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.

Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps.

Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophils being rapidly recruited and deploying NETs around skin-penetrating larvae. Neutrophils depletion or NET inhibition altered larvae behavior and enhanced the number of adult worms following murine infection. Nevertheless, larvae were able to mitigate the effect of NETs by secreting a deoxyribonuclease (Nb-DNase II) to degrade the DNA backbone. Critically, neutrophils were able to kill larvae in vitro, which was enhanced by neutralizing Nb-DNase II. Homologs of Nb-DNase II are present in other nematodes, including the human hookworm, Necator americanus, which also evaded NETs in vitro. These findings highlight the importance of neutrophils in hookworm infection and a potential conserved mechanism of immune evasion.