Severity of COVID-19 among Residents in Aged Care Facilities in Victoria, Australia: A Retrospective Cohort Study Comparing the Delta and Omicron Epidemic Periods.

OBJECTIVES: During the COVID-19 pandemic, no country with widespread community transmission has avoided outbreaks or deaths in residential aged care facilities (RACFs). As RACF residents are at high risk of morbidity and mortality from COVID-19, understanding disease severity risk factors is imperative. DESIGN: This retrospective cohort study aimed to compare COVID-19 disease severity (hospitalization and deaths) and associated risk factors among RACF residents in Victoria, Australia, across Delta and Omicron epidemic periods. SETTINGS AND PARTICIPANTS: Resident case hospitalization risk (HR) and case fatality risk (CFR) were assessed using Victorian RACFs COVID-19 outbreaks data across 2 epidemic periods; Delta, 994 resident cases linked to 86 outbreaks; and Omicron, 1882 resident cases linked to 209 outbreaks. METHODS: Adjusting for outbreak-level clustering, age, sex, up-to-date vaccination status, and time since last vaccination, the odds of hospitalization and death were compared using mixed effects logistic regression. RESULTS: The HR and CFR was lower during the Omicron period compared with the Delta period [HR 8.2% vs 24.6%, odds ratio (OR) 0.17, 95% CI 0.11-0.26, and CFR: 11.4% vs 18.7%, OR 0.40, 95% CI 0.28-0.56]. During both periods, males had higher odds of hospitalization and odds of death; being up to date with vaccination reduced odds of hospitalization by 40% (excluding nonemergency patient transfers) and odds of death by 43%; and for each month since last vaccination, odds of hospitalization increased by 9% and odds of death by 16%. CONCLUSIONS AND IMPLICATIONS: This study provides empirical evidence of lower COVID-19 severity among RACF residents in the Omicron period and highlights the importance of up-to-date and timely vaccination to reduce disease severity in this cohort.

Identification and characterization of the functional toxboxes in the Vibrio cholerae cholera toxin promoter.

Following the consumption of contaminated food or water by a human host, the Vibrio cholerae bacterium produces virulence factors, including cholera toxin (CT), which directly causes voluminous diarrhea, producing cholera. A complex regulatory network controls virulence gene expression and responds to various environmental signals and transcription factors. Ultimately, ToxT, a member of the AraC/XylS transcription regulator family, is responsible for activating the transcription of the virulence genes. ToxT-regulated promoters all contain one or more copies of the toxbox, a 13-bp DNA sequence which ToxT recognizes. Nucleotides 2 through 7 of the toxbox sequence are well conserved and contain an invariant tract of four consecutive T nucleotides, whereas the remainder of the toxbox sequence is not highly conserved other than being A/T rich. The binding of ToxT to toxboxes is required to activate the transcription of virulence genes, and toxboxes in several virulence gene promoters have been characterized. However, the toxboxes required for the activation of transcription from the cholera toxin promoter PctxAB have not been identified. PctxAB contains a series of heptad repeats (GATTTTT), each of which matches the 5' end of the toxbox consensus sequence and is a potential binding site for ToxT. Using site-directed mutagenesis and high-resolution copper-phenanthroline footprinting, we have identified the functional toxboxes required for the ToxT activation of PctxAB. Our findings suggest that ToxT binds to only two toxboxes within PctxAB, despite the presence of several other potential ToxT binding sites within the promoter. Both toxboxes are essential for DNA binding and the full activation of ctxAB transcription.

A Novel Approach to Managing a COVID-19 Outbreak at a Farm in Outer Regional Victoria, Australia.

The coronavirus disease (COVID-19) has been established as a major occupational health and safety issue that compounds pre-existing socioeconomic inequalities such as access to basic health services. This is exacerbated in migrant farmworkers who are an essential workforce in maintaining food supply across the country. An outbreak occurred in a remote part of Victoria with limited access to healthcare resources. Existing relationships allowed the Loddon Mallee Public Health Unit to quickly engage farm management and local pathology services and provide cultural and language support. After contact-tracing and comprehensive clinical review, rather than isolate positive cases, those who were asymptomatic and willing to work continued to do so whilst negative workers were in quarantine. Outbreak management and public health actions were quickly implemented even when the nationwide state-testing and contact-tracing systems were experiencing significant strain due to the rapid escalation in case numbers. Despite a large outbreak (68/74 workers), the management of the outbreak allowed asymptomatic cases to perform their work so farm productivity remained uninterrupted. Cases' health status was closely monitored, with no adverse outcomes in a high-risk population. COVID-19 negative workers safely quarantined away from positive cases until the closure of the outbreak.