Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium Roseomonas mucosa for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of R. mucosa treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, R. mucosa treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced Staphylococcus aureus burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to R. mucosa treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by R. mucosa persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by R. mucosa, cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of R. mucosa treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.
Our work comprises unique data on the characteristics of SARS-CoV-2 dynamics among staff working at LTCFs in the early months of the SARS-CoV-2 pandemic prior to mandated staff surveillance testing. During this time period, LTCF residents were largely sheltering-in-place.
Long-term care facilities (LTCFs) have been disproportionately impacted by COVID-19 due to their communal nature and high-risk profile of residents. LTCF staff have the ability to introduce SARS-CoV-2 into the facility, where it can spread, causing outbreaks.
SARS-CoV-2 has had a disproportionate impact on non-hospital healthcare settings such as long-term care facilities (LTCFs). The communal nature of these facilities, paired with the high-risk profile of residents, has resulted in thousands of infections and deaths and a high case fatality rate. To detect pre-symptomatic infections and identify infected workers, we performed weekly surveillance testing of staff at two LTCFs which revealed a large outbreak at one of the sites. We collected serum from staff members throughout the study and evaluated it for binding and neutralization to measure seroprevalence, seroconversion, and type and functionality of antibodies. At the site with very few incident infections, we detected that over 40% of the staff had preexisting SARS-CoV-2 neutralizing antibodies, suggesting prior exposure. At the outbreak site, we saw rapid seroconversion following infection. Neutralizing antibody levels were stable for many weeks following infection, suggesting a durable, long-lived response. Receptor-binding domain antibodies and neutralizing antibodies were strongly correlated. The site with high seroprevalence among staff had two unique introductions of SARS-CoV-2 into the facility through seronegative infected staff during the period of study but these did not result in workplace spread or outbreaks. Together our results reveal that high seroprevalence rate among staff can contribute to herd immunity within a workplace and protect against subsequent infection and spread within a facility.
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