key: cord-0982531-lxabtp41 authors: Ereth, Mark H.; Fine, Judith; Stamatatos, Frank; Mathew, Bency; Hess, Donald; Simpser, Edwin title: Health care-associated infection impact with bioaerosol treatment and COVID-19 mitigation measures date: 2021-07-22 journal: J Hosp Infect DOI: 10.1016/j.jhin.2021.07.006 sha: ef6fcdcb9f052740b50b39b18fd902559d509d5f doc_id: 982531 cord_uid: lxabtp41 BACKGROUND: The real-world impact of breathing zone air purification and COVID-19 mitigation measures on health care-associated infections is not well documented. Engineering solutions to treat airborne transmission of disease may yield results in controlled test chambers or single rooms but have not been reported on hospital-wide applications and the impact of COVID-19 mitigation measures on health care-associated infection rates is unknown. AIM: To determine the impact of hospital-wide bioaerosol treatment and COVID-19 mitigation measures on clinical outcomes. METHODS: In a live 124 bed hospital (>100,000 patient days over 30 months) we documented the impact of the step-wise addition of air disinfection technology and COVID-19 mitigation measures to standard multi-modal infection control on particle counts, viral and bacterial bioburden, and health care-associated infection rates. FINDINGS AND CONCLUSION: The addition of air-disinfection technology and COVID-19 mitigation measures reduced airborne ultrafine particles, altered hospital bioburden, and reduced health care-associated infections from 11.9 to 6.6 (per 1,000 patient days) and from 6.6 to 1.0 (per 1,000 patient days) respectively (P< 0.0001, R(2)= 0.86). No single technology, tool, or procedure will eliminate health care-associated infections but the addition of a ubiquitous facility-wide engineering solution at limited expense and with no alteration in patient, visitor, or staff traffic or work flow patterns reduced infections by 45%. A similar impact was documented with the addition of comprehensive, restrictive, and labour and material intensive COVID-19 mitigation measures. We believe this is the first direct comparison between traditional infection control, an engineering solution, and COVID-19 mitigation measures. Bioaerosols that carry bacteria, viruses, and fungi serve as transmission vehicles for diverse infections, including influenza viruses, severe acute respiratory syndrome viruses, and the novel human coronavirus (SARS-CoV-2). Sneezing, coughing, speaking, and simply breathing release and disperse droplets and virus particles [1, 2] . The clinical consequences of bioaerosols involves complex physical and biologic factors, and disinfecting bioaerosols is difficult in any indoor air environment. Cough and sneeze-generating gas clouds with pathogen-bearing droplets can travel up to 8 m, and, once desiccated, the residue or droplet nuclei may stay suspended for hours [3] . Some of the smallest of particles (such as viruses under 30 nm diameter) can invade a room rapidly and may be the most infectious [4, 5] . Even large particles (droplets >100 µm) can be resuspended and aerosolized and may behave like small aerosols due to local environmental [6, 7] . Aerosols and droplets are subject to a person's thermal plume, air currents produced by human traffic, door movements, electrostatic forces, Brownian motion, and convective flows [8] [9] [10] [11] . The constant and turbulent factors within a typical hospital increase broader dissemination and extend settling time of these disease carrying pathogens [12] . There is now evidence to warrant engineering controls that target airborne transmission as part of an overall strategy to limit indoor infectious risk [13] . Components of these strategies include air disinfection, ventilation, enhanced particle filtration, and avoiding recirculation. Traditional infection control strategies such as education, hand washing, surface cleaning, and isolation measures with personal protective equipment (PPE) were primarily developed for large droplet J o u r n a l P r e -p r o o f and surface contamination. Such strategies have limited ability to combat airborne pathogens, especially those continuously suspended within a 0.3 m radius of a nose and mouth, commonly described as the breathing zone. Given the human and environmental factors that constantly move aerosols and resuspend droplets, the concept of clearing a room of all suspended or airborne pathogens is not as simple as just increasing airflow and installing a finer filter [11] . Current technologies that help clean a ducted airstream include high-efficiency particulate air (HEPA) filtration, heating ventilation and air-conditioning (HVAC) modifications, the use of ultraviolet radiation (UV), and various intra-duct oxidizing or ionizing technologies [13] . Benefits attributed to these technologies are often cited from tightly controlled experiments within test chambers, but these are not real-world settings. Each of these technologies may provide benefit within environmental chambers but few have the capacity to continuously counter the numerous and constant infectious and environmental perturbations of a real-world setting. Ideal air disinfection would be easily applied to all areas so that all breathing zone air would be treated and would result in reduced particulate pollution, reduced pathogen contamination, reduced disease transmission, and finally, a reduction in real-world clinical infections. ACTIVE Particle Control™ (APC) (SecureAire, LLC, Dunedin, FL) has been shown to reduce fine and ultrafine airborne particles and pathogens in live operating rooms, reduce bacterial contamination in active hospital compounding pharmacies, and rapidly inactivate or kill the highly resistant anthrax surrogate (Bacillus subtilis) [14, 15] . This novel technology works by local electromagnetic field manipulation [controlled ionization, enhanced polarization, and J o u r n a l P r e -p r o o f controlled particle transport (direction and velocity)]. These forces condition the microparticles (microscopic particles 1-1,000 µm) and pathogens within a space, so they continuously initiate millions of particle-particle (ionization) and particle-molecular (polarization) collisions. These collisions lead to immediate and permanent ionically driven aggregations of fine and ultrafine particles and pathogens into larger particles. With the larger aggregates attaining a critical mass, their transport becomes controlled by airflow and they can be carried by air currents to the particle collector ( Figure 1 ). We sought to determine the impact of adding hospital-wide APC and coronavirus disease (COVID-19) mitigation measures to a multi-modal infection control strategy on particle and pathogen counts, respiratory viral illnesses, and health care-associated infections (HAIs). This work was conducted entirely at St. Mary's Hospital for Children located in Bayside, Queens, NY. St. Mary's is a paediatric post-acute care facility that provides for children with special health care needs and medically complex conditions. Multi-disciplinary teams of paediatric specialists provide care within St. Mary's 124-beds. The comprehensive infection control programme of St. Mary's Hospital operates daily with ongoing and concurrent multi-modal processes to optimize the safety of patients, families, personnel, visitors, and the environment. The programme reports process and outcome surveillance monthly. Key components of the standard programme include handwashing J o u r n a l P r e -p r o o f promotions and signage, infection monitoring, facility antibiogram surveillance, antibiotic stewardship, transmission-based precaution modalities, PPE usage, and scheduled cleaning and disinfection procedures. Automated hand sanitizing surveillance using Bluetooth™ technology captures the compliance of hand hygiene upon entry or exit from the residents' rooms, from bed to bed encounters, and documents the technique and duration of hand hygiene for each staff member. Terminal cleaning of all surfaces with disinfectant upon patient room changes is carried out and portable UV disinfection is conducted in every patient room upon patient discharge and every five to six weeks for routine resident room cleaning and in general common areas ( Figure 2 ). Comprehensive COVID-19 mitigation measures were deployed in late February 2020 and included restricted visitation, screening upon entry, restrictions on volunteers and students, discontinued outpatient services, and a facility-wide comprehensive hand-hygiene programme. Use of an N95 respirator mask, or face mask and visor or shield, during aerosol generating procedures, and universal masking at other times were required ( Figure 2 ). Infection control personnel conducted air quality testing for ultrafine particles (>0.35 µm) and completed air sampling for bacterial and fungus before and after installation of APC. Particle counts were determined using a laser-based particle counter (National Institute of Standards and Technology specifications for measuring particles >0.35 µm and >2.5 µm). Engineering control records including ventilation filter rating, humidity, and temperature were documented by building engineers. Data sources included the electronic medical record, laboratory result record, and hospital census records. Bacterial, fungal, respiratory viral pathogens, total pathogens, and HAIs from all sources were continuously documented by infection control personnel. We examined the predominant infectious etiology and species isolate and determined total infections and infections per 1,000 patient days. We then compared results before and after addition of APC and then with COVID-19 mitigation measures (Table I) . The mean, median, and interquartile ranges were determined for particle counts, bacterial and fungal cultures, respiratory viral illness, and HAIs. We compared laboratory and clinical outcomes with the standard infection control programme, after the addition of APC, and then after the addition of COVID-19 mitigation measures. Comparisons between these three groups were conducted using t-tests, analysis of variance, pairwise Bonferroni multiple comparisons, J o u r n a l P r e -p r o o f and R-square analyses. Statistical significance was determined if the P-value was less than 0.05 (<0.017 for Bonferroni correction). The study was conducted over 30 months with over 100,000 patient days. The average monthly census and general diagnoses on admission did not vary significantly between any of the intervention groups. Patient, facility, and microbial characteristics are summarized in Table I . Three consecutive years were studied. Outcomes from January and February in 2019 and 2020 would have reflected mixed or partially applied APC and COVID-19 procedures and were thus excluded. Calendar months were also chosen in order to eliminate the possible impact of seasonal variation in allergens and influenza illness (Table I, Figure 2 ). Regular infection control procedure monitoring for 2018, 2019, 2020 revealed very high and comparable rates of influenza immunization, handwashing, surface disinfection, droplet and aerosol isolation, and education measures. Mean airborne particle counts (>0.35 µm/ft 3 ) were reduced 12-55% (mean 29%) after installation of APC (P<0.01) (Supplemental Figure 1 ). Following installation of APC there were few-to-no Gram-negative species cultured reflecting a shift in the facility-wide bioburden. None of the fungal isolates were pathogenic post-installation of APC as all were environmental species J o u r n a l P r e -p r o o f commonly found in households and garden areas. In the first 3 months after installation of APC, the respiratory viral illness rate was significantly reduced by >90% (P< 0.001). This varied throughout the 10-month study periodand while the mean respiratory viral illnesses did increase somewhatit remained lower than in previous years and thus was reduced first by APC and second by the COVID-19 mitigation measures (Supplemental Figure 2) . Following the implementation of APC, HAIs were significantly reduced by 45% from an average of 11.9/1,000 patient days for the standard infection control period to an average of 6. The addition of APC was also associated with a 63% reduction in wound infections which did not decline further with COVID-19 mitigation measures. Implementing air disinfection technology was associated with an 89% reduction in tracheitis but did not improve further with COVID-19 mitigation. The incidence of Clostridoides difficile infections did not change after the addition of APC but did decline 90% after the implementation of restrictive COVID-19 measures. The application of APC as an adjunct air disinfection method was associated with significantly reduced HAIs, bacterial and fungal contamination, respiratory viral pathogens, and airborne particles. Further reductions in respiratory and total viral pathogens and HAIs were seen with the addition of comprehensive COVID-19 restriction and mitigation measures. The smallest of airborne pathogens, which are likely the most pathogenic, are the most difficult to capture by traditional filtering methods. APC technology treats and captures all particles equally; volatile organic compounds, viruses, spores, bacteria, smoke, pollen, and other aerosolized allergens [14] . Unlike filters, this solution is agnostic to bioaerosol character or size and is therefore effective on all particles and pathogens (Figure 1 ). The technology is continuously operating and rapidly responds to challenges introduced to a ventilated space by The technology hardware, firmware, and software methodically control the electronic forces applied to fine and ultrafine particles. The mechanism of the clinical impact of APC is multifold. First, by significantly reducing the resident time of pathogens within a hospital room or common area the chance of adequate J o u r n a l P r e -p r o o f inoculum to infect a subject is significantly reduced. Second, pathogens and large droplets that have previously settled on surfaces and are resuspended by human activity become susceptible to APC treatment. Lastly, the technology rapidly and effectively responds to new pathogen challenges generated by coughs, sneezes, or other human activity. The single greatest limitation of this study is also the greatest strength. It was conducted in a real-world live hospital with many uncontrolled variables. As such it is difficult to demonstrate a direct cause and effect between the intervention and a specific outcome for a specific patient. Conversely, the greatest strength of this work is that it was conducted in a live paediatric facility with a diverse patient population with varied co-morbidities, and with patients, clinicians, caregivers, and family coming and going 24/7. All standard infection control procedures, processes, and personnel remained consistent throughout the study as did the patient load and general clinical characteristics of the patient population. Then with the COVID-19 pandemic, additional comprehensive restrictions and mitigation procedures were added. Another concern may be that we only sampled airborne particles and pathogens periodically but not continuously. We did collect viral cultures from symptomatic patients and used laser-based particle counters that are an excellent surrogate for pathogen load especially when measured at 0.4 µm [16] . Critics may insist that such a result cannot be attributed to a single intervention. There are numerous examples of therapies or in this case an engineering solution providing synergistic benefits. APC was added with the express purpose of providing hospital-wide air disinfection. The study was completely conducted by internal personnel, internal sample and laboratory J o u r n a l P r e -p r o o f culture procedures, internal data and analysis, and without outside funding or influence. Further the results speak for themselves in that the interventions overcame all confounding patient and facility variables. Healthy and influenza-infected subjects exhale up to 10,000 particles per litre during tidal breathing with the majority < 0.3 µm in diameter [17] [18] [19] . Normal tidal-volume exhalations, sneezes, and coughs contain short range semi-ballistic emissions that disperse quickly [20] . Most exhaled pathogens are carried in fine particles (0.7-1.0 µm) [21] . In one study, 90% of influenza viral RNA was found in exhaled particles <1.0 µm, with those same fine particles carrying 8 to 9 times the viral copies compared to larger droplets. Lastly pathogens and aerosols can remain suspended in the air for long periods of time [22] with the smallest pathogens remaining resident the longest [9, 23] . Traditional air filtration is effective at removing large particulates such as pollen, mold, and animal dander from the air yet there are limitations. Viable bioaerosols such as bacteria, viruses, and fungi and can be demonstrated on filter media for up to 10 h after aerosolization. In less than 48 h after being installed, 30% of filter media from commercial air handling units have been contaminated with viable picornavirus, coronavirus, and parainfluenza viruses [24] . Air purification technology, such as HEPA, bi-polar ionizers, photo electro-chemical oxidation (PECO), and ultraviolet light (UV), can be beneficial but have significant limitations. High J o u r n a l P r e -p r o o f efficiency particulate air filters effectively remove contaminants once presented to the filter matrix. However, as previously discussed, moving ultrafine particles and pathogens that are indefinitely suspended to the filter remains a limitation. Viruses are roughly 100 times smaller than bacteria, and typically range from 0.004 to 0.1 µm in size. This means even the most efficient air filters would struggle to purge a virus from the air. It has also been demonstrated that Mengovirus can pass through filters commonly used in air handling units and remains infectious upstream and downstream the filter for long periods after aerosolization [25] . Many bi-polar airpurifiers use uncontrolled ionization to bind particles causing pathogens to stick to surfaces within a given space. Recently the generation of noxious chemical by-products and ozone from bi-polar ionization devices has been documented and the technology has been criticized [26, 27] . APC distinguishes itself from bi-polar ionization in that it does not create an electronic corona nor does it generate chemical reactions or ozone [28] . The PECO solution can react with some pollutants to generate dangerous by-products such as formaldehyde, nitrogen dioxide, and carbon monoxide. Disinfection with UV is time-and intensity-dependent and is highly effective on flat surfaces yet does not kill airborne pathogens and the benefits of UV disinfection only persist until human traffic re-enters and contaminates the treated space [29] . Particle size is the most important determinant of aerosol behavior. Particles that are 5 µm or smaller in size can remain airborne indefinitely under most indoor conditions [9, 30, 31] . Immediately respirable aerosols from exhaled breath and coughs are generally fine (<2.5 µm) or ultrafine (<0.1 µm) and once again they appear to carry the largest inoculum of viruses and are thus are the most infectious [32] . Health care-associated infections (HAIs) are the most common complication of health care and are one of the top 10 leading causes of death [33] . Controlling airborne transmission of infection is not simple nor easy. Antiseptic techniques, wearing PPE, and infection prevention procedures are critical. Also critical is deploying engineering solutions that are proven to reduce patient complications [34] . Both the APC and the COVID-19 mitigation measures resulted in similar reductions in the HAI rate. The first solution required a single capital outlay and runs continuously never interrupting staff workflow or inconveniencing patients or family members. The second solution is time, equipment, material, and labour intensive and causes significant interruptions in staff workflow. There is now strong evidence to warrant engineering solutions that target immediately respirable particles (viral laden aerosols) in the 0.7-1.0 µm range [8] . This is even more important since the evidence base for the 1-2 m rule of spatial separation is inconclusive, and we know that aerosols can travel horizontally up to 9 m [35] [36] [37] . Effective engineering solutions must harness the laws of physics to enable clearance of particle pollutants and pathogens from the ventilated space. The repeated assumption is that all airborne pathogens, regardless of size, behave the same and are susceptible to air currents. The incorrect assumption is that air flow alone can transport pathogens to the filter or device where they are completely cleared from the air stream. These assumptions counter the laws of physics which dictate that ultrafine particles are more susceptible to electrostatic forces than gravity or air J o u r n a l P r e -p r o o f currents [9] . Specialized ventilation such as positive and negative pressurized rooms and high air exchanges per hour may help prevent the spread of disease but are expensive to install, carry high energy costs, and still do not fully address the human traffic factor in aerosol dispersion [38] . In the past 18 months the transmission of disease has been actively studied and we more appreciate the complexity of coughs and sneezes and the aerosols they produce. We understand better the impact of human activities on indoor air currents, resuspension of settled droplets, the unintended consequences of air currents in operating rooms, and the broader concepts of pathogen migration [6, 7, 11 ]. Yet little is actually known about the relative contribution of disease transmission by contact, fomite, droplet, or aerosol routes [39] . The work presented here found that ACTIVE Particle Control was associated with reductions in HAIs, wound infection, tracheitis, and respiratory viral infections. Can air disinfection technology impact contact, fomite, and droplet routes of disease transmission? Real-world evidence and three-dimensional modeling have demonstrated that air currents clearly alter dispersion of bacteria in operating rooms [6, 7, 11] . Non-respiratory fomites in virally infected animals are readily aerosolized and airborne [40] . Also, genetically traced and aerosolized Escherichia coli has been demonstrated in adjacent homes demonstrating airborne transmission between built environments [41] . Certainly, some human activities and/or The technology accelerated collisions result in particle agglomeration. The larger coagulated particles and their increased mass are subject to air currents that deliver the same to the collector media. Once collected the highly defined high voltage field induces oxidative stress killing or inactivating any biologic material. Baseline mean health care-associated infection rates (HAIs) with standard infection control (IC) were 11.9/1,000 patient days and were reduced to 6.7/1,000 patients days after ACTIVE Particle Control™ (APC) was implemented (P<0.0001), and were further reduced to 1.0/1,000 patient days after implementation of comprehensive COVID-19 restriction and mitigation measures (COVID) (P<0.0001). Analysis of variance (with and without Bonferroni multiple comparisons), P<0.0001. With each additional infection prevention measure 86% of the variation in HAI rate was due to the mitigation procedure (R 2 = 0.86). Figure 1 : Representative mean ultrafine particle counts. Mean particle counts (>0.35 microns/ft 3 ) before and after ACTIVE Particle Control™ implementation in three representative locations were reduced by 12-55% (mean 29%) (P<0.01). 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