Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells via cell-cell signaling.

Mitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E (CoV-229E), and results in increased intracellular levels of MAVS. In this study, we explored the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (e.g. via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 min and in unexposed controls at 30-40% and at 100% confluency, and in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. MAVS was also assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. Our results showed that UVA increases the expression of MAVS protein. Further, cells in a confluent monolayer exposed to UVA conferred an elevation in MAVS in cells adjacent to the exposed section, and also in cells in the most distant sections which were not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to confluent cells not exposed to UVA, likely via cell-cell signaling.

Endotracheal Application of Ultraviolet A Light in Critically Ill Patients with Severe Acute Respiratory Syndrome Coronavirus 2: A First-in-Human Study.

INTRODUCTION: Our previous preclinical experiments show that under specific and monitored conditions, ultraviolet A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. The goal of this study was to evaluate the safety and effects of narrow-band UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Newly intubated, mechanically ventilated adults with SARS-CoV-2 infection and an endotracheal tube size of at least 7.50 mm were eligible for inclusion in the study. Subjects were treated with UVA for 20 min daily for 5 days and followed for 30 days. RESULTS: Five subjects were enrolled (mean age 56.60 years, three male). At baseline, all subjects scored 9/10 on the World Health Organization (WHO) clinical severity scale (10 = death), with predicted mortality ranging from 21% to 95%. Average endotracheal viral load significantly reduced from baseline to day 5 (- 2.41 log; range - 1.16 to - 4.54; Friedman p = 0.002) and day 6 (- 3.20; range - 1.20 to - 6.77; Friedman p < 0.001). There were no treatment-emergent adverse events, with no changes in oxygenation or hemodynamics during the 20-min treatments. One subject died 17 days after enrollment due to intracranial hemorrhagic complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, clinical improvement correlated with reduction of viral load (Spearman's rho = 1, p < 0.001). CONCLUSIONS: In this first-in-human study, endotracheal narrow-band UVA therapy, under specific and monitored settings, appears to be safe and associated with a reduction in respiratory SARS-CoV-2 viral burden over the treatment period. UVA therapy may provide a novel approach in the fight against COVID-19. CLINICAL TRIAL NUMBER: NCT04572399.