Rethinking the application of air disinfection in the era of COVID-19.
I first wrote a commentary with a similar title more than 30 years ago during the 1985-1992 resurgence of drug-resistant tuberculosis (TB) in the United States.1 The point was to make clear the quantitative differences between the 3 recommended environmental control interventions at the time: ventilation (fans) and room air cleaners (filters)—both moving air—and upper-room germicidal UV (GUV). Ions (bipolar ions and related catalytic hydrogen peroxide [H2O2] generators) were not prominent interventions at that time. The purpose of this commentary is to update that discussion regarding airborne viral infections (COVID-19 but also seasonal influenza and possible future pandemics) and current technologies, including advances in GUV, air cleaners, and chemical air disinfectants.
The COVID-19 pandemic has stimulated a plethora of environmental solutions—some new, some old, some with a sound scientific rationale and independent evidence of efficacy and safety, others without a solid rationale or independent evidence. Despite their differences, promotions for these various environmental solutions almost always claim 99.9% or greater reduction in pathogens. Some basic principles may help in separating interventions likely to be effective from those less likely to be protective. I will emphasize 2 critical considerations not always evident in the current recommendations or reviews.
Assessing Building Ventilation
To enable comparisons between engineering interventions it is convenient to use 1 of the 2 common ways in which building ventilation is quantified: room air changes per hour (ACH). For this approach, the required ventilation is determined by room volume independent of occupancy, although average room occupancy is assumed. The other common quantifying method is based on occupancy, for example 20 cu ft/min of outside air per occupant in office buildings.3 The total ventilation also assumes average occupancy for the space. The occupancy-based measure of ventilation makes most sense for air contaminants that increase with occupancy, like carbon dioxide (CO2) production and body odor. For airborne infection control, however, there may be just 1 infectious source case in a room of 10 or 20 individuals, and a volume-based ventilation recommendation makes more sense than an occupancy-based one; although, both are important and valid.
One air change in a well-mixed room removes 63% of room air contaminants. The next room air change removes 63% of what remains, and a third 63% of what remains, etc. Each subsequent air change removes a smaller absolute amount of contaminant at greater cost in terms of energy for heating, cooling, and dehumidification, as well as demands on the HVAC system ducts and blowers. The well-known Centers for Disease Control and Prevention recommendation4 of 6 to 12 ACH outside air for respiratory isolation achieves a high percentage reduction in air contamination but does not assume ongoing production of contaminants (ie, the presence of 1 or more infectious source cases in the room). With a highly infectious source like some Omicron cases, and with even 6 to 12 ACH, outside air is beyond the capacity of all but highly advanced ventilation systems in hospital isolation rooms, laboratories, and specialized manufacturing settings.
The requirement of outside air assumes that recirculating contaminants within buildings, although diluting them with air from contaminant-free rooms on the same ventilation circuit, still allows for contaminant buildup and possible room-to-room transmission. Although this has been observed with such infections as measles and TB, I am unaware of convincing reports of room-to-room COVID-19 transmission without in-room contact between individuals, even on ships. SARS-CoV-2 is an envelope virus, especially environmentally fragile compared with other viruses and bacteria. Turbulence, high-velocity impact on surfaces and on fan/blower blades, and high humidity are likely to inactivate SARS-CoV-2.
Despite the lack of evidence that room-to-room transmission is contributing importantly to the transmission of COVID-19, higher-level filtration (MERV 13) has been strongly recommended for HVAC systems in schools and other public places. Although higher-retention filters will remove some respiratory pathogens as well as pollen, dust, etc, they will likely have little impact on SARS-CoV-2 transmission if the virus is not being recirculated to a substantial degree. If greater flow resistance through higher-retention filters reduces HVAC flow rates, filters may increase the risk of in-room transmission. Finally, to an occupant sharing air in a room with an infectious source, there is little comfort knowing that air will be decontaminated only after it leaves the room through the exhaust duct.
Is Ventilation Always Enough?
In 1991, I wrote an article on the theoretical limits of protection provided by building ventilation against airborne infection, using the Wells-Riley equation to analyze an epidemiological investigation of extensive TB transmission in an office building with limited outdoor air ventilation. Whereas 40% of vulnerable occupants (27 of 67) had been infected at a building ventilation rate estimated at 15 cu ft/min outside air per occupant, the analysis showed that at twice the outdoor air ventilation—a very high ventilation rate for an office building—still 20% of occupants likely would be infected. Moreover, to reduce the rate to a still unacceptable 10% (7 individuals), an unrealistic 60 cu ft/min per occupant outdoor air ventilation rate per occupant would be needed (Figure 1). Clearly, ventilation alone, although adequate for removing CO2 and odors, is not adequate for preventing person-to-person airborne transmission of infection when the source is highly infectious or the exposure long, as in this case of TB transmission over a one-month period.
Building ventilation, normally designed for occupant comfort, is rarely adequate for effective air disinfection in the room where transmission is occurring. Comfort-level ventilation requires additional in-room air disinfection. Currently, there are 3 types of technology marketed for in-room air disinfection that I consider safe and effective. They are as follows:
Although there are industry-sponsored chamber studies suggesting that H2O2 and bipolar ions can be effective, these approaches vary greatly from product to product, and there is little peer-reviewed evidence of safety and efficacy under actual application conditions. I will focus on room air cleaners and GUV.
The Cost of Adding Equivalent Air Changes
For any alternative air disinfection technology, when pathogens are reduced by 63%, 1 equivalent air change (EqAC) is said to have occurred (Figure 1).2 This allows comparisons in terms of the cost of providing, for example, 6 ACH though mechanical ventilation vs room air cleaners or GUV. A study conducted in a TB hospital in Vladimir, Russia, in collaboration with the CDC, offered a head-to-head comparison by aerosolizing test bacteria in an unoccupied hospital room and measuring their removal by quantitative air sampling. The results of this unpublished study are shown in Figures 2a and 2b.5
Room air cleaners are a theoretically sound approach to in-room air disinfection, but there are some major limitations. Countless models are marketed using filters, GUV, and even plasma technology claiming to destroy pathogens, not merely retain them in a filter. Whether organisms are inactivated by UV or another technology or retained in a filter is unimportant. All that matters from a room air disinfection perspective is the effective EqACH rate. Each room air cleaner has a clean air delivery rate (CADR) for a specific contaminant—the result of both the flow rate and the per pass removal/inactivation efficiency. Because the per pass inactivation rate for most pathogens usually approaches 100%, the CADR and total flow rate through the device are usually essentially the same. Advertisements often point to the high single-pass efficiency as proof of efficacy, but it is not. Unless the room is very small or the air cleaner is very large (or there are many of them), getting all room air through a fan-driven device at a rate equivalent to even 6 ACH is a challenge because of noise and drafts. Often, room air cleaners contribute just 1 or 2 EqACH. That may not be insignificant if there is little or no other ventilation, but it is hardly highly effective air disinfection. Short-circuiting of just processed air back into the device when intake and outlet are near each other is another reason why the ACH rate may not be an effective ACH rate. In Figures 2a and 2b, 3 different room air cleaners were tested against 2 microbial test aerosols in an actual unoccupied hospital patient room where HVAC system installing and operating costs were known and could be compared with the cost and effectiveness of upper-room GUV and 3 available room air cleaners, including an expensive model with plasma technology used in the Soyuz space capsule. The results show that the least cost per equivalent AC is upper-room UV. Upper-room UV was nearly 10 times more cost-effective than mechanical ventilation in that setting. The GUV fixtures used were inexpensive (less than $200 each) locally made devices to meet Russian performance criteria.
How Well Does GUV Work?
I have referred to several chamber studies in which test organisms are aerosolized and their reduction with GUV or air cleaners quantified. Because they are conducted under controlled conditions, such studies constitute much of the evidence that GUV is effective. But are there any real-world studies or field trials of GUV to show how well it works in reality? There are few because of how difficult such studies are to design and carry out. Perhaps the most impressive was conducted in schools outside of Philadelphia, Pennsylvania, where measles was shown to be prevented in 2 suburban schools by upper-room UV. Similar results were published for an observational study of seasonal influenza in a hospital already equipped with GUV for TB transmission control.6,7
GUV air and surface disinfection technology has advanced greatly since the onset of the COVID-19 pandemic.5 Conventional 254-nm mercury upper-room GUV has been joined by 265-nm to 275-nm LED upper-room sources. Most importantly, new 222-nm krypton chloride far UV lamps are being deployed for whole-room germicidal UV in occupied rooms.8 The efficacy and cost-effectiveness of upper-room GUV is attributable to the treatment of a large swath of upper room all at once as opposed to having to draw air through a box for filtration or internal UV treatment (Figure 3). Rising warm air in most occupied rooms with or without mixing fans allows the entire room air to be rapidly disinfected, equivalent to 10 to 24 ACH in some published reports without noise or risk to room occupants when properly installed.9 Far UV has the advantage of directly treating the air around room occupants, interrupting airborne viruses between the infectious source and other occupants. EqACH of 35 or more have been reported in test chamber studies.10
Safety concerns have been a barrier to the wide application of upper-room GUV, but less so for far UV. Between 254 nm and 275 nm UV must be confined to the upper room to avoid eye exposure above a well-established dose; this is referred to as threshold limit value (TLV).11,12 Accidental overexposure can cause transient but painful eye irritation and skin reddening, which is similar but less severe than more penetrating UV A and B in sunlight. Properly installed upper-room UV should cause no adverse effects of any kind. Workers who are directly exposed to GUV lamps, whether during painting or cleaning of the upper room, may quickly exceed the TLV and experience the equivalent of welder’s flash. Although painful, there are no long-term consequences of acute GUV eye injury. Normal corneal cell turnover replaces damaged cells over the course of a few days. However, 222 nm penetrates human tissues so little that symptomatic eye overexposure is highly unlikely, especially when fixtures are ceiling mounted and shine downward as in the installation pictured in Figure 4.8
Barriers to the wider use of GUV remain and include the primarily accessible technical expertise to plan, install, and maintain GUV systems. This is rapidly changing with greater use.
In summary, I have emphasized that effective air disinfection for highly infectious pathogens like the Omicron variant of COVID-19 needs to be high—more than the 6 to 12 ACH recommended by CDC, and in the room where transmission is occurring as opposed to in the ventilation system. Although room air cleaners can be effective in relatively small rooms, in large-volume spaces it is difficult to achieve high rates of effective EqACH due to noise, drafts, short-circuiting of air, and the flow-limits of the machines themselves. The most effective and cost-effective approach to large volume rooms to achieve the high rates of EqACH needed for the Omicron strain is GUV upper room and, increasingly, 222 nm far UV.10 The role of chemical air disinfection, bipolar ionization, and H2O2 generators is less clear pending additional research, especially in application-like settings.
1. Nardell EA. Fans, filters, or rays? Pros and cons of the current environmental tuberculosis control technologies. Infect Control Hosp Epidemiol. 1993;14(12):681-685. doi:10.1086/646669
2. Nardell EA, Keegan J, Cheney SA, Etkind SC. Airborne infection. Theoretical limits of protection achievable by building ventilation. Am Rev Respir Dis. 1991;144(2):302-306. doi:10.1164/ajrccm/144.2.302
3. Nardell EA. Indoor environmental control of tuberculosis and other airborne infections. Indoor Air. 2016;26(1):79-87. doi:10.1111/ina.12232
4. Centers for Disease Control and Prevention. Guidelines for Environmental Infection Control in Health-Care Facilities (2003). CDC website. Updated July 23, 2019. Accessed February 22, 2022. https://www.cdc.gov/infectioncontrol/guidelines/environmental/index.html
5. Nardell EA. Air disinfection for airborne infection control with a focus on COVID-19: why germicidal UV is essential †. Photochem Photobiol. 2021;97(3):493-497. doi:10.1111/php.13421
6. Wells WF, Wells MW, Wilder TS. The environmental control of epidemic contagion: I. An epidemiologic study of radiant disinfection of air in day schools. Am J Epidemiol. 1942;35(1):97-121. doi:10.1093/oxfordjournals.aje.a118789
7. McLean RL. The effect of ultraviolet radiation upon the transmission of epidemic influenza in long-term hospital patients. Am Rev Resp Dis. 1961;83(2):36-38.
8. Buonanno M, Welch D, Shuryak I, Brenner DJ. Far-UVC light (222 nm) efficiently and safely inactivates airborne human coronaviruses. Sci Rep. 2020;10(1):10285. Published correction appears in Sci Rep. 2021;11(1):19569.
9. Mphaphlele M, Dharmadhikari AS, Jensen PA, et al. Institutional tuberculosis transmission. Controlled trial of upper room ultraviolet air disinfection: a basis for new dosing guidelines. Am J Respir Crit Care Med. 2015;192(4):477-484. doi:10.1164/rccm.201501-0060OC
10. Bergman R, Brenner D, Buonanno M, et al. Air disinfection with germicidal ultraviolet: for this pandemic and the next. Photochem Photobiol. 2021;97(3):464-465. doi:10.1111/php.13424
11. Nardell EA, Bucher SJ, Brickner PW, et al. Safety of upper-room ultraviolet germicidal air disinfection for room occupants: results from the Tuberculosis Ultraviolet Shelter Study. Public Health Rep. 2008;123(1):52-60. doi:10.1177/003335490812300108
12. First MW, Weker RA, Yasui S, Nardell EA. Monitoring human exposures to upper-room germicidal ultraviolet irradiation. J Occup Environ Hyg. 2005;2(5):285-292. doi:10.1080/15459620590952224