Clinical Application of Ultraviolet C Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 in Contaminated Hospital Environments.

To overcome the ongoing coronavirus disease 2019 (COVID-19) pandemic, transmission routes, such as healthcare worker infection, must be effectively prevented. Ultraviolet C (UVC) (254 nm) has recently been demonstrated to prevent environmental contamination by infected patients; however, studies on its application in contaminated hospital settings are limited. Herein, we explored the clinical application of UVC and determined its optimal dose. Environmental samples (n = 267) collected in 2021 were analyzed by a reverse transcription-polymerase chain reaction and subjected to UVC irradiation for different durations (minutes). We found that washbasins had a high contamination rate (45.5%). SARS-CoV-2 was inactivated after 15 min (estimated dose: 126 mJ/cm2) of UVC irradiation, and the contamination decreased from 41.7% before irradiation to 16.7%, 8.3%, and 0% after 5, 10, and 15 min of irradiation, respectively (p = 0.005). However, SARS-CoV-2 was still detected in washbasins after irradiation for 20 min but not after 30 min (252 mJ/cm2). Thus, 15 min of 254-nm UVC irradiation was effective in cleaning plastic, steel, and wood surfaces in the isolation ward. For silicon items, such as washbasins, 30 min was suggested; however, further studies using hospital environmental samples are needed to confirm the effective UVC inactivation of SARS-CoV-2.

Mapping of UV-C dose and SARS-CoV-2 viral inactivation across N95 respirators during decontamination.

During public health crises like the COVID-19 pandemic, ultraviolet-C (UV-C) decontamination of N95 respirators for emergency reuse has been implemented to mitigate shortages. Pathogen photoinactivation efficacy depends critically on UV-C dose, which is distance- and angle-dependent and thus varies substantially across N95 surfaces within a decontamination system. Due to nonuniform and system-dependent UV-C dose distributions, characterizing UV-C dose and resulting pathogen inactivation with sufficient spatial resolution on-N95 is key to designing and validating UV-C decontamination protocols. However, robust quantification of UV-C dose across N95 facepieces presents challenges, as few UV-C measurement tools have sufficient (1) small, flexible form factor, and (2) angular response. To address this gap, we combine optical modeling and quantitative photochromic indicator (PCI) dosimetry with viral inactivation assays to generate high-resolution maps of "on-N95" UV-C dose and concomitant SARS-CoV-2 viral inactivation across N95 facepieces within a commercial decontamination chamber. Using modeling to rapidly identify on-N95 locations of interest, in-situ measurements report a 17.4 ± 5.0-fold dose difference across N95 facepieces in the chamber, yielding 2.9 ± 0.2-log variation in SARS-CoV-2 inactivation. UV-C dose at several on-N95 locations was lower than the lowest-dose locations on the chamber floor, highlighting the importance of on-N95 dose validation. Overall, we integrate optical simulation with in-situ PCI dosimetry to relate UV-C dose and viral inactivation at specific on-N95 locations, establishing a versatile approach to characterize UV-C photoinactivation of pathogens contaminating complex substrates such as N95s.

The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus.

The germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.

Pulsed blue light inactivates two strains of human coronavirus.

Emerging evidence suggests that blue light has the potential to inactivate viruses. Therefore, we investigated the effect of 405 nm, 410 nm, 425 nm and 450 nm pulsed blue light (PBL) on human alpha coronavirus HCoV-229 E and human beta coronavirus HCoV-OC43, using Qubit fluorometry and RT-LAMP to quantitate the amount of nucleic acid in irradiated and control samples. Like SARS-CoV-2, HCoV-229E and HCoV-OC43 are single stranded RNA viruses transmitted by air and direct contact; they have similar genomic sizes as SARS-CoV-2, and are used as surrogates for SARS-CoV-2. Irradiation was carried out either at 32.4 J cm-2 using 3 mW cm-2 irradiance or at 130 J cm-2 using 12 mW cm-2 irradiance. Results: (1) At each wavelength tested, PBL was antiviral against both coronaviruses. (2) 405 nm light gave the best result, yielding 52.3% (2.37 log10) inactivation against HCoV-OC43 (p < .0001), and a significant 1.46 log 10 (44%) inactivation of HCoV-229E (p < .01). HCoV-OC43, which like SARS-CoV-2 is a beta coronavirus, was more susceptible to PBL irradiation than alpha coronavirus HCoV-229E. The latter finding suggests that PBL is potentially antiviral against multiple coronavirus strains, and that, while its potency may vary from one virus to another, it seems more antiviral against beta coronaviruses, such as HCoV-OC43. (3) Further, the antiviral effect of PBL was better at a higher irradiance than a lower irradiance, and this indicates that with further refinement, a protocol capable of yielding 100% inactivation of viruses is attainable.

UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic.

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm-2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 µWcm-2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.

Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants.

Coronavirus variants are gaining strongholds throughout the globe. Despite early signals that SARS-CoV-2 coronavirus case numbers are easing up in the United States and during the middle of a (not so easy) vaccination roll out, the country has passed a grim landmark of 600,000 deaths. We contend that these numbers would have been much lower if the medical community undertook serious investigations into the potential of low doses of radiation (LDRT) as a mainstream treatment modality for COVID-19 pneumonia. LDRT has been posited to manifest anti-infectious and anti-inflammatory properties at doses of 0.3-1.0 Gy via the activation of the Nrf-2 pathway. Although some researchers are conducting well-designed clinical trials on the potential of LDRT, the deep-rooted, blind, and flawed acceptance of the Linear No-Threshold (LNT) model for ionizing radiation has led to sidelining of this promising therapy and thus unimaginable numbers of deaths in the United States.

Effectiveness of low-dose radiation therapy to improve mortality of COVID-19.

INTRODUCTION: Performing low-dose radiation therapy (LDRT) is a new approach to treat pneumonia resulting from COVID-19 disease. This paper aims to evaluate the effectiveness of LDRT in treating COVID-19 patients. METHODS: Medline was searched for "low-dose" and "radiation therapy" and "COVID-19" and "pneumonia" and "inflammation", to retrieve papers that published on low-dose radiation therapy to improve mortality of COVID-19 patients. Only clinical investigations that included original and case report papers were selected for this paper. RESULTS: The completed clinical trials that have performed LDRT to treat COVID-19 showed that the effectiveness of LDRT in treating COVID-19 was up to 90%. CONCLUSION: The vast majority of primary and secondary outcomes of clinical trial investigations regarding LDRT in treating COVID-19 found that LDRT can be considered a feasible treatment to improve mortality of COVID-19 patients.

Neutralization of the eye and skin irritant benzalkonium chloride using UVC radiation.

PURPOSE: Benzalkonium chloride (BAK) is a widely used disinfectant and preservative which is effective against a wide range of viruses (e.g. SARS-CoV and SARS-CoV-2), bacteria and fungi. However, it is toxic to the eye and skin. This study investigated the neutralization of BAK using ultraviolet C (UVC) radiation as an effort to reduce BAK toxicity potential. METHODS: BAK solutions were irradiated with a germicidal UVC lamp at various doses. Human corneal epithelial cells (HCEC) were then exposed to the UVC-irradiated BAK solutions for 5 minutes. After exposure, the cultures were assessed for metabolic activity using PrestoBlue; for cell viability using confocal microscopy with viability dyes; and for tight junction proteins using immunofluorescence staining for zonula occludens (ZO)-1. RESULTS: UVC radiation reduced BAK toxicity on cell metabolic activity in a dose-dependent manner. When the solution depth of BAK was 1.7 mm, the UVC doses needed to completely neutralize the toxicity of BAK 0.005% and 0.01% were 2.093 J/cm2 and 8.374 J/cm2, respectively. The cultures treated with UVC-neutralized BAK showed similar cell metabolic activity and cell viability to those treated with phosphate buffered saline (PBS) (p = 0.806 ∼ 1.000). The expression of ZO-1 was greatly disturbed by untreated BAK; in contrast, ZO-1 proteins were well maintained after exposure to UVC-neutralized BAK. CONCLUSIONS: Our study demonstrates that the cell toxicity of BAK can be neutralized by UVC radiation, which provides a unique way of detoxifying BAK residues. This finding may be of great value in utilizing the antimicrobial efficacy of BAK (e.g. fighting against SARS-CoV-2) while minimizing its potential hazards to human health and the environment.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

Quantitative UV-C dose validation with photochromic indicators for informed N95 emergency decontamination.

With COVID-19 N95 shortages, frontline medical personnel are forced to reuse this disposable-but sophisticated-multilayer respirator. Widely used to decontaminate nonporous surfaces, UV-C light has demonstrated germicidal efficacy on porous, non-planar N95 respirators when all surfaces receive ≥1.0 J/cm2 dose. Of utmost importance across disciplines, translation of empirical evidence to implementation relies upon UV-C measurements frequently confounded by radiometer complexities. To enable rigorous on-respirator measurements, we introduce a photochromic indicator dose quantification technique for: (1) UV-C treatment design and (2) in-process UV-C dose validation. While addressing outstanding indicator limitations of qualitative readout and insufficient dynamic range, our methodology establishes that color-changing dosimetry can achieve the necessary accuracy (>90%), uncertainty (<10%), and UV-C specificity (>95%) required for UV-C dose measurements. In a measurement infeasible with radiometers, we observe a striking ~20× dose variation over N95s within one decontamination system. Furthermore, we adapt consumer electronics for accessible quantitative readout and use optical attenuators to extend indicator dynamic range >10× to quantify doses relevant for N95 decontamination. By transforming photochromic indicators into quantitative dosimeters, we illuminate critical considerations for both photochromic indicators themselves and UV-C decontamination processes.

Extreme Exposure to Filtered Far-UVC: A Case Study†.

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1500 mJ cm-2 ; whereas, skin yellowing that appeared immediately and resolved within 24 h occurred with a 6000 mJ cm-2 exposure. No erythema was observed at any time point with exposures up to 18 000 mJ cm-2 . These results combined with Monte Carlo Radiative Transfer computer modeling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.

The effect of ultraviolet C radiation against different N95 respirators inoculated with SARS-CoV-2.

OBJECTIVES: There are currently no studies that have examined whether one dosage can be uniformly applied to different respirator types to effectively decontaminate SARS-CoV-2 on N95 filtering facepiece respirators (FFRs). Health care workers have been using this disinfection method during the pandemic. Our objective was to determine the effect of UVC on SARS-CoV-2 inoculated N95 respirators and whether this was respirator material/model type dependent. METHODS: Four different locations (facepiece and strap) on five different N95 FFR models (3M 1860, 8210, 8511, 9211; Moldex 1511) were inoculated with a 10 µL drop of SARS-CoV-2 viral stock (8 × 107 TCID50/mL). The outside-facing and wearer-facing surfaces of the respirators were each irradiated with a dose of 1.5 J/cm2 UVC (254 nm). Viable SARS-CoV-2 was quantified by a median tissue culture infectious dose assay (TCID50). RESULTS: UVC delivered using a dose of 1.5 J/cm2, to each side, was an effective method of decontamination for the facepieces of 3M 1860 and Moldex 1511, and for the straps of 3M 8210 and the Moldex 1511. CONCLUSION: This dose is an appropriate decontamination method to facilitate the reuse of respirators for healthcare personnel when applied to specific models/materials. Also, some straps may require additional disinfection to maximize the safety of frontline workers. Implementation of widespread UVC decontamination methods requires careful consideration of model, material type, design, and fit-testing following irradiation.

Low-Dose Radiation Therapy for COVID-19: Promises and Pitfalls.

The coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 has exacted an enormous toll on healthcare systems worldwide. The cytokine storm that follows pulmonary infection is causally linked to respiratory compromise and mortality in the majority of patients. The sparsity of viable treatment options for this viral infection and the sequelae of pulmonary complications have fueled the quest for new therapeutic considerations. One such option, the long-forgotten idea of using low-dose radiation therapy, has recently found renewed interest in many academic centers. We outline the scientific and logistical rationale for consideration of this option and the mechanistic underpinnings of any potential therapeutic value, particularly as viewed from an immunological perspective. We also discuss the preliminary and/or published results of prospective trials examining low-dose radiation therapy for COVID-19.

Low-dose whole-lung radiation for COVID-19 pneumonia: Planned day 7 interim analysis of a registered clinical trial.

BACKGROUND: Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID-19), especially once they are ventilator-dependent. Respiratory decline in patients with COVID-19 is precipitated by a lung-mediated aberrant immune cytokine storm. Low-dose lung radiation was used to treat pneumonia in the pre-antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID-19. METHODS: A single-institution trial evaluating the safety and efficacy of single-fraction, low-dose whole-lung radiation for patients with COVID-19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating. RESULTS: Of 9 patients screened, 5 were treated with whole-lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64-94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities. CONCLUSIONS: In a pilot trial of 5 oxygen-dependent elderly patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low-dose whole-lung radiation appears to be safe, shows early promise of efficacy, and warrants further study. LAY SUMMARY: Researchers at Emory University report preliminary safety outcomes for patients treated with low-dose lung irradiation for coronavirus disease 2019 (COVID-19) pneumonia. Five residents of nursing or group homes were hospitalized after testing positive for COVID-19. Each had pneumonia visible on a chest x-ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement. A single treatment of low-dose (1.5-Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation therapy. Within 24 hours, 4 patients had rapidly improved breathing, and they recovered to room air at an average of 1.5 days (range, 3-96 hours). Three were discharged at a mean time of 12 days, and 1 was preparing for discharge. Blood tests and repeat imaging confirm that low-dose whole-lung radiation treatment appears safe for COVID-19 pneumonia. Further trials are warranted.

UVC Germicidal Units: Determination of Dose Received and Parameters to be Considered for N95 Respirator Decontamination and Reuse.

The COVID-19 pandemic has resulted in an international shortage of personal protective equipment including N95 filtering facepiece respirators (FFRs), resulting in many institutions using ultraviolet germicidal irradiation (UVGI) technology for N95 FFR decontamination. To ensure proper decontamination, it is crucial to determine the dose received by various parts of the FFR in this process. Recently, our group customized a UVGI unit for N95 decontamination. With experimental and theoretical approach, this manuscript discusses the minimum dose received by various parts of the N95 respirator after one complete decontamination cycle with this UVGI unit. The results demonstrate that all parts of the N95 FFR received at least 1 J cm-2 after one complete decontamination cycle with this unit. As there are a variety of UVGI devices and different types of FFRs, this study provides a model by which UVC dose received by different areas of the FFRs can be accurately assessed to ensure proper decontamination for the safety of healthcare providers.