Far‐UVC Light at 222 nm is Showing Significant Potential to Safely and Efficiently Inactivate Airborne Pathogens in Occupied Indoor Locations

Far UVC light (UVC wavelengths below 235 nm) is a comparatively new modality with significant potential to safely and very efficiently inactivate airborne pathogens in occupied indoor locations. There are now significant accumulations of evidence both in terms of the safety of far‐UVC for direct exposure of occupied indoor locations, and in terms of its efficacy to markedly reduce the levels of active airborne pathogens This article reviews both the safety of far‐UVC, which has a clear mechanistic underpinning, and its efficacy, both in the laboratory and in full‐sized rooms. Highlighted is the paper by Ma et al. in this issue of Photochemistry and Photobiology which addresses the efficacy of far‐UVC light (in this case at 222 nm) against a broad spectrum of common pathogens including SARS‐CoV‐2 and influenza viruses. From their data, and based on our understanding of the largely random nature of UVC‐induced damage within the genome, far UVC would be expected to be effective against the next pandemic virus, if and when it emerges.


COMMENTARY
A potentially important paper from Ma et al. in this issue shows that far-UVC light (defined as wavelengths less than 235 nm, in this case 222 nm) is extremely efficient at inactivating a number of common pathogens. In summary very low doses of 222 nm far-UVC were very efficient at inactivating all 12 of the pathogens studied, including five pathogenic bacteria, two surrogate bacteria, three pathogenic viruses and two surrogate viruses. Of particular interest for the potential widespread application of far-UVC for inactivating airborne viruses is that the three pathogenic viruses studied (SARS-CoV-2 [delta variant], seasonal human coronavirus , and influenza A [H1N1]) all had similar (and high) low-dose inactivation sensitivities for 222 nm far-UVC.
The context here is that conventional germicidal UVC, typical at higher wavelengths around 254 nm, has been successfully used for many decades to inactivate pathogens in air and on surfaces-and indeed a successful study was reported in the 1940's using conventional 254 nm germicidal UVC to limit airborne measles transmission in schools during an epidemic (1). However conventional germicidal UVC (≥254 nm) cannot practically be used to directly expose indoor locations in the lower part of an occupied room-that is, where people are located-because of potential safety issues, both to the skin and the eyes. By contrast, and as illustrated in Fig. 1 (2), far-UVC wavelengths (e.g. 222 nm) are far less penetrating in biological materials, being highly attenuated both by the stratum corneum (dead cell layer on the outer surface of the skin), and by the tear layer at the outer surface of the eye. This difference in penetration relative to conventional ≥254 nm UVC is due to increased protein absorption at lower UVC wavelengths, resulting in less penetration through biological materials (3,4). By contrast, because viruses and bacteria are physically much smaller than these human tissue dimensions, far-UVC light can efficiently penetrate and thus inactivate these pathogens. Based on these considerations, far-UVC has been suggested (5,6), and is now starting to be deployed (7), for direct overhead exposure in occupied indoor locations with the goal of reducing airborne pathogen concentrations in the vicinity of the room occupants. There are essentially only two questions: Does it work? Is it safe? Over the past few years a significant body of evidence has emerged suggesting that the answer to both these questions is "yes", as we briefly discuss: Starting with the question of far-UVC efficacy, the highlighted paper by Ma et al. suggested that far-UVC will be useful against a broad spectrum of common airborne pathogens including SARS-CoV-2 and influenza, and so it is tempting to suggest that it is likely to be as effective against the next pandemic virus, if and when it emerges. This is generally not so surprising as UVC inactivates pathogens primarily through genomic damage located randomly throughout the genome (8), so inactivation rates are expected to show limited dependence on the detailed structure of different pathogens. And indeed the first laboratory studies of far-UVC inactivation of aerosolized viruses showed quite similar results for H1N1 influenza and two seasonal human coronaviruses (6,9).
Of course, these early studies of far-UVC efficacy studies were laboratory based, and the obvious question is whether their conclusions can be scaled up to room-sized dimensions. The answer at this time appears to be "yes," with the recent publication of a far-UVC air disinfection study in a full-sized room containing a continuous source of airborne pathogens: the results (10) (and see Fig. 2) show that levels of far-UVC light based on current US regulatory (American Conference of Governmental Industrial Hygienists, ACGIH) recommendations can result in as much as 180 equivalent air changes per hour (eACH), whilst the corresponding results with the lower far-UVC exposures consistent with the international regulatory recommendations (International Commission on Non-Ionizing Radiation Protection, ICNIRP) provided about 30 eACH (more about these regulatory recommendations below). Both of these eACH numbers are significantly larger than are achievable with most other air-cleaning technologies (11). The bottom line is that, particular for a highly transmissible viruses such as the SARS-CoV-2 Omicron variant, the higher the eACH that can be achieved, the more protection the room occupants will receive from disease transmission (5,11), so in-room measured values from far-UVC of 30 and 180 eACH are very encouraging.
A second far-UVC study in a full-sized room has recently been published (12), which shows encouraging results consistent with the first (10) full-sized room study.
The second aspect of far-UVC is, of course safety. The biophysical rationale for far-UVC safety was outlined above (and see Fig. 1) with the stratum corneum (13) and the tear-film layer (14) respectively acting as protective dead-cell layers for the epidermis and the ocular cornea. These consideration have been validated both with modeling studies (15) and direct measurements of DNA damage throughout the epidermis and the cornea after far-UVC exposure (16,17).
One example is shown in Fig. 3 which shows measured damage in the epidermis of a human skin model as a function of UVC wavelength (16); unlike conventional germicidal UVC wavelengths, far-UVC did not produce significant DNA damage, but as the UVC wavelength was increased, significant epidermal damage was observed.
The studies discussed above largely relate to short term exposures. Of relevance therefore is a far-UVC safety study (18) of hairless mice exposed continuously for 65 weeks to far-UVC light at both current and past ACGIH TLV levels (see below). The conclusion of this study was that "no evidence for increased skin cancer, abnormal skin growths or incidental skin pathology findings was observed in the far-UVC-exposed mice." Compared with skin studies, there have been comparatively fewer studies of ocular safety after far-UVC exposure. In part, this may be because in the expected geometry of overhead far-UVC lighting, the eye dose to a room occupant is typically only a few percent of the maximum skin dose (19). Extensive studies in rat eyes by Kaidzu et al. (17) concluded that the minimum far-UVC dose to induce corneal damage was far larger than the recommended regulatory limits (see below). A first in-situ study of human eye safety after long term far-UVC exposure was recently published (20), showing no adverse effects after 12-month exposures using multiple endpoints based on slit lamp examinations.
One important caveat to the safety studies described above: The current technology for producing far-UVC light is with excimer lamps respectively producing emissions at 207 nm (KrBr* lamp) or 222 nm (KrCl* lamp). While these lamps produce most of their output at their nominal emission wavelengths, they do emit a small  . Measured DNA damage in the epidermis of a human skin model exposed to 100 mJ cm À2 at different UVC wavelengths. Far-UVC (wavelengths ≤235 nm) did not produce significant DNA damage (in this case cyclobutane pyrimidine dimer [CPD] damage) in the epidermis. By contrast the same exposures of conventional germicidal UVC (≥240 nm) did produce significant measured DNA damage (from Ref. (16)). percentage of the spectral irradiance (~5%) at higher wavelengths, where the rationale for far-UVC safety no longer holds (see for example Fig. 3). There is clear evidence (21,22) that these higherwavelength trace emissions from excimer lamps do compromise the safety of far-UVC, and thus it is important that optical filters are always used to attenuate these higher wavelength photons. In practice almost all far-UVC vendors do use appropriate optical filters.
Beyond the basic biophysics and extensive experimental studies, a third consideration in terms of far-UVC safety relates to the current regulatory framework for far-UVC. There are two organizations, one for the United States (American Conference of Governmental Industrial Hygienists, ACGIH) and one covering other countries (International Commission on Non-Ionizing Radiation Protection, ICNIRP) that recommended daily exposure guidelines for UV light. Between 1988 and 2022 both organizations had the same recommended guidelines for far-UVC, specifically 23 mJ cm À2 /8-h day. Since January 2022 the recommended daily exposure guidelines as set by ACGIH in the far-UVC range were increased significantly; specifically, based on their updated analysis (23,24) of available published data, ACGIH increased their recommended daily exposure guidelines at 222 nm by seven-fold for the eye and by 20-fold for the skin (25).

CONCLUSIONS
• The evidence for far-UVC efficacy is strong, with clear evidence that far-UVC can produce Equivalent Air Change rates that are higher than for any other practical indoor air-cleaning approach. The paper by Ma et al. in the current issue provides good evidence that far-UVC will be effective against multiple common pathogens. • The evidence for far-UVC safety after prolonged far-UVC exposures is also strong, assuming that the (1) filtered far-UVC lamps are used, and (2) daily exposures are kept within current regulatory guidelines. The overarching reason to characterize the safety evidence as "strong" is that it comes from three different avenues: First, the basic biophysics of the penetration of far-UVC light into biological material; second, the extensive peer-reviewed published safety data when using filtered far-UVC light, and finally the recent decision of the ACGIH, based on the available experimental evidence, to significantly increase their recommended daily limits for far-UVC light.