Endotracheal application of ultraviolet A light in critically ill severe acute respiratory syndrome coronavirus-2 patients: A first-in-human study

Abstract

Background: Promising 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. We aimed to evaluate the safety and effects of UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with SARS-CoV-2 infection. Methods: Five newly intubated mechanically ventilated adults with SARS-CoV-2 infection, with an endotracheal tube size 7.5mm or greater, were treated with UVA for 20 minutes daily for 5 days, and followed for 30 days. Results: Five subjects were enrolled (mean age 56.6yrs, 3 male). At baseline, all subjects scored 9/10 on the WHO clinical severity scale (10=death) with predicted mortality ranging from 21 to 95%. Average log changes in endotracheal viral load from baseline to day 5 and day 6 were -2.41 (range -1.16 to -4.54; Friedman P=0.002) and -3.20 (range -1.20 to -6.77; Friedman P<0.001), respectively. There were no treatment-emergent adverse events. 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, the slope of viral load reduction during UVA treatment correlated with the slope of improvement in clinical WHO severity score over time (Spearman rho=1, P<0.001). Conclusion: In this first-in-human study, endotracheal UVA therapy under specific and monitored settings, was safe with a significant reduction in respiratory SARS-CoV-2 viral burden over the treatment period.

Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells even at a distance from the light source

“…This increased cell survival suggests that perhaps MAVS is a cell salvage pathway. This is also supported by the first in human study of UVA in intubated critically ill subjects with COVID-19 [7]. Two patients underwent bronchoscopy after 5 days of UVA application.…”

“…Secondary bacterial and fungal infections are also common, with ventilator-associated pneumonia (VAP) occurring in 31% of mechanically ventilated patients [20]. To test the safety and efficacy of UVA light as a potential treatment for SARS-CoV-2, we developed a novel UVA light emitting diode (LED)-based catheter device which can be inserted into an endotracheal tube to deliver UVA light in critically ill COVID-19 subjects [7]. In the first human study of mechanically ventilated COVID-19 subjects, all of whom had World Health Organization (WHO) symptom severity scores of 9 at baseline (10 is death) [21], subjects who were treated with endotracheally-delivered UVA light (treated for 20 minutes daily for 5 days) exhibited an average log 10 decrease in SARS-CoV-2 viral load of 3.2 (p<0.001) by day 6 of therapy in endotracheal aspirates, and these accelerated reductions in viral loads correlated with 30-day improvements in the WHO symptom severity scores [7].…”

“…To test the safety and efficacy of UVA light as a potential treatment for SARS-CoV-2, we developed a novel UVA light emitting diode (LED)-based catheter device which can be inserted into an endotracheal tube to deliver UVA light in critically ill COVID-19 subjects [7]. In the first human study of mechanically ventilated COVID-19 subjects, all of whom had World Health Organization (WHO) symptom severity scores of 9 at baseline (10 is death) [21], subjects who were treated with endotracheally-delivered UVA light (treated for 20 minutes daily for 5 days) exhibited an average log 10 decrease in SARS-CoV-2 viral load of 3.2 (p<0.001) by day 6 of therapy in endotracheal aspirates, and these accelerated reductions in viral loads correlated with 30-day improvements in the WHO symptom severity scores [7]. Moreover, the scale of the improvements, despite the fact that only small portions of the trachea were exposed to UVA light, suggested the possibility that the antiviral effects of UVA light might not be confined to cells directly exposed to UVA, but might also be transmitted to neighboring cells.…”

“…This suggested that UVA may activate MAVS. Further, in a first-in-human clinical trial in ventilated subjects with coronavirus disease 2019 (COVID- 19), a 20-minute endotracheal UVA treatment daily for 5 days resulted in significantly decreased respiratory SARS-CoV-2 viral loads [7]. Interestingly, despite time-.…”

“…This suggested that UVA may activate MAVS. Further, in a first-in-human clinical trial in ventilated subjects with coronavirus disease 2019 (COVID-19), a 20-minute endotracheal UVA treatment daily for 5 days resulted in significantly decreased respiratory SARS-CoV-2 viral loads [7]. Interestingly, despite time-limited localized UVA therapy in this trial, average log 10 changes in endotracheal viral load from baseline to day 6 was −3.2, suggesting a potential antiviral phenomenon beyond immediate localized effects.…”