Visible blue light inactivates SARS-CoV-2 variants and inhibits Delta replication in differentiated human airway epithelia.

The emergence of SARS-CoV-2 variants that evade host immune responses has prolonged the COVID-19 pandemic. Thus, the development of an efficacious, variant-agnostic therapeutic for the treatment of early SARS-CoV-2 infection would help reduce global health and economic burdens. Visible light therapy has the potential to fill these gaps. In this study, visible blue light centered around 425 nm efficiently inactivated SARS-CoV-2 variants in cell-free suspensions and in a translationally relevant well-differentiated tissue model of the human large airway. Specifically, 425 nm light inactivated cell-free SARS-CoV-2 variants Alpha, Beta, Delta, Gamma, Lambda, and Omicron by up to 99.99% in a dose-dependent manner, while the monoclonal antibody bamlanivimab did not neutralize the Beta, Delta, and Gamma variants. Further, we observed that 425 nm light reduced virus binding to host ACE-2 receptor and limited viral entry to host cells in vitro . Further, the twice daily administration of 32 J/cm 2 of 425 nm light for three days reduced infectious SARS-CoV-2 Beta and Delta variants by >99.99% in human airway models when dosing began during the early stages of infection. In more established infections, logarithmic reductions of infectious Beta and Delta titers were observed using the same dosing regimen. Finally, we demonstrated that the 425 nm dosing regimen was well-tolerated by the large airway tissue model. Our results indicate that blue light therapy has the potential to lead to a well-tolerated and variant-agnostic countermeasure against COVID-19.

Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue.

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).

Five-year-olds do not show ambiguity aversion in a risk and ambiguity task with physical objects.

Ambiguity aversion arises when a decision maker prefers risky gambles with known probabilities over equivalent ambiguous gambles with unknown probabilities. This phenomenon has been consistently observed in adults across a large body of empirical work. Evaluating ambiguity aversion in young children, however, has posed methodological challenges because probabilistic representations appropriate for adults might not be understood by young children. Here, we established a novel method for representing risk and ambiguity with physical objects that overcomes previous methodological limitations and allows us to measure ambiguity aversion in young children. We found that individual 5-year-olds exhibited consistent choice preferences and, as a group, exhibited no ambiguity aversion in a task that evokes ambiguity aversion in adults. Across individuals, 5-year-olds exhibited greater variance in ambiguity preferences compared with adults tested under similar conditions. This suggests that ambiguity aversion is absent during early childhood and emerges over the course of development.

Non-symbolic approximate arithmetic training improves math performance in preschoolers.

Math proficiency at early school age is an important predictor of later academic achievement. Thus, an important goal for society should be to improve math readiness in preschool-age children, especially in low-income children who typically arrive in kindergarten with less mathematical competency than their higher income peers. The majority of existing research-based math intervention programs target symbolic verbal number concepts in young children. However, very little attention has been paid to the preverbal intuitive ability to approximately represent numerical quantity, which is hypothesized to be an important foundation for full-fledged mathematical thinking. Here, we tested the hypothesis that repeated engagement of non-symbolic approximate addition and subtraction of large arrays of items results in improved math skills in very young children, an idea that stems from our previous studies in adults. In the current study, 3- to 5-year-olds showed selective improvements in math skills after multiple days of playing a tablet-based non-symbolic approximate arithmetic game compared with children who played a memory game. These findings, collectively with our previous reports, suggest that mental manipulation of approximate numerosities provides an important tool for improving math readiness, even in preschoolers who have yet to master the meaning of number words.