inform modelling and public health policy regarding school closures during the COVID-19 pandemic. FUNDING: NSW Government Department of Health.