Endotracheal Application of Ultraviolet A Light in Critically Ill Patients with Severe Acute Respiratory Syndrome Coronavirus 2: A First-in-Human Study
Ali Rezaie, Gil Y Melmed, Gabriela Leite, Ruchi Mathur, Will Takakura, Isabel Pedraza, Michael Lewis, Rekha Murthy, George Chaux, Mark Pimentel
Advances in Therapy, doi:10.1007/s12325-021-01830-7
preclinical experiments show that under specific and monitored conditions, ultraviolet A (UVA) exposure reduces certain bacteria, fungi, and viruses including
Author Contributions. Study concept and design: AR, GYM, RM, MP, GC, IP, ML, RM.Acquisition of data: AR, GYM, WT, GL, GC, IP.Analysis and interpretation of data: AR, GYM, GL, RM, MP, WT, GC.Drafting of the manuscript: AR, GL, GYM, RM, MP.Critical revision of the manuscript for important intellectual content: all authors Compliance with Ethics Guidelines. The trial protocol (ClinicalTrials.gov number NCT04572399) was approved by the institutional review board of Cedars-Sinai, Los Angeles, California, USA, and was overseen by an independent data and safety monitoring board (DSMB). Subjects' legally authorized representatives provided written informed consent. The study was conducted according to the guidelines of the Declaration of Helsinki. Data Availability. All data generated or analyzed during this study are included in this published article or in the supplementary information files. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in..
References
Alhazzani, Evans, Alshamsi, Surviving sepsis campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update, Crit Care Med,
doi:10.1097/CCM.0000000000004899
Datta, Talwar, Lee, A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: illness beyond acute infection and public health implications, JAMA,
doi:10.1001/jama.2020.22717
Fletcher-Sandersjoo, Bartek, Jr, Predictors of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation: an observational cohort study, J Intensive Care,
doi:10.1186/s40560-017-0223-2
Fu, Wang, Zheng, SARS-CoV-2 membrane glycoprotein M antagonizes the MAVSmediated innate antiviral response, Cell Mol Immunol,
doi:10.1038/s41423-020-00571-x
Hamet, Pavon, Dalle, Candida spp. airway colonization could promote antibiotic-resistant bacteria selection in patients with suspected ventilator-associated pneumonia, Intensive Care Med,
doi:10.1007/s00134-012-2584-2
Leite, Rezaie, Mathur, Barlow, Melmed et al., Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells even at a distance from the light source, bioRxiv,
doi:10.1101/2021.05.11.443549
Luyt, Sahnoun, Gautier, Ventilatorassociated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study, Ann Intensive Care,
doi:10.1186/s13613-020-00775-4
Metnitz, Moreno, Almeida, SAPS 3-From evaluation of the patient to evaluation of the intensive care unit. Part 1: objectives, methods and cohort description, Intensive Care Med,
doi:10.1007/s00134-005-2762-6
Mohanty, Tiwari-Pandey, Pandey, Mitochondria: the indispensable players in innate immunity and guardians of the inflammatory response, J Cell Commun Signal,
doi:10.1007/s12079-019-00507-9
Moreno, Metnitz, Almeida, SAPS 3-From evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission, Intensive Care Med,
doi:10.1007/s00134-005-2763-5
Sklar, Sy, Lequier, Kanji, Anticoagulation practices during venovenous extracorporeal membrane oxygenation for respiratory failure. A systematic review, Ann Am Thorac Soc,
doi:10.1513/AnnalsATS.201605-364SR
Sungnak, Huang, Becavin, SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Nat Med,
doi:10.1038/s41591-020-0868-6
Team, Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States, Nat Med,
doi:10.1038/s41591-020-0877-5
Vahidy, Drews, Masud, Characteristics and outcomes of COVID-19 patients during initial peak and resurgence in the houston metropolitan area, JAMA,
doi:10.1001/jama.2020.15301
Vieyra-Garcia, Wolf, A deep dive into UVbased phototherapy: mechanisms of action and emerging molecular targets in inflammation and cancer, Pharmacol Ther,
doi:10.1016/j.pharmthera.2020.107784
Vincent, Moreno, Takala, The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine, Intensive Care Med,
doi:10.1007/BF01709751
Winter, Using the Student's t-test with extremely small sample sizes, Pract Assess Res Eval
Wu, Shi, Pan, SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO, Cell Rep,
doi:10.1016/j.celrep.2021.108761
Zheng, Yu, Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study, BMJ,
doi:10.1136/bmj.m1443
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