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

Abstract

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.

Keywords: Endotracheal administration; SARS-CoV-2; Ultraviolet A light; Viral load.

© 2021. The Author(s).

Figures

Fig. 1

Device components. Left panel shows the controller, umbilical (flexible power and air connector between the catheter and the controller), and the air compressor. Right panel shows the catheter enclosed in a plastic sleeve with a port that connects to a double-swivel multi-access port. Chilled air flows inside the catheter during treatment and a heat-detecting thermistor will automatically shut off the controller if catheter temperature rises. The catheter can be safely withdrawn from the endotracheal tube back into the plastic sleeve until reuse in 24 h

Fig. 2

Summary of the timeline and key events for enrolled subjects. Concomitant COVID-19-related medications included: dexamethasone 6 mg daily (all patients), remdesivir 200 mg single dose followed by 100 mg once daily for 10 days (all patients), tocilizumab 400 mg once (patient 2), venous thromboembolism prophylaxis (all patients)

Fig. 3

Individual daily quantification of endotracheal SARS-CoV-2 loads. Subject 2 did not have detectable viral loads at any point in the study

Fig. 4

a Reductions in endotracheal SARS-COV-2 loads from day 0 through day 6 in patients with detectable viral load at baseline. Freidman test is used to analyze differences across daily viral load measurements. b Corresponding viral loads (log) for each subject at baseline, day 5, and day 6. All four subjects who had detectable SARS-CoV-2 loads at baseline showed a decrease in respiratory viral load. Average log changes from baseline to day 5 and day 6 were − 2.41 (relative reduction > 99.00%) and − 3.20 (relative reduction > 99.90%), respectively. c The individual slopes of reduction in SARS-CoV-2 loads during UVA therapy correlated with the slopes of reduction in WHO severity score by day 30

Fig. 5

Bronchoscopy pictures during tracheostomy for patient 3 showing normal trachea without erythema, edema, or friability (left panel). Full thickness penetration of the tracheal wall did not lead to excessive bleeding or hematoma (right panel)