222 nm far-UVC light markedly reduces the level of infectious airborne virus in an occupied room.

An emerging intervention for control of airborne-mediated pandemics and epidemics is whole-room far-UVC (200-235 nm). Laboratory studies have shown that 222-nm light inactivates airborne pathogens, potentially without harm to exposed occupants. While encouraging results have been reported in benchtop studies and in room-sized bioaerosol chambers, there is a need for quantitative studies of airborne pathogen reduction in occupied rooms. We quantified far-UVC mediated reduction of aerosolized murine norovirus (MNV) in an occupied mouse-cage cleaning room within an animal-care facility. Benchtop studies suggest that MNV is a conservative surrogate for airborne viruses such as influenza and coronavirus. Using four 222-nm fixtures installed in the ceiling, and staying well within current recommended regulatory limits, far-UVC reduced airborne infectious MNV by 99.8% (95% CI: 98.2-99.9%). Similar to previous room-sized bioaerosol chamber studies on far-UVC efficacy, these results suggest that aerosolized virus susceptibility is significantly higher in room-scale tests than in bench-scale laboratory studies. That said, as opposed to controlled laboratory studies, uncertainties in this study related to airflow patterns, virus residence time, and dose to the collected virus introduce uncertainty into the inactivation estimates. This study is the first to directly demonstrate far-UVC anti-microbial efficacy against airborne pathogens in an occupied indoor location.

APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors. We report that driver mutations were shared with spontaneous, ultraviolet (UV) light-induced cutaneous SCC (UV SCC) and head and neck SCC (HNSCC) and did not explain the early presentation or aggressive nature of RDEB SCC. Instead, endogenous mutation processes associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases dominated RDEB SCC. APOBEC mutation signatures were enhanced throughout RDEB SCC tumor evolution, relative to spontaneous UV SCC and HNSCC mutation profiles. Sixty-seven percent of RDEB SCC driver mutations was found to emerge as a result of APOBEC and other endogenous mutational processes previously associated with age, potentially explaining a >1000-fold increased incidence and the early onset of these SCCs. Human papillomavirus-negative basal and mesenchymal subtypes of HNSCC harbored enhanced APOBEC mutational signatures and transcriptomes similar to those of RDEB SCC, suggesting that APOBEC deaminases drive other subtypes of SCC. Collectively, these data establish specific mutagenic mechanisms associated with chronic tissue damage. Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB SCC.