Kristine K. Macartney

Background: We aimed to describe the clinical spectrum and burden of COVID-19-associated neurologic disease in Australian children. Methods: We extracted Australian national sentinel site surveillance data on COVID-19-associated neurologic disease in children hospitalized in the Paediatric Active Enhanced Disease Surveillance network, 2020-2023. Neurologic complications included encephalitis, encephalopathy, Guillain-Barre syndrome, seizures and cerebrovascular accident among others. We calculated the proportion of hospitalized pediatric COVID-19 cases associated with neurologic disease and described the spectrum of presentations including clinical features and severity. We calculated incidence rates of neurologic disease within COVID-19 variant eras among hospitalized patients. Results: We identified 311 cases of SARS-CoV-2 infection with neurologic disease among 4616 hospitalized pediatric cases of COVID-19 reported through the surveillance network, representing 5.3 cases per 100 pediatric COVID-19 admissions. The most common COVID-19-associated neurologic presentations were seizures (n = 215), including febrile seizures. Nonspecific encephalopathy (n = 62), encephalitis, Guillain-Barre Syndrome, acute cerebellar syndromes, acute demyelinating encephalomyelitis and cerebrovascular accident were also reported. Almost 60% of children were ≤4 years, approximately 30% had pre-existing neurologic conditions and almost half had other medical comorbidities. COVID-19-associated neurologic complications infrequently led to death, although 25% (n = 2/8) of children with COVID-19 encephalitis died. The incidence rate of COVID-19-associated neurologic disease was lowest during the late Omicron era. Conclusions: Neurologic complications among COVID-19 hospitalized children are relatively frequent. While most neurologic complications are transient, including seizures, encephalitis remains a cause of significant morbidity. Children with pre-existing neurologic disease and other comorbidities are at higher risk.

Background: Vaccination against SARS-CoV-2 was a crucial public health measure during the COVID-19 pandemic. Among the multiple strategies developed to increase vaccine uptake, governments often employed vaccine mandates. However, little evidence exists globally about the impact of these mandates and their subsequent removal on vaccine uptake, including in Australia, France, Italy and the USA. The aim of this study is to provide a protocol to evaluate and quantify the impact of COVID-19 vaccine mandates and removals on vaccine uptake in these countries, with a specific focus on comparing Australian policies with those from Europe and the USA. Actualising the work outlined in this protocol will help to provide policy and technical guidance for future pandemic preparedness and routine immunisation programmes. Methods: This protocol outlines a retrospective study using existing data sources including Australian Immunisation Register-Person Level Integrated Data Asset for Australia and publicly available data for France, Italy and California (USA). Causal inference methods such as interrupted time series, regression discontinuity design, difference-in-differences, matching and synthetic control will be employed to assess the estimated effects of vaccine mandates and removals on vaccine uptake. Background: The University of Newcastle's human research ethics committee has approved the study (reference number: H-2024-0160). Peer-reviewed papers will be submitted, and results will be presented at public health, immunisation and health economic conferences nationally and internationally. A lay summary will be published on the MandEval website.

Background: The association between Guillain-Barré syndrome (GBS) and certain COVID-19 vaccines is inconclusive. We investigated the risk of GBS after COVID-19 vaccination or SARS-CoV-2 infection. Methods: Using a common protocol, we conducted a self-controlled case series study from 1 December 2020 to 9 August 2023 at 20 global sites within the Global Vaccine Data Network™ (GVDN®). Brighton Collaboration case definition criteria were used to determine the level of certainty (LOC) of medical record-reviewed GBS cases at 15 sites. GBS cases following SARS-CoV-2 infection were identified from electronic data sources (EDS) from 11 sites. We estimated the relative incidence (RI) of GBS within 1-42 days following receipt of adenoviral vector, mRNA, or inactivated COVID-19 vaccines or SARS-CoV-2 infection using conditional Poisson regression models, controlling for seasonality. We used random effects meta-analysis to pool the estimates across sites. Results: Of 410 medical record-reviewed post-vaccination GBS cases (out of 2086 EDS-identified cases), 49 were LOC 1 or 2, 187 were LOC 3 or 4, and 174 were LOC 5. These cases received a total of 794 doses of COVID-19 vaccines (160 [20 %] adenoviral vector vaccine doses, 556 [70 %] mRNA vaccine doses, 77 [10 %] inactivated vaccine doses, and 1 [0.1 %] protein-based vaccine dose) during the observation period. We observed an increased risk of confirmed (LOC 1-2) GBS after receiving ChAdOx1-S/nCoV-19 (Vaxzevria/Covishield) (RI = 3.10; 95 % confidence interval [CI], 1.12-8.62). Decreased risks of LOC 1-4 GBS were observed after receiving BNT162b2 (Comirnaty/Tozinameran) (RI = 0.48; 95 %CI, 0.27-0.85) and CoronaVac/Sinovac (RI = 0.04; 95 %CI, 0.00-0.61). For 489 EDS-identified GBS cases after SARS-CoV-2 infection, we found GBS risk to be increased (RI = 3.35; 95 %CI, 1.83-6.11). Conclusions: In this large multinational study, we found increased risks of GBS within 42 days after Vaxzevria/Covishield vaccination or SARS-CoV-2 infection, and decreased risks after receiving Comirnaty/Tozinameran or CoronaVac/Sinovac COVID-19 vaccines.

High quality Indigenous status data for vaccine preventable diseases (VPDs) in the National Notifiable Diseases Surveillance System (NNDSS) is important for evaluation of immunisation programs and ultimately for improving health outcomes for Aboriginal and Torres Strait Islander peoples. We evaluated Indigenous status completeness, and factors influencing it, for VPDs in the NNDSS. Literature review (published and grey); descriptive analysis of NNDSS data for selected VPDs over the 2010-2019 period; standardised online survey (containing closed- and open-ended questions) of key informants; semi-structured follow-up interviews. National level Indigenous status completeness for those VPDs with a Communicable Diseases Network Australia (CDNA) target of 95% was above that target for Haemophilus influenzae type b, measles, invasive meningococcal disease and invasive pneumococcal disease (IPD: < 5 and ≥ 50 years); and was within four percentage points for hepatitis A, newly acquired hepatitis B and pertussis (< 5 years). For VPDs with an 80% target, completeness was ≥ 90% for diphtheria, mumps, rubella and tetanus; ≥ 80% for IPD (≥ 5 to < 50 years); and below target for unspecified hepatitis B (54%), laboratory confirmed influenza (47%), pertussis (≥ 5 years; 60%) and rotavirus (71%). However, completeness was above 90% for all VPDs in the Northern Territory, and all except laboratory confirmed influenza (89%) in Western Australia. Key barriers to Indigenous status completeness include the absence of an Indigenous status field on most pathology request forms and limited public health authority resource capacity to follow up missing data, particularly for high incidence diseases. National level Indigenous status completeness is high for most VPDs but low for others, particularly for high incidence diseases predominantly notified by laboratories. Completeness is uniformly high for all VPDs in the Northern Territory and Western Australia; however, this is due to the resource-intensive public health follow-up of all notifications and manual cross-checking of other databases when Indigenous status is missing. To more efficiently optimise Indigenous status completeness in the NNDSS across all jurisdictions, a mix of additional strategies is needed to ensure accurate identification and recording in primary care, hospital, laboratory and public health settings, and effective transfer between them.

Background: Management and outcomes of children hospitalised with acute SARS-CoV-2 infection may differ throughout the pandemic or with admission type (clinical COVID-19, incidental COVID-19 or nosocomial infection). Objective: Describe the severity, management and outcomes of hospitalised children with acute SARS-CoV-2 infection in Australia across the first 4 years of the pandemic and compare between admission types, SARS-CoV-2 variants, age groups and immune status. Methods: A multi-centre prospective cohort study of 6009 children aged 0-16 years between January 2020 and June 2023. Results: Most children (84.3 %) did not receive respiratory support, 33.4 % received antibiotics and 8 % were admitted to intensive care unit (ICU). Infants <6 months old were more likely to be admitted with clinical COVID than older children (12-16 years). Older children were more likely to receive antibiotics (27.8 % vs 43.9 %), corticosteroids (11.3 % vs 34.1%) or ICU admission (5.2 % vs 13.5 %). Compared to immunocompetent children, the immunosuppressed (7.7 %) were more likely to have nosocomial infection (9.5 % vs 3.9 %), receive antibiotics (57 % vs 25 %) or antivirals (18 % vs 4.4 %), but less likely to require respiratory support (93.4 % vs 83.8 %) or ICU admission (3.5 % vs 8 %). Children with nosocomial SARS-CoV-2 infection had higher rates of invasive ventilation (8 %) and ICU admission (21 %) compared to those with clinical (2.1 % and 7.1 % respectively) or incidental COVID-19 (4.8 % and 9.1 % respectively). Conclusions: Acute COVID-19 generally caused mild disease in hospitalised children, with management and outcomes differing by age and admission type. Similar outcomes were observed across the pandemic. Nosocomial SARS-CoV-2 infection was associated with more severe disease.