key: cord-0942481-r2wy2kuo
authors: Patel, Bhavesh; Forzani, Erica; Lowell, Amelia; McKay, Kelly; Karam, Karam Abi; Pandian, Adithya Shyamala; Pyznar, Gabriel; Xian, Xiaojun; Serhan, Michael
title: Self-contained system for mitigation of contaminated aerosol sources of SARS-CoV-2 
date: 2021-02-24
journal: Res Sq
DOI: 10.21203/rs.3.rs-237873/v1
sha: a57bab1fbfa7ccbf4b037f2ae31815ae2da4b5ea
doc_id: 942481
cord_uid: r2wy2kuo

Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing (1-3) and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected, (4) eliminating transmissions from infection sources is also important to prevent disease transmission. Supportive therapies for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pneumonia such as oxygen supplementation, nebulizers and non-invasive mechanical ventilation all carry an increased risk for viral transmission via aerosol to healthcare workers. (5-9) In this work, we study the efficacy of five methods for self-containing aerosols emitted from infected subjects undergoing nebulization therapies with a diverse spectrum on oxygen delivery therapies. The work includes five study cases: Case I: Use of a Full-Face Mask with biofilter in bilevel positive airway pressure device (BPAP) therapy, Case II: Use of surgical mask in High Flow Nasal Cannula (HFNC) therapy, Case III: Use of a modified silicone disposable mask in a HFNC therapy, Case IV: Use of a modified silicone disposable mask with a regular nebulizer and normal breathing, Case V: Use of a mitigation box with biofilter in a Non-Invasive Positive Pressure Ventilator (NIPPV). We demonstrate that while cases I, III and IV showed efficacies of 98-100%; cases II and V , which are the most commonly used, resulted with significantly lower efficacies of 10-24% to mitigate the dispersion of nebulization aerosols. Therefore, implementing cases I, III and IV in health care facilities may help battle the contaminations and infections via aerosol transmission during a pandemic.

modified silicone disposable mask in a HFNC therapy, Case IV: Use of a modified silicone disposable mask with a regular nebulizer and normal breathing, Case V: Use of a mitigation box with biofilter in a Non-Invasive Positive Pressure Ventilator (NIPPV). We demonstrate that while cases I, III and IV showed efficacies of 98-100%;

cases II and V, which are the most commonly used, resulted with significantly lower efficacies of 10-24% to mitigate the dispersion of nebulization aerosols. Therefore, implementing cases I, III and IV in health care facilities may help battle the contaminations and infections via aerosol transmission during a pandemic.

The coronavirus (COVID-19) pandemic has already infected over 45 million across the world and is responsible for more than 1.1 million deaths as of November 1st 2020. 10 The disease is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 11 . The mortality rate is estimated to be nearly 5% for those between the ages of 45-64 years old and a striking 19.1% for those in the 75+ age group 12 . Clearly, SARS-CoV-2 is a massive risk given the widespread transmission of the virus.

To date, there is a plethora of evidence demonstrating that SARS-CoV-2 transmission occurs fundamentally from the spread of viral pathogens in the infected host's respiratory system to other susceptible hosts in contact with droplets, aerosols and fomites. 3, 7, 13, 14 An aerosol is a suspension of fine particles (which can include viral pathogens) in an airborne liquid mist and can be transported through ventilation systems (e.g. AC) since it is not strongly affected by gravity 3 . Since SARS-CoV-2's effective size is ~100 nm 11, 15 , it can be encapsulated within aerosols from the respiratory system of an infected person, presenting a major health risk to the environment of any building where a SARS-CoV-2 infected person might reside or be present 1, 3 . Ninety-nine percent of aerosols produced by humans, regardless of age, sex, weight and height are less than 10 m 2, 3 . This is concerning since the smaller the aerosol, the longer it takes to settle increasing the risk of inhaling the contaminated aerosols by other individuals 16 .

For example, an 0.5 m aerosol takes 41 hours to settle 17 . In case of SARS-CoV-2, the viruses can be viable on a surface for up to 3 days 18 . Researchers have found SARS-CoV-2 14 with virulent activity 3 in collected aerosol particles from 0.2 m to 10 m, which is a serious concern for the spread of the disease through air conditioning (AC) systems 7, 19 . More recently CDC has recognized the importance of the transmission potential of SARS-CoV-2 via aerosols 20 . The groundbreaking evidences strongly indicates the need of aerosol mitigation to safeguard the public and public spaces of the populations.

In the present work, we target the mitigation of aerosol dispersion during nebulization treatments to provide a means of safe treatment for a respiratory disease such as COVID-19. This treatment causes a high risk of spreading pathogens due to the nebulization therapy generating aerosols with sizes less than 10 m 21 , with emphasis on aerosol portions that do not impact the alveolar area, but remain in the dead space of the respiratory system (including nose and mouth) in contact with infectious areas and are exhaled into the environment 9 . Fig. 1a illustrates the problem by showing aerosol particle counts / feet 3 transient over time inside a room with a COVID-19 patient during a nebulization therapy. The measurement was carried out in a Room of 17' x 13.6' x 9', equipped with a small bathroom of 4' x 6.25' x 9' in the back and an air ventilation rate, which is purposely set at ~20 air changes per hour -1 to minimize transmission of the disease via aerosols 17, 19 . The measurement was performed with a total of 3 aerosol sensors located at 3 (DL-1), 6 (DL-2) and 9 feet (DL-3) away from the subject as shown in Fig. 1b . The sensors were able to detect aerosol particles equal to or larger than 0.19 m (see Supplementary Information, Fig. 1) . The COVID-19 patient was assisted through an oxygen delivery therapy via a high flow nasal canula (HFNC) at 60 L/min. A nebulization therapy and an exercise therapy were delivered to the patient under the supervision of a respiratory therapist during the measurement. The nebulization included a total 3 ml solution containing 2.7 ml of Albuterol and 0.3 mL of saline physiological solution delivered through a Piezoelectric Based Nebulizer 22 . The subject did not wear any mask to mitigate the aerosol dispersion. As it can be observed, significant particle counts / feet 3 were detected above the baseline level of the room, typically at ~ 7,400 counts / feet 3 (for 0.2 m -5m size count). During nebulization, the peak level was 365 times greater than the baseline level, and the particles clear out from the room 20 min after the completion of the nebulization. In addition, the proactive respiratory therapy executed by a therapist and patient's breathing exercises under various conditions did not produce detectable aerosol-particle counts. Further, the action of flushing the bathroom toilet did not produce a particle count on the closest particle counter located 6 feet from the bathroom since the bathroom was small and had its own ventilation system with air exchange rate of ~20 h -1 . This seminal data indicates the nebulization therapies in COVID-19 patients should be targeted as a main source of potential contaminated aerosol in the environment.

Aerosol spreading patterns are dependent on air exchange rates and ventilation streams of the room, the mechanism of nebulizers, and environmental (e.g. temperature and humidity) conditions. In fact, Fig. 1a indicates that the spatial distribution of the aerosol in the room is counterintuitive. Although the aerosol concentration at 3 feet was the highest, the peak concentration at 9 feet was 1/3 larger than the corresponding peak at 6 feet location. In order to solve the problem of highly variable and unpredictable aerosol patterns, we mitigate the dispersion by DIRECTLY attacking the problem at the point of contaminated dispersion source and studying the effect of different mitigation systems that could potentially self-contain nebulizer aerosol dispersions. Fig. 2a- 

The peak and area efficacies are evaluated for curves taken at 3, 6 and 13 feet with experimental setup similar to the one shown in [Will appear in online pdf and full-text version online. Do not exceed 3000 words.

Subdivide using headings, continue references from above]

The particles and aerosols generated during the nebulization procedures are assessed using the following commercial optical particle counters: MET ONE HHPC2+ from Beckman Coulter, and Dylos DC1100 Pro and Dylos DC1700 from Dylos Corporation, CA. MET ONE HHPC2+ particle counter provides reading for two ranges of particle sizes: 0.5 m and 5.0 m, which typical correspond to measuring particles 0.5 m and 5.0 m, respectively. Dylos DC1100 Pro and Dylos DC1700

particle counters provide readings for particle sizes of 0.5 m and 2.5 m, which typical correspond to measuring particles  0.5 m and  2.5 m, respectively. The sensors from Dylos DC1100 Pro and Dylos DC170 have identical sensing chambers but differ in the way they are powered. While Dylos DC1100 Pro is powered with a power adapter, Dylos DC1700 can be battery operated.

To decide on the best particle counters for this study, two additional particle counters were evaluated. These include: Dylos DC1100 from Dylos Corporation, CA with a capacity to detect to two ranges of particles: 1.0 m and 5.0 m (representing detection to  1.0 m and  5.0 m, respectively), and Dusttrak DRX aerosol monitor from TSI Incorporated with a capacity to detect Aerosol concentration range 0.001 to 150 mg/m 3 .

Evaluation of all above-mentioned particle counters were performed in a sensing chamber using pure polystyrene particles (Bang Laboratories, Inc.) of size 0.19 µm suspended in ethanol. The particles were aerosolized with the mechanical nebulizer and introduce to a sensing chamber with the aid of a small fan integrated in the chamber inlet port. Different particle aerosol concentrations were created by aerosolizing different volumes from 0.1 mL to 3.0 mL. The sensitivity of the different particle counters to detect 0.19-µm polystyrene aerosol particles was evaluated and are shown in Supplementary Information, Fig. 1A For sake of simplification, we refer to MET ONE HHPC2+ particle counter as "MO sensor", and to Dylos DC1100 and DC1700 as "DL sensor".

Three different rooms were used in the study: 

A total of 6 human test subjects participated in this study. All methods discussed 

Before starting the testing with human subjects, and the different oxygen delivery and mitigation methods, three MO sensors and one DL sensor were positioned in the simulation room at 3, 6, and 13 feet from a piezoelectric nebulizer with 3 mL of 0.19 µm polystyrene particles solution in ethanol, and a nebulization was delivered to the mannequin with a non-invasive positive pressure ventilator (NIPPV) and no aerosol mitigation system connected to it. Supplementary Information, Fig. 3A -B show the corresponding particle concentration profiles, indicating a clear peak after the initiation of the nebulizer, which corroborated the capacity of MO and DL sensors to capture aerosol plumes from nebulization within a room (simulation room 1) with a high air exchange rate (20 h -1 ).

The application of the mitigation methods to different oxygen therapies rendered five study cases described below.

Case I: The test subject used of a Full-Face Mask in bilevel positive airway pressure device (BPAP) therapy. The system was tested with and without the use of a biofilter located in its outlet (Fig. 3a-I) . and without a surgical mask as mitigation system (Fig. 3a-II) . Case IV: The test subject was breathing naturally without the help of any oxygen therapy and was tested with and without the modified silicone mask + biofilter + fan as mitigation system (Fig. 3a-IV) . Case V: The mannequin was ventilated with a Full-Face Mask connected to a Non-Invasive Positive Pressure Ventilator (NIPPV) and was tested with and without a mitigation box that had a biofilter attached to it as mitigation system (Fig. 3a-V) . The mitigation box design was inspired on the isolation hood that has gained attention with the focus of mitigation SARS-CoV-2 pathogens 23 . The nebulization therapy of 3 ml saline physiological solution was delivered through the Piezoelectric Based

Nebulizer. The experiments were carried out in the simulation room 1 equipped with a total of six sensors: i) two sensors MO-1 and DL-1 at 3 feet distance, ii) two sensors the test subject. Supplementary Information, Fig. 8A -C show detailed particle concentration profiles over time assessed at baseline with no nebulization, with nebulization and no mitigation, and with nebulization and mitigation at different distances. Supplementary Information, Fig. 7D -E shows an overlapped particle concentration profiles over time for all sensor locations with and without modified mitigation box, respectively.

The oxygen delivery methods practiced in this study included the following specifications:BiPAP: Full-Face Mask was used to deliver 21% of O2 and 30 L/min of air flow through BPAP ventilator to test subjects. Respironics V60 by Philips provided a non-invasive bilevel positive airway pressure breathing support. Amara 

To mitigate the aerosol spread from the test subject the four different types of mitigations had the following specifications: of Breezing TM mask. The mask is also integrated with a biofilter in the exhalation tube followed by a battery-operated fan (Mouser Electronics).

A plastic box drilled two holes with each at opposite ends fitted with one-way air flow valve to provide one directional ventilation and this box is fitted with 2 MIL plastic curtains that runs throughout the test subject's body to reduce the leak of aerosols.

The air flowing in and out of the room is an important parameter as it is a major factor affecting the dispersion of aerosol. Increasing air exchange rates improves the room's capability of eliminating aerosols and can be determined by the declining slope of particles being vented out from the room 15 . To determine the air exchange rate in the tested room, the room was filled with CO2 gas, and the CO2 gas concentration was monitored over time with a carbon dioxide sensor (Telaire by GE).

The declining slope of recorded CO2 levels yields air exchange rates of 20 hr -1 for the simulation room 1 and patient room, and 2-3 hr -1 for simulation room 2.

Does COVID-19 spread thorugh droplets alone? Front

Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management

Aerosol and Surface Transmission Potential of SARS-CoV-2. medRxiv 2020.03.23

Rationale for universal face masks in public against COVID-19

Role of ventilation in airborne transmission of infectious agents in the built environment -a multidisciplinary systematic review. Indoor Air

Improving natural ventilation in hospital waiting and consulting rooms to reduce nosocomial tuberculosis transmission risk in a low resource setting

Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission

Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19

WHO WHO International Weekly Epidemiological Update

Ysrafil Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response

Data Tracker: Maps, charts, and data provided by CDC

?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcorona virus%2F2019-ncov%2Fcases-updates%2Fcases-inus.html#cases_casesper100klast7days

Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors

Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

Particle sizes of infectious aerosols: implications for infection control

Generation and behavior of airborne particles

The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission

COVID-19 Outbreak and Hospital Air Quality: A Systematic Review of Evidence on Air Filtration and Recirculation

CDC Scientific Brief: SARS-CoV-2 and Potential Airborne Transmission

Measurement of the size and charge distribution of sodium chloride particles generated by an Aerobe Pro® pharmaceutical nebulizer

Physicochemical Aspects and Efficiency of Albuterol Nebulization: Comparison of Three Aerosol Types in an

Intensive care unit isolation hood decreases risk of aerosolization during noninvasive ventilation with COVID-19