Differential COVID-19 case ascertainment by age and vaccination status in Victoria, Australia: a serosurveillance and record linkage study.

Objectives: To compare serological evidence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with linked coronavirus disease 2019 (COVID-19) case notification data in Victoria, Australia, and to determine in vitro SARS-CoV-2 neutralisation activity based on prior infection and vaccination history. Design, setting, participants: Four cross-sectional serological surveys were conducted between 30 June and 31 October 2022 (a period of Omicron BA.4/BA.5 dominance) using 1,974 residual serum samples obtained from the Victorian Infectious Diseases Reference Laboratory. Serological results were linked to COVID-19 case notification and vaccination data. Surrogate virus neutralisation testing was performed to obtain in vitro inhibition estimates by anti-nucleocapsid serostatus and COVID-19 vaccination history. Main outcome measures: Adjusted anti-SARS-CoV-2 spike and nucleocapsid seropositivity by sex, age and region of residence; adjusted proportion of cases notified by anti-nucleocapsid serostatus, age and number of COVID-19 vaccination doses received; adjusted percentage in vitro inhibition against wildtype and Omicron BA.4/BA.5 SARS-CoV-2 variants by anti-nucleocapsid serostatus and COVID-19 vaccination history. Results: The prevalence of anti-SARS-CoV-2 nucleocapsid antibodies was inversely proportional to age. In October 2022, prevalence was 84% (95% confidence interval [95% CI]: 75-93%) among 18-29-year-olds, compared to 39% (95% CI: 27-52%) among ≥ 80-year-olds. In most age groups, approximately 40% of COVID-19 cases appear to have been notified via existing surveillance mechanisms. Case notification was highest among individuals older than 80 years and people who had received COVID-19 vaccine booster doses. In vitro neutralisation of Omicron BA.4/BA.5 sub-variants was highest for individuals with evidence of both prior infection and booster vaccination. Conclusions: Under-notification of SARS-CoV-2 infections in the Victorian population is not uniform across age and vaccination strata. Seroprevalence data that give insights into case notification behaviour provide additional context for the interpretation of existing COVID-19 surveillance information.

Individual variation in vaccine immune response can produce bimodal distributions of protection.

The ability for vaccines to protect against infectious diseases varies among individuals, but computational models employed to inform policy typically do not account for this variation. Here we examine this issue: we implement a model of vaccine efficacy developed in the context of SARS-CoV-2 in order to evaluate the general implications of modelling correlates of protection on the individual level. Due to high levels of variation in immune response, the distributions of individual-level protection emerging from this model tend to be highly dispersed, and are often bimodal. We describe the specification of the model, provide an intuitive parameterisation, and comment on its general robustness. We show that the model can be viewed as an intermediate between the typical approaches that consider the mode of vaccine action to be either "all-or-nothing" or "leaky". Our view based on this analysis is that individual variation in correlates of protection is an important consideration that may be crucial to designing and implementing models for estimating population-level impacts of vaccination programs.

The health impact of long COVID during the 2021-2022 Omicron wave in Australia: a quantitative burden of disease study.

BACKGROUND: Long COVID symptoms occur for a proportion of acute COVID-19 survivors, with reduced risk among the vaccinated and for Omicron compared with Delta variant infections. The health loss attributed to pre-Omicron long COVID has previously been estimated using only a few major symptoms. METHODS: The years lived with disability (YLDs) due to long COVID in Australia during the 2021-22 Omicron BA.1/BA.2 wave were calculated using inputs from previously published case-control, cross-sectional or cohort studies examining the prevalence and duration of individual long COVID symptoms. This estimated health loss was compared with acute SARS-CoV-2 infection YLDs and years of life lost (YLLs) from SARS-CoV-2. The sum of these three components equals COVID-19 disability-adjusted life years (DALYs); this was compared with DALYs from other diseases. RESULTS: A total of 5200 [95% uncertainty interval (UI) 2200-8300] YLDs were attributable to long COVID and 1800 (95% UI 1100-2600) to acute SARS-CoV-2 infection, suggesting long COVID caused 74% of the overall YLDs from SARS-CoV-2 infections in the BA.1/BA.2 wave. Total DALYs attributable to SARS-CoV-2 were 50 900 (95% UI 21 000-80 900), 2.4% of expected DALYs for all diseases in the same period. CONCLUSION: This study provides a comprehensive approach to estimating the morbidity due to long COVID. Improved data on long COVID symptoms will improve the accuracy of these estimates. As data accumulate on SARS-CoV-2 infection sequelae (e.g. increased cardiovascular disease rates), total health loss is likely to be higher than estimated in this study. Nevertheless, this study demonstrates that long COVID requires consideration in pandemic policy planning, given it is responsible for the majority of direct SARS-CoV-2 morbidity, including during an Omicron wave in a highly vaccinated population.

Epidemiologic and economic modelling of optimal COVID-19 policy: public health and social measures, masks and vaccines in Victoria, Australia.

Background: Identifying optimal COVID-19 policies is challenging. For Victoria, Australia (6.6 million people), we evaluated 104 policy packages (two levels of stringency of public health and social measures [PHSMs], by two levels each of mask-wearing and respirator provision during large outbreaks, by 13 vaccination schedules) for nine future SARS-CoV-2 variant scenarios. Methods: We used an agent-based model to estimate morbidity, mortality, and costs over 12 months from October 2022 for each scenario. The 104 policies (each averaged over the nine future variant scenarios) were ranked based on four evenly weighted criteria: cost-effectiveness from (a) health system only and (b) health system plus GDP perspectives, (c) deaths and (d) days exceeding hospital occupancy thresholds. Findings: More compared to less stringent PHSMs reduced cumulative infections, hospitalisations and deaths but also increased time in stage ≥3 PHSMs. Any further vaccination from October 2022 decreased hospitalisations and deaths by 12% and 27% respectively compared to no further vaccination and was usually a cost-saving intervention from a health expenditure plus GDP perspective. High versus low vaccine coverage decreased deaths by 15% and reduced time in stage ≥3 PHSMs by 20%. The modelled mask policies had modest impacts on morbidity, mortality, and health system pressure. The highest-ranking policy combination was more stringent PHSMs, two further vaccine doses (an Omicron-targeted vaccine followed by a multivalent vaccine) for ≥30-year-olds with high uptake, and promotion of increased mask wearing (but not Government provision of respirators). Interpretation: Ongoing vaccination and PHSMs continue to be key components of the COVID-19 pandemic response. Integrated epidemiologic and economic modelling, as exemplified in this paper, can be rapidly updated and used in pandemic decision making. Funding: Anonymous donation, University of Melbourne funding.

Intrauterine HIV exposure is associated with linear growth restriction among Ethiopian children in the first 18 months of life.

OBJECTIVE: The role of HIV exposure in determining growth among HIV-uninfected children is debated. We determined whether intrauterine HIV exposure influences linear growth in a cohort of Ethiopian children followed up to 18 months of age in public health facilities in Adama city, Ethiopia. METHODS: Participants were offspring of pregnant women enrolled in a prospective cohort study that included screening for HIV infection during antenatal care. Growth patterns of HIV-exposed and uninfected (HEU) and HIV-unexposed (HU) children were compared up to 18 months of age, with length-for-age z-score (LAZ) and proportion with stunting as primary outcomes. Multivariable linear and logistic regression models were constructed to investigate the associations between HIV exposure and linear growth, controlling for socio-demographic factors and breastfeeding status. RESULTS: Of 1705 included infants (164 HEU), 1276 remained in follow-up at 18 months. Among HIV-positive mothers, 132 (80.5%) were receiving antiretroviral therapy at enrolment. At the 18-month visit, mean LAZ was -1.08 among HEU children and -0.74 among HU children (p = 0.052). Proportions of HEU and HU children with stunting at the 18-month visit were 27.8% and 18.7%, respectively (p = 0.010). In multivariable models, HIV exposure was associated with lower LAZ at all follow-up visits, and with stunting at the 18-month visit (adjusted odds ratio 2.29, 95% confidence interval 1.40-3.71). HIV exposure was not associated with weight-related growth outcomes. CONCLUSIONS: HEU children in Ethiopia had inferior linear growth compared with HU children, implying that intrauterine HIV exposure impacts early childhood growth in this setting.

A log-odds system for waning and boosting of COVID-19 vaccine effectiveness.

Immunity to SARS-CoV-2 following vaccination wanes over time in a non-linear fashion, making modelling of likely population impacts of COVID-19 policy options challenging. We observed that it was possible to mathematize non-linear waning of vaccine effectiveness (VE) on the percentage scale as linear waning on the log-odds scale, and developed a random effects logistic regression equation based on UK Health Security Agency data to model VE against Omicron following two and three doses of a COVID-19 vaccine. VE on the odds scale reduced by 47% per month for symptomatic infection after two vaccine doses, lessening to 35% per month for hospitalisation. Waning on the odds scale after triple dose vaccines was 35% per month for symptomatic disease and 19% for hospitalisation. This log-odds system for estimating waning and boosting of COVID-19 VE provides a simple solution that may be used to parametrize SARS-CoV-2 immunity over time parsimoniously in epidemiological models.

Men who have sex with men diagnosed with a sexually transmitted infection are significantly more likely to engage in sexualised drug use.

The sexualised use of recreational drugs (Mephedrone, GBL/GHB, Crystal Meth) generally known as 'chemsex' in men who have sex with men (MSM) is thought to be associated with sexually transmitted infection (STI) acquisition; however there is little data showing a direct relationship. We reviewed 130 randomly selected cases of MSM with an STI attending our STI service and 130 controls (MSM attending the STI service who did not have an STI) between 5 May 2015 and 2 November 2015. Reported condomless anal sex was significantly higher in cases 90/121 (74%) compared with controls 65/122 (53%); ( χ2 = 11.71, p < 0.005, OR 2.54). Recreational drug use in the cases 38/122 (31%) was significantly greater than in controls 20/125 (16%); ( χ2 = 7.88, p < 0.005, OR 2.37). This demonstrates a link between STI acquisition and recreational drug use in MSM. Harm reduction initiatives identifying and addressing party drug use can help to improve the sexual health of MSM, including reducing risk-taking behaviours.

The pro-apoptotic BH3-only protein Bid is dispensable for development of insulitis and diabetes in the non-obese diabetic mouse.

Type 1 diabetes is caused by death of insulin-producing pancreatic beta cells. Beta-cell apoptosis induced by FasL may be important in type 1 diabetes in humans and in the non-obese diabetic (NOD) mouse model. Deficiency of the pro-apoptotic BH3-only molecule Bid protects beta cells from FasL-induced apoptosis in vitro. We aimed to test the requirement for Bid, and the significance of Bid-dependent FasL-induced beta-cell apoptosis in type 1 diabetes. We backcrossed Bid-deficient mice, produced by homologous recombination and thus without transgene overexpression, onto a NOD genetic background. Genome-wide single nucleotide polymorphism analysis demonstrated that diabetes-related genetic regions were NOD genotype. Transferred beta cell antigen-specific CD8+ T cells proliferated normally in the pancreatic lymph nodes of Bid-deficient mice. Moreover, Bid-deficient NOD mice developed type 1 diabetes and insulitis similarly to wild-type NOD mice. Our data indicate that beta-cell apoptosis in type 1 diabetes can proceed without Fas-induced killing mediated by the BH3-only protein Bid.