COMPOUND WITH CONFIDENCE: PCCA Membership, $795/month.
Stay current on PCCA news and events, market trends, and all things compounding!
By Yi Liu, PharmD, PhD, PCCA Research Pharmacist; Daniel Banov, RPh, MS, PCCA Director of Research and Development; and Gus Bassani, PharmD, PCCA Chief Scientific Officer; and Matt Martin, PharmD, PCCA Clinical Services Manager
This article was updated: August 7, 2020
The COVID-19 pandemic has dramatically changed everyday life worldwide. It has also shifted the focus of researchers, including PCCA Science. As long as COVID-19 is spreading in communities, everyone is encouraged to practice social distancing and face-covering, regular and thorough hand hygiene, appropriate respiratory hygiene, and good disinfection habits. While people are trying to cope with the changes, we may face some questions in the pharmacy world. For example, what should we do with the dryness and roughness of skin resulting from frequent and diligent hand-washing? Is it possible to use a nasal spray to prevent the virus from entering the nose? What is the efficacy of different masks? We in PCCA Science have been researching published literature and would like to discuss what evidence is currently available regarding these questions.
Hand-Washing with Soap and Water
Most nonmedicated soaps for household and personal cleaning are alkali- or detergent-based and contain fatty-acid esters and sodium or potassium salts. Unlike hand sanitizer that is designed to kill microorganisms, the surfactants in soaps inactivate enveloped viruses such as the new coronavirus, SARS-CoV-2, by inserting into and disrupting the lipid bilayer of the envelope. Then the micelles formed by soap lathering encapsulate the viral debris and lift it from skin with the help of water. Loosely attached microorganisms on hands are also mechanically removed by rubbing and rinsing with water.1 All surfactants have a similar effect in removing contaminants, and the effect is not affected by water temperature.
Nevertheless, soaps and frequent hand-washing may be associated with increased risk of skin-barrier impairment, which presents as rough, dry and scaly skin, sometimes combined with redness (erythema) and a burning sensation.2 Increased pH, decreased skin components and dehydration of skin have been documented after repetitive hand-washing with alkaline soap or detergent.3 The main reason is probably the loss of the “acid mantle” of the stratum corneum (the acidic outer layer of the skin). The acidic nature of the skin surface, having a pH generally between 5.4 and 5.9, is an important aspect of the permeability barrier and acts as a cutaneous antimicrobial defense system.4 While studies have found that using cleansing agents with pH 5.5 can significantly prevent pH elevation and fat loss in skin after washing,5 skin dehydration and detergent penetration through the skin were also found to be significantly higher with soap at 98.6° F (37° C) than at 77° F (25° C.)1,3 Therefore, washing hands with cold water and acidic detergent, especially with a pH of about 5.5, may help to prevent skin irritation and ensure compliance.
One option provided by PCCA is VersaBase® Foam, which is an amino-acid anionic surfactant complex derived from L-glutamic acid and plant-derived fatty acids. It is a mild surfactant, and it has an excellent conditioning effect to the skin, leaving a moisturized feeling without tautness. PCCA members with Clinical Services access can find examples of compounded cleansers with VersaBase Foam in our formula database:
Cleaning the nasal passages with a saline nasal spray has been historically used to reduce symptoms and shorten the duration of disease at the early stage of upper respiratory tract infection (URTI). (Twenty-five percent of URTIs are caused by human coronaviruses.6) So far, there is no evidence supporting any type of nasal spray to effectively protect people from SARS-CoV-2 infection. However, in theory, it transmits by attaching to the epithelial lining of the nasal cavity or mucous membrane of the mouth or eyes, replicating there and further traveling down to the lungs. Nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, are highly enriched with ACE2 receptor expression, which is the SARS-CoV-2 entry gene.7 According to a study analyzing the nasal and throat swabs in COVID-19 patients, the viral load is high on the day of symptom onset and higher in the nose than the throat in both symptomatic and asymptomatic patients.8 This observation resembles the viral shedding pattern of patients with influenza.8 Nasally delivered antiviral therapy may be an option to prevent COVID-19 at the early onset of infection, especially for health care workers who are at risk of exposure.
Researchers investigated hypertonic saline nasal irrigation and gargling in an open-label, randomized, controlled trial, and saw an association with significantly reduced duration of illness, transmission within a household and viral shedding for the common cold.9 Similar results were obtained in two randomized, double-blind, placebo-controlled trials assessing the effectiveness of carrageenan nasal spray in URTIs.6 SARS-CoV-2, like other enveloped viruses, can be inactivated at low pH. For instance, lactic acid and wine vinegar (6% acidity) both have viricidal activity against SARS-CoV in vitro.10,11 An animal study using a nasal spray with pH 3.5 had consistent findings of reduced influenza virus shedding and severity of infection.12 Tolerability of an acidic nasal spray should not be a concern under normal circumstances, as an acidified saline nasal spray with pH 2.5 has been proven safe and tolerable in a clinical trial.13
Researchers in the UK have recently proposed povidone iodine nasal spray as a prophylactic treatment for health care workers during COVID-19.14 There is strong evidence in vitro to support the efficacy of povidone iodine against SARS-CoV-2 and its safety in nasal application.15 Nasodine, a povidone-iodine nasal spray developed for treating URTIs by an Australian company, is currently in a phase III clinical trial. Several clinical trials are currently underway worldwide examining the efficacy of intranasal povidone iodine ranging from 0.5–10% in reducing SARS-CoV-2 viral load.
There are some active pharmaceutical ingredients (APIs) that have gained interest as promising prophylactic agents that can be delivered by the nasal route. It is believed that plasmin can increase the pathogenicity of SARS-CoV-2 through cleaving the S protein on the virus surface, facilitating its binding to ACE2 receptors and subsequent entry into cells.16 Tranexamic acid, an inhibitor of plasmin and its proteolytic activity, is commonly used to stop bleeding, and has shown activity against influenza virus entry in vitro.17 It is now being re-purposed for treatment of COVID-19 in a clinical trial (NCT04338126) based on this mechanism of action. Although the ongoing trial uses oral tranexamic acid for systemic treatment, the tranexamic acid nasal spray targeting viral entry into nasal mucosa may be promising as well.
In addition to the ACE2 receptor, mast cells are also highly enriched in the nasal mucosa, and they play a role in releasing proinflammatory cytokines and exaggerating the “cytokine storm.”18 Mast cell stabilizers, specifically ketotifen — a common ingredient in nasal sprays for rhinitis — may have the potential to lower cytokine release if given both intranasally and orally.19,20 Further clinical studies are needed to explore the clinical value of nasal use of these APIs.
The use of hydrogen peroxide nasal spray has also been discussed as a preventive therapy; however, there is no clinical evidence to prove its efficacy and safety. Hydrogen peroxide is an established viricidal disinfectant and antiseptic effective against SARS-CoV-2, but its activity on nasal mucosa is unknown. The nasal irrigation application was first suggested to treat septic sinuses in the 1910s.21 In a mouse model that was infected with influenza virus, the nasal epithelial cells produced hydrogen peroxide as a protective response.22 In contrast, as a strong oxidizing agent, addition of hydrogen peroxide to the in vitro nasal epithelial cells led to oxidative stress and cell injury.23 The Agency for Toxic Substances and Disease Registry (ATSDR) has warned that inhalation of household-strength hydrogen peroxide (3%) can cause respiratory irritation, while higher strengths may be associated with severe pulmonary injury.24 Therefore, more safety and efficacy studies are needed before recommending hydrogen peroxide nasal spray for COVID-19 prevention.
In spite of a limited number of studies using a nasal spray to prevent COVID-19, there is a great potential to develop an effective therapy delivered by the nasal route to inhibit virus replication at an early infectious stage. Prolonged contact time may be a desired characteristic for such an antiviral nasal spray to improve clinical outcomes. PCCA’s MucoLox™ can provide additional adhesion to the nasal mucous membrane and therefore may improve efficacy of the API. A recent phase II clinical trial conducted by researchers at Brigham and Women’s Hospital (Boston, Massachusetts) has shown the therapeutic benefits of adding MucoLox to a mucous-membrane treatment formulation.25 PCCA members with Clinical Services access can see examples of compounded nasal dosage forms with MucoLox in our formula database:
PCCA’s XyliFos® is another option when choosing a base for nasal formulations. It improves solubilization, moisturization and mucosal adhesiveness. Moreover, XyliFos contains an EGCg-cyclodextrin complex, which may act as a viral-entry inhibitor.26 EGCg has shown some benefits in herpes-simplex-virus and URTI management in multiple clinical trials.27-29 Overall, a nasal spray for COVID-19 is promising and feasible, yet more studies are needed to identify the optimal formulation.
Can SARS-CoV-2 spread through the air? The infectivity of SARS-CoV-2 aerosol and the possibility of airborne transmission has been controversial for months. A recent preprint study completed by a collaborative group of researchers at the University of Nebraska, the National Strategic Research Institute, the University of Illinois and Harvard University revealed the infectious nature of aerosol generated by COVID-19 patients. The study proved the presence of SARS-CoV-2 RNA in aerosols sized < 1 m and 1–4 m that patients produced during respiration, vocalization and coughing. Not only RNA, the aerosols also contained infectious and replicating viral particles.30 These findings support the possibility of airborne transmission as well as the necessity of aerosol prevention measures to reduce the spread of SARS-CoV-2.
Is six feet enough social distance to prevent the spread of SARS-CoV-2? Studies have estimated that one minute of loud talking can generate more than 1,000 virion-containing aerosol particles for an average person.31 Aerosols can float in indoor air for hours, remain infectious and accumulate over time. It takes 12.4 hours for a 1 m aerosol particle to settle to the ground from a distance of eight feet.32 Coughs and sneezes can create thousands of aerosols being propelled over eight feet up to 20 feet, sometimes further.33 Aerosols are found more concentrated in more crowded areas, and they travel following airflows much further than six feet. 34 Therefore, without a face covering, people can still easily inhale aerosols even standing six feet away from others.
What types of face masks are effective? The size of SARS-CoV-2 particles is approximately 50–200 nm in diameter, with an average of 120 nm.30 To determine whether a face mask is suitable to reduce exposure to SARS-CoV-2, the user needs to examine the filtration efficiency of the mask using particles of similar size. ASTM has set an international standard for mask ratings based on their performance with fluid resistance, differential pressure, filter efficiency and flammability. N95 respirators should be reserved for health care workers right now due to the pandemic, and their efficacy has been well defined by National Institute for Occupational Safety and Health (NIOSH) standards. Here, we have summarized the particle filtration levels of surgical masks and homemade masks with different materials to help people identify the right masks according to their needs.
Comparison between Surgical Masks and Homemade Masks
Materials
Filtration Efficiency
Comment
ASTM Level 3 surgical mask
≥ 98% (100 nm particles) 36
Resistance to Synthetic Blood penetration by pressure ≤ 160 mm Hg
ASTM Level 2 surgical mask
Resistance to Synthetic Blood penetration by pressure ≤ 120 mm Hg
ASTM Level 1 surgical mask
≥ 95% (100 nm particles) 36
Resistance to Synthetic Blood penetration by pressure ≤ 80 mm Hg
Surgical mask
(not ASTM-rated)
89.52% ± 2.65%; 37
63% – 96% 38,39
Fluid resistance level is unknown
Dental masks
10% – 47% 38
Comparable breathability with surgical masks
100% cotton
50.85% ± 16.81% 37
Scarf
48.87% ± 19.77% 37
Tea towel
72.46% ± 22.60% 37
Poor breathability
Pillowcase
57.13% ± 10.55% 37
Best breathability
Vacuum cleaner bag
85.95% ± 1.55% 37
Very poor breathability
Cotton mix
70.24% ± 0.08% 37
Linen
61.67% ± 2.41% 37
Silk
54.32% ± 29.49% 37
In the fabric assessments, a single layer of fabric was tested. The masks were tested at unworn condition. If the materials were worn for a couple of hours and contained water vapor, the filtration efficacy would be different. Filtration efficacy of non-ASTM surgical mask and homemade masks were evaluated using a bacteriophage of 23 nm in diameter and delivered at 30 L/min, which is about 3–6 times per minute the ventilation of a human at rest or doing light work, but is less than 0.1 the flow of an average cough.37
Recently, a group of researchers in Hong Kong compared the levels of respiratory droplets (particles > 5 m) and aerosols (particles ≤ 5 m) generated from URTI patients who were wearing a face mask or not while sitting for 30 minutes with normal breathing and coughing. The findings indicate that wearing a face mask can effectively reduce the emission of coronavirus particles into the environment in both respiratory droplets and aerosols. The face masks used were non-ASTM rated, standard, three-layer procedure masks not expected to be resistant to fluid.40
Because the majority of the general public is wearing cloth-based face coverings, a group of engineers at Florida Atlantic University has mimicked coughs and sneezes and qualitatively visualized the respiratory jets as well as the performance of different mask materials in a lab. They found that a well-fitted, homemade mask with multiple layers of quilting fabric (70 thread count) is as effective as a commercial cone face mask in reducing the distance of respiratory jets (from eight feet when uncovered to less than eight inches when using masks). Loosely folded face masks or bandana-style coverings have minimal effectiveness in limiting the spread of aerosolized respiratory jets, but are still able to reduce the distance to within six feet, compared to an uncovered cough that expelled more than eight feet. Another important finding is that a well-fitted construction is more important than a higher thread count by itself to ensure the effectiveness of a mask.41
Multiple other studies have consistently shown that any type of mask can significantly reduce aerosol exposure compared to not wearing a mask. The best practice should be combining all preventive measures, including social distancing and hygiene, and not solely relying on face masks or social distancing.
Yi Liu, PharmD, PhD, is a research pharmacist in the Research and Development department at PCCA. She joined PCCA as a clinical pharmacy researcher in the Clinical Services department in 2018 and started her current role in 2019. Yi graduated from Ohio University with a PhD in molecular and cellular biology in 2012. She also worked as a postdoctoral research fellow in the Houston Methodist Research Institute for three years prior to starting pharmacy school. Yi received her PharmD from the University of Houston College of Pharmacy in 2019.
Daniel Banov, MS, RPh, PCCA Director of Research and Development, has over 20 years of hands-on experience in pre-formulation, formulation and reformulation of a variety of dosage forms. He has extensively worked on developing novel techniques for skin-permeation enhancement. Daniel currently has 17 granted U.S. patents and many others pending. Before joining the PCCA team, Daniel was the Director of Fórmula Médica Compounding Pharmacy in São Paulo, Brazil, and was a university teacher and a cosmetic developer and consultant for physicians, spas and aestheticians. He also is the founder of the Anti-aging Society in Brazil.
Gus Bassani, PharmD, PCCA Chief Scientific Officer, has been with PCCA since September 2002. Prior to that, he was a formulation pharmacist in the product development lab of a veterinary pharmaceutical company. He has worked in multiple pharmacy practice settings and has taught extemporaneous compounding principles to pharmacy students. Gus earned his Doctor of Pharmacy degree from the Drake University College of Pharmacy and Health Sciences. He is a member of the 2015–2020 United States Pharmacopeia Council of Experts – Compounding Expert Committee, and served on the 2012–2014 Drake University College of Pharmacy and Health Sciences National Advisory Council. He is a member of the American Pharmacists Association, Alliance for Pharmacy Compounding, and American Association of Pharmaceutical Scientists.
Matt Martin, PharmD, is the Clinical Services Manager at PCCA. He joined the PCCA Clinical Services department in September 2014. Matt graduated from Morehead State University with a BS in Chemistry in 2002, and received his PharmD from the University of Kentucky College of Pharmacy in 2006. Prior to joining the PCCA team, Matt worked in pharmacy compounding for more than eight years, and has experience with both sterile and nonsterile preparations.
References
1. Kampf, G., & Kramer, A. (2004). Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs. Clinical Microbiology Reviews, 17(4), 863–93. https://doi.org/10.1128/cmr.17.4.863-893.2004
2. Kampf, G., & Ennen, J. (2006). Regular use of a hand cream can attenuate skin dryness and roughness caused by frequent hand washing. BMC Dermatology, 6(1). https://doi.org/10.1186/1471-5945-6-1
3. Davies, M. A. Cleansing-induced changes in skin measured by in vivo confocal raman spectroscopy. Skin Research & Technology, 26(1), 30–38. https://doi.org/10.1111/srt.12760
4. Schmid-Wendtner, M.-H., & Korting, H. C. The pH of the skin surface and its impact on the barrier function. Skin Pharmacology and Physiology, 19(6), 296–302. https://doi.org/10.1159/000094670
5. Gfatter, R., Hackl, P., & Braun, F. Effects of soap and detergents on skin surface pH, stratum corneum hydration and fat content in infants. Dermatology, 195(3), 258–62. https://doi.org/10.1159/000245955
6. Koenighofer, M., Lion, T., Bodenteich, A., Prieschl-Grassauer, E., Grassauer, A., Unger, H., Mueller, C. A., & Fazekas, T. (2014). Carrageenan nasal spray in virus confirmed common cold: Individual patient data analysis of two randomized controlled trials. Multidisciplinary Respiratory Medicine, 9(1), 57. https://doi.org/10.1186/2049-6958-9-57
7. Sungnak, W., Huang, N., Becavin C., Berg, M. (2020). SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways. arXiv:2003.06122v1 [q-bio.CB] Preprint.
8. Zou, L., Ruan, F., Huang, M., Liang, L., Huang, H., Hong, Z., Yu, J., Kang, M., Song, Y., Xia, J., Guo, Q., Song, T., He, J., Yen, H.-L., Peiris, M., & Wu, J. (2020). SARS-CoV-2 viral load in upper respiratory specimens of infected patients. New England Journal of Medicine, 382(12), 1177–1179. https://doi.org/10.1056/NEJMc2001737
9. Ramalingam, S., Graham, C., Dove, J., Morrice, L., & Sheikh, A. (2019). A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Scientific Reports, 9(1), 1015. https://dx.doi.org/10.1038%2Fs41598-018-37703-3
10. Rabenau, H. F., Cinatl, J., Morgenstern, B., Bauer, G., Preiser, W., & Doerr, H. W. (2005). Stability and inactivation of SARS coronavirus. Medical Microbiology and Immunology, 194(1–2):1–6. https://doi.org/10.1007/s00430-004-0219-0
11. United States Environmental Protection Agency. (2020, April 16). List N: Disinfectants for use against SARS-CoV-2. https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2
12. Rennie, P., Bowtell, P., Hull, D., Charbonneau, D., Lambkin-Williams, R., & Oxford J. (2007). Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection. Respiratory Research, 8(1), 38. https://doi.org/10.1186/1465-9921-8-38
13. Ryan, W. R., & Hwang, P. H. (2010). Safety of a preservative-free acidified saline nasal spray: A randomized, double-blind, placebo-controlled, crossover clinical trial. Archives of Otolaryngology — Head & Neck Surgery. 136(11), 1099–1103. https://doi.org/10.1001/archoto.2010.179
14. Kirk-Bayley, J., Combes, J., Sunkaraneni, S., & Challacombe, S. (2020). The use of povidone iodine nasal spray and mouthwash during the current COVID-19 pandemic may reduce cross infection and protect healthcare workers. SSRN. http://dx.doi.org/10.2139/ssrn.3563092
15. Ramezanpour, M., Smith, J. L. P., Psaltis, A. J., Wormald, P. J., & Vreugde S. (2020). In vitro safety evaluation of a povidone-iodine solution applied to human nasal epithelial cells. International Forum of Allergy & Rhinology. Advance online publication. https://doi.org/10.1002/alr.22575
16. Hatachi , Y., Kubo, H., Yasuda , H., Nishimura, H., Nagatomi, R., & Yamaya, M. (2010). Tranexamic acid inhibits infection of seasonal human influenza virus in airway epithelial cells.American Journal of Respiratory and Critical Care Medicine, 181. https://doi.org/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A6191
17. Ji, H.-L., Zhao, R., Matalon S., & Matthay M. A. (2020). Elevated plasmin(ogen) as a common risk factor for COVID-19 susceptibility. Physiological Reviews, 100(3), 1065–1075. https://doi.org/10.1152/physrev.00013.2020
18. Kritas, S. K., Ronconi, G., Caraffa, A., Gallenga, C. E., Ross, R., & Conti, P. (2020). Mast cells contribute to coronavirus-induced inflammation: New anti-inflammatory strategy. Journal of Biological Regulators and Homeostatic Agents. Advance online publication. https://doi.org/10.23812/20-editorial-kritas
19. Graham A. C., Temple, R. M., & Obar, J. J. (2015). Mast cells and influenza A virus: Association with allergic responses and beyond. Frontiers in Immunology, 6. https://dx.doi.org/10.3389%2Ffimmu.2015.00238
20. Enkirch, T., Sauber, S., Anderson, D. E., Gan, E. S., Kenanov, D., Maurer-Stroh, S., & von Messling, V. (2019). Identification and in vivo efficacy assessment of approved orally bioavailable human host protein—Targeting drugs with broad anti-influenza A activity. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.01097
21. Laurie, R. D. (1910). Continuous irrigation with hydrogen peroxide as a treatment for septic sinuses, etc. The Hospital, 47(1226), 515.
22. Kim, H. J., Seo, Y. H., An, S., Jo, A., Kwon, I. C., & Kim, S. (2018). Chemiluminescence imaging of Duox2-derived hydrogen peroxide for longitudinal visualization of biological response to viral infection in nasal mucosa. Theranostics, 8(7), 1798–1807. https://doi.org/10.7150/thno.22481
23. Jia, M., Chen, X., Liu, J., & Chen, J. (2018). PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways. Molecular Medicine Reports, 17(1), 571–579. https://doi.org/10.3892/mmr.2017.7912
24. Agency for Toxic Substances and Disease Registry. (2014, October 21). Medical management guidelines for hydrogen peroxide. https://www.atsdr.cdc.gov/toxfaqs/tf.asp?id=305&tid=55
25. Villa, A., Sankar, V., Bassani, G., Johnson, L. B., & Sroussi, H. (in press). Dexamethasone solution and dexamethasone in MucoLox for the treatment of oral lichen planus: A preliminary study. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. https://doi.org/10.1016/j.oooo.2020.02.014
26. Isaacs, C. E., Wen, G. Y., Xu, W., Jia, J. H., Rohan, L., Corbo, C., Di Maggio, V., Jenkins, E. C., Jr., & Hillier, S. (2008). Epigallocatechin gallate inactivates clinical isolates of herpes simplex virus. Antimicrobial Agents and Chemotherapy, 52(3), 962–970. https://doi.org/10.1128/aac.00825-07
27. Zhao, M., Zheng, R., Jiang, J., Dickinson, D., Fu, B., Chu, T.-C., Lee, L. H., Pearl, H., & Hsu, S. (2015). Topical lipophilic epigallocatechin-3-gallate on herpes labialis: A phase II clinical trial of AverTeaX formula.Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 120(6), 717–724. https://doi.org/10.1016/j.oooo.2015.08.018
28. Yamada, H., Takuma, N., Daimon, T., & Hara, Y. (2006). Gargling with tea catechin extracts for the prevention of influenza infection in elderly nursing home residents: A prospective clinical study. Journal of Alternative and Complementary Medicine, 12(7), 669–672. https://doi.org/10.1089/acm.2006.12.669
29. Furushima, D., Nishimura, T., Takuma, N., Iketani, R., Mizuno, T., Matsui, Y., Yamaguchi, T., Nakashima, Y., Yamamoto, S., Hibi, M., & Yamada, H. (2020). Prevention of acute upper respiratory infections by consumption of catechins in healthcare workers: A randomized, placebo-controlled trial. Nutrients, 12(1), 4. https://dx.doi.org/10.3390%2Fnu12010004
30. Santarpia, J. L., Herrera, V. L., Rivera, D. N., Ratnesar-Shumate, S., Reid, S. P., Denton, P. W., Martens, J. W. S., Fang, Y., Conoan, N., Callahan, M. V., Lawler, J. V., Brett-Major, D. M., & Lowe, J. J. (2020). The infectious nature of patient-generated SARS-CoV-2 aerosol. MedRxiv. https://doi.org/10.1101/2020.07.13.20041632
31. Stadnytskyi, V., Bax, C. E., Bax, A., & Anfinrud, P. (2020). The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission.Proceedings of the National Academy of Sciences (PNAS), 117(22), 11875–11877. https://doi.org/10.1073/pnas.2006874117
32. Tellier, R., Li, Y., Cowling, B. J., & Tang J. W. (2019). Recognition of aerosol transmission of infectious agents: A commentary. BMC Infectious Diseases, 19. https://doi.org/10.1186/s12879-019-3707-y
33. Morawska, L., & Cao, J. (2020). Airborne transmission of SARS-CoV-2: The world should face the reality. Environment International, 139. https://doi.org/10.1016/j.envint.2020.105730
34. Liu, Y., Ning, Z., Chen, Y., Guo, M., Liu, Y., Gali, N. K., Sun, L., Duan, Y., Cai, J., Westerdahl, D., Liu, X., Xu, K., Ho, K.-F., Kan, H., Fu, Q., & Lan, K. (2020). Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature, 582, 557–560. https://doi.org/10.1038/s41586-020-2271-3
35. Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X., & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. The Lancet, 395(10223), 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7
36. ASTM International. (2011). ASTM F2100-11: Standard specification for performance of materials used in medical face masks . https://doi.org/10.1520/F2100-11
37. Davies, A., Thompson, K.-A., Giri, K., Kafatos, G., Walker, J., & Bennett, A. (2013). Testing the efficacy of homemade masks: Would they protect in an influenza pandemic? Disaster Medicine and Public Health Preparedness, 7(4), 413–418. https://doi.org/10.1017/dmp.2013.43
38. Oberg, T., & Brosseau, L. M. (2008). Surgical mask filter and fit performance. American Journal of Infection Control, 36(4), 276–282. https://doi.org/10.1016/j.ajic.2007.07.008
39. Shakya, K. M., Noyes, A., Kallin, R., & Peltier, R. E. (2017). Evaluating the efficacy of cloth facemasks in reducing particulate matter exposure. Journal of Exposure Science & Environmental Epidemiology, 27(3), 352–357. https://doi.org/10.1038/jes.2016.42
40. Leung N. H. L., Chu, D. K. W., Shiu, E. Y. C., Chan, K.-H., McDevitt, J. J., Hau, B. J. P., Yen, H.-L., Li, Y., Ip, D. K. M., Peiris, J. S. M., Seto, W.-H., Leung, G. M., Milton, D. K., & Cowling, B. J. (2020, April 3). Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Medicine. https://doi.org/10.1038/s41591-020-0843-2
41. Verma, S., Dhanak, M., & Frankenfield, J. (2020). Visualizing the effectiveness of face masks in obstructing respiratory jets. Physics of Fluids, 32(6). https://doi.org/10.1063/5.0016018