Author Correction: Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently kills bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently kills airborne aerosolized viruses, a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.


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Airborne-mediated microbial diseases represent one of the major challenges to worldwide public 26 health 1 . Common examples are influenza 2 , appearing in seasonal 3 and pandemic 4 forms, and bacterially-27 based airborne-mediated diseases such as tuberculosis 5 , increasingly emerging in multi-drug resistant 28 form.

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A direct approach to prevent the transmission of airborne-mediated disease is inactivation of the 30 corresponding airborne pathogens, and in fact the airborne antimicrobial efficacy of ultraviolet (UV) 31 light has long been established 6-8 . Germicidal UV light can also efficiently kill both drug-sensitive and 32 multi-drug-resistant bacteria 9 , as well differing strains of viruses 10 . However, the widespread use of 33 germicidal ultraviolet light in public settings has been very limited because conventional UVC light 34 sources are a human health hazard, being both carcinogenic and cataractogenic 11,12 . 35 By contrast, we have earlier shown that far-UVC light generated by filtered excimer lamps 36 emitting in the 207 to 222 nm wavelength range, efficiently kills drug-resistant bacteria, without 37 apparent harm to exposed mammalian skin [13][14][15] . The biophysical reason is that, due to its strong

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Virus inactivation. Fig. 1 shows representative fluorescent 40x images of mammalian epithelial cells 50 incubated with airborne viruses that had been exposed in aerosolized form to far-UVC doses (0, 0.8, 1.3 51 or 2.0 mJ/cm 2 ) generated by filtered 222-nm excimer lamps. Blue fluorescence was used to identify the 52 total number of cells in a particular field of view, while green fluorescence indicated the integration of 53 live influenza A (H1N1) viruses into the cells. Results from the zero-dose control studies (Fig. 1 Fig. 2 shows the surviving fraction, as a function of the incident 222-nm far-UVC dose, of 57 exposed H1N1 aerosolized viruses, as measured by the number of focus forming units in incubated 58 epithelial cells relative to unexposed controls. Linear regressions (see below) showed that the survival 59 results followed a classical exponential UV disinfection model with rate constant k=1.8 cm 2 /mJ (95% 60 confidence intervals 1.5-2.1 cm 2 /mJ). The overall model fit was good, with a coefficient of 61 determination, R 2 = 0.95, which suggests that most of the variability in virus survival was explained by 62 the exponential model. The rate constant of 1.8 cm 2 /mJ corresponds to an inactivation cross-section 63 (dose required to kill 95% of the exposed viruses) of D95 = 1.6 mJ/cm 2 (95% confidence intervals 1.4-1.9 64 mJ/cm 2 ).

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We have developed an approach to UV-based sterilization using single-wavelength far-UVC 68 light generated by filtered excilamps, which selectively inactivate microorganisms, but does not produce 69 biological damage to exposed mammalian cells and tissues [13][14][15] . The approach is based on biophysical 70 5 principles in that far-UVC light can traverse and therefore kill bacteria and viruses which are typically 71 micrometer dimensions or smaller, whereas due to its strong absorbance in biological materials, far-72 UVC light cannot penetrate even the outer dead-cell layers of human skin, nor the outer tear layer on the 73 surface of the eye.

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Here we applied this approach to test the efficacy of the 222-nm far-UVC light to kill influenza 75 A virus (H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated 76 aerosol droplets of sizes similar to those generated by human coughing and breathing. Aerosolized 77 viruses flowing through the irradiation chamber were exposed to UVC emitting lamps placed in front of 78 the chamber window.  louvers to prevent direct exposure of potentially occupied room areas 21 . This results in blocking more 97 than 95% of the UV radiation exiting the UVGI fixture, with substantial decrease in effectiveness 22 . By 98 contrast, use of low-level far-UVC fixtures, which are potentially safe for human exposure, could 99 provide the desired antimicrobial benefits without the accompanying human health concerns of 100 conventional germicidal lamp UVGI.

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A key advantage of the UVC based approach, which is in clear contrast to vaccination 102 approaches, is that UVC light is likely to be effective against all airborne microbes. For example, while 103 there will almost certainly be variations in UVC inactivation efficiency as different influenza strains 104 appear, they are unlikely to be large 7,10 . Likewise, as multi-drug-resistant variants of bacteria emerge, 105 their UVC inactivation efficiencies are also unlikely to change greatly 9 .

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Finally it is of course by no means the case that all microbes are harmful, and it is well 107 established that the human microbiome is essential to human health 23 . With the exception of a subset of 108 the skin microbiome, all the human microbiome would be entirely shielded from far-UVC light due to 109 its very short range; in fact even within the skin biome only those biota on the skin surface 24 would be   Additional dosimetry to determine the uniformity of the UV exposure was performed using far-UVC 136 sensitive film as described in our previous work 28, 29 . This film has a high spatial resolution with the 137 ability to resolve features to at least 25 µm, and exhibits a nearly ideal cosine response 30,31 . settings, determined the aerosol particle size distribution. An optimal RH value of 55% resulted in a 168 distribution of aerosol particle sizes similar to the natural distribution from human coughing and 169 breathing, which has been shown to be distributed around approximately 1 µm, with a significant tail of 170 particles less than 1 µm 36-38 .

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After combining the humidity control inputs with the aerosolized virus, input flow was directed 172 through a series of baffles that promoted droplet drying and mixing to produce an even particle 173 distribution 34 . The RH and temperature inside the irradiation chamber were monitored using an Omega 174 RH32 meter (Omega Engineering Inc., Stamford, CT) immediately following the baffles. A Hal 175 Technologies HAL-HPC300 particle sizer (Fontana, CA) was adjoined to the irradiation chamber to 176 allow for sampling of particle sizes throughout operation.    where k is the UV inactivation rate constant or susceptibility factor (cm 2 /mJ). The regression was 250 performed with the intercept term set to zero, which represents the definition of 100% relative survival 251 at zero UV dose. Bootstrap 95% confidence intervals for the parameter k were calculated using R 3.2.3 252 software 41 . The virus inactivation cross section, D95, which is the UV dose that inactivates 95% of the