НАУЧНО-ПРАКТИЧЕСКИЙ ЖУРНАЛ

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№1-2(5) 2022

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DOI 10.37219/2528-8253-2022-1-78

Huijghebaert Suzy, Hoste Levi, Vanham Guido
Основи фармакології сольових розчинів для гігієни порожнини носа або дихальних шляхів під час COVID-19
Suzy Huijghebaert
Independent Research Support, La Hulpe, Belgium
s.huijghebaert@scarlet.be; s.huijghebaert@gmail.com; OralMedDevs@gmail.com

Levi Hoste
Pediatric Pulmonology, Infectious Diseases and Immunology, Ghent University Hospital, Ghent, Belgium
Primary Immunodeficiency Research Lab, Center for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium

Guido Vanham
Department of Biomedical Sciences, Institute of Tropical Medicine and University of Antwerp, Antwerp, Belgium

Аннотация

Призначення: Промивання порожнини носа або розпилення аерозолю ізотонічного чи гіпертонічного сольового розчину є традиційним методом догляду за дихальними шляхами або порожниною носа. Нещодавнє невелике дослідження, проведене у амбулаторних пацієнтів із COVID-19 без гострого респіраторного дистрес-синдрому показало суттєве зникнення симптомів. Тому ми проаналізували фармакологічні/фармакодинамічні ефекти ізотонічного або гіпертонічного сольового розчину по відношенню до інфекції SARS-CoV-2 та респіраторної допомоги.
Методи: Змішаний метод пошуку.
Отримані результати: Завдяки своїм зволожуючим властивостям фізіологічний розчин сприяє кращому розподілу рідини, що вистилає альвеоли, і, як було показано, знижує біоаерозольне та вірусне навантаження. Сольовий розчин зволожує респіраторний епітелій і перетворює слиз у гель, сприяє биттю війок і покращує мукоциліарний кліренс. Коронавіруси та SARS-CoV-2 пошкоджують війчастий епітелій у порожнині носа та дихальних шляхах. Сольовий розчин пригнічує реплікацію SARS-CoV-2 у клітинах Vero; можливі взаємодії включають вірусний механізм проникнення ACE2 (залежна хлорид конфігурація ACE2), фурин і 3CLpro (інгібування NaCl) і натрієвий канал ENaC. Сольовий розчин змінює активність мієлопероксидази в епітеліальних або фагоцитарних клітинах з утворенням хлорноватистої кислоти. Клінічно обробка порожнини носа чи дихальних шляхів фізіологічним розчином зменшує симптоми сезонних коронавірусів та інших вірусів застуди. Його використання у вигляді аерозолю знижує частоту госпіталізацій з приводу бронхіоліту у дітей. Попередні дані свідчать про зменшення симптомів у пацієнтів із симптоматикою COVID-19, якщо введення фізіологічного розчину починається протягом 48 годин після появи перших симптомів.
Висновки: Сольовий розчин взаємодіє на різних рівнях, пов'язаних з гігієною порожнини носа або дихальних шляхів (промивання носа, полоскання горла або аерозоль). Якщо його використовувати з моменту появи симптомів застуди, він може бути корисним доповненням до втручань першої лінії при COVID-19. Бажано провести формальну оцінку при легкому ступені COVID-19, щоб встановити ефективність та оптимальні схеми лікування.

Ключевые слова

Сольовий розчин, Хлорид натрію, SARS-CoV-2, COVID-19. Мукоциліарний кліренс, Гострий респіраторний дистрес-синдром.


Литература

  1. HNO-Ärzte im Netz (2020) Herausgegeben vom Deutschen Berufsverband der Hals-Nasen-Ohrenärzte e.V.) Tipps zur richtigen Nasenpflege [Tipps for adequate nasal care]. https://www.hno-aerzte-imnetz.de/unsere-sinne/hno-hygiene/tipps-zur-richtigennasenpflege.html. Accessed 19 June 2020
  2. Lungenartze im Netz (Lung doctors in the Net) (2020) Einfaches Inhalieren kann Tröpfcheninfektion effektiv eindämmern. [Simple inhalation can limit efficiently droplet infection] https://www.lungenaerzte-im-netz. de/news-archiv/meldung/article/einfaches-inhalierenkann-troepfcheninfektion-effektiv-eindaemmern/. Accessed 19 June 2020
  3. Praxisvita (das Portal für Gesundheit & Medizin) (2020) Inhalieren bei Corona: Wie wirksam ist das Hausmittel? [Inhalation during Corona; How effective is this home remedy?] https://www.praxisvita. de/coronavirus-dieses-hausmittel-hilft-bei-leichten-symptomen-18411.html. Accessed 19 June 2020
  4. Leichter Atmen bei Lungen- und bronchialerkrankungen (2020) Corona: Pflege der Atemwege vermindert Infektionsrisiko [Corona: Care of the airways reduces the risk of infection]. [24.03.2020] https://www.leichter-atmen.de/copd-news/atemwegspflege. Accessed 19 June 2020
  5. PARI-Blog (2020) Treatment and nebuliser therapy for COVID- 19 in hospital. Interview with the Prof. Dr Kamin, Medical Director of the Hamm Lutheran Hospital. https://www.pari.com/ int/blog/treatment-and-nebuliser-therapy-for-covid-19-in-hospital-interview-with-the-prof-dr-kamin-medical-director-of- the-hamm-lutheran-hospital/. Accessed in English 27 July 2020. - Firstly accessed in German: Accessed 19 June 2020
  6. Betreut.de (2020) Coronavirus: Was Senioren & ihre Betreuer wissen müssen. [Coronavirus: What seniors and care givers need to know] www.betreut.be. Accessed 14 July 2020
  7. ETH Zurich (2020) Mit Atemwegspflege das Infektionsrisiko senken. [With airway care decrease the risk of infection.] https://ethz.ch/de/news-und- veranstaltungen/eth-news/news/2020/03/zukunftsblog-viola-vogel-mit-atemwegspflege-das-infektionsrisiko-senken.html. Accessed 14 July 2020
  8. Bronchiectasis Toolbox (2020) Hydration and humidification. https://bronchiectasis.com.au/ physiotherapy/principles-of-airway-clearance/ hydration-and-humidification. Accessed 13 July 2020
  9. Kramer A, Eggers M, Hübner N-O et al (2020) Empfehlung der DGKH. Viruzides Gurgeln und viruzider Nasenspray [Virucidal gargling and virucidal
    Nose sprays]. Deutsche Gesellschaft für Krankenhaushygiene e.V., 01.12.2020. Accessed 9 January 2021. https://www.krankenhaushygiene.de/ pdfdata/2020_12_ 02_Empfehlung-viruzides-gurgeln-nasenspray.pdf
  10. Sciensano (2020) Consensus over het rationeel en correct gebruik van mondmaskers tijdens de COVID-19-pandemie [Consensus on the rational and correct use of mouth masks during the COVID-19 pandemic]. https://covid-19.sciensano.be/sites/default/files/Covid19/consensus%20on%20the%20use%20of%20masks_ RMG_NL.pdf. Accessed 13 July 2020
  11. Sciensano (2020) Procedure voor huisartsen in geval van een mogelijk geval van COVID-19. Versie 08 juli 2020. [Procedure for doctors in the event of a possible case of COVID-19]. https:// covid-19.sciensano.be/sites/default/files/Covid19/COVID-19_ procedure_GP_NL.pdf . Accessed 13 July 2020
  12. APB (2020) Aerosoltoestellen [Aerosol devices]. Information Up date 20 March 2020 . https://www.apb.be/APB% 2 0 Documents/NL/All%20partners/CORONAVIRUS_ AEROSOL_VERHUUR_20_03_20.pdf. Accessed 19 June 2020
  13. World Health Organization (2020) Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. Scientific Brief, 29 March 2020. https://www.who.int/ publicationsdetail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations. Accessed June 19, 2020.
  14. Pfeifer M, Ewig S, Voshaar T et al (2020) Position paper for the state-of-the-art application of respiratory support in patients with COVID-19. Respiration 99:521–541. https://doi.org/10.1159/ 000509104
  15. Kimura KS, Freeman MH, Wessinger BC et al (2020) Interim analysis of an open-label randomized controlled trial evaluating nasal irrigations in non-
    hospitalized patients with COVID-19. Int Forum Allergy Rhinol Sep 11 [Epub ahead of print]. https://doi.org/10.1002/alr.22703
  16. ClinicalTrials.gov Identifier: NCT04347538. Impact of nasal sa- line irrigations on viral load in patients with COVID-19. https:// clinicaltrials.gov/ct2/ show/record/NCT04347538?term= saline&cond=covid-19&draw=2&rank=1
  17. Santos FKG, Barros Neto EL, Moura TMCPA et al (2009) Molecular behavior of ionic and nonionic surfactants in saline medium. Colloids and Surfaces A: Physicochemical and Engineering Aspects 333:156–162. https://doi.org/10.1016/j. colsurfa.2008.09.040
  18. Staszak K, WieczorekD MK (2015) Effect of sodium chloride on the surface and wetting properties of  aqueous solutions of cocamidopropyl betaine. J Surfact Deterg 18:321–328. https:// doi.org/10.1007/s11743-014-1644-8
  19. Avery ME, Mead J (1959) Surface properties in relation to atelec- tasis and hyaline membrane disease. AMA J Di Child 97(5_Part_I):517-5523. https://doi.org/10.1001/archpedi.1959. 02070010519001
  20. Ghadiali SN, Gaver DP (2008) Biomechanics of liquid-epithelium interactions in pulmonary airways. Respir Physiol Neurobiol 163(1-3):232-243. https://doi.org/10.1016/j.resp.2008.04.008
  21. Huang J, Hume AJ, Abo KM et al (2020) SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. bioRxiv [Preprint]: 175695. https://doi.org/10.1101/2020.06.30.175695
  22. Takano H (2020) Pulmonary surfactant itself must be a strong defender against SARS-CoV-2. Medical Hypotheses 144: 110020. https://doi.org/10.1016/j.mehy.2020.110020
  23. Edwards DA, Man JC, Brand P et al (2004) Inhaling to mitigate exhaled bioaerosols. Proc Natl Acad Sci USA 101(50):17383-17388. https://doi.org/10.1073/pnas.0408159101
  24. Edwards DA, Fiegel J, DeHaan W et al (2006) Novel inhalants for control and protection against airborne infections. Resp Drug Delivery 1:41-48
  25. Edwards D, Hickey A, Batycky R et al (2020) A new natural defense against airborne pathogens. QRB Discovery 1:e5. https://doi.org/10.1017/qrd.2020.9
  26. Fiegel J, Clarke R, Edwards DA (2006) Airborne infectious disease and the suppression of pulmonary bioaerosols. Drug Discov Today 11(1-2):51–57. https://doi.org/10.1016/S1359-6446(05)03687-1
  27. Simonds A, Hanak A, Chatwin M et al (2010) Evaluation of droplet dispersion during non-invasive ventilation, oxygen thera- py, nebuliser treatment and chest physiotherapy in clinical prac- tice: implications for management of pandemic influenza and other airborne infections. Health Technol Assess 14:131–172. https:// doi.org/10.3310/hta14460-02
  28. Hendley JO, Gwaltney JM (2004) Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection. J Clin Virol 30(4):326–328. https://doi.org/10.1016/j.jcv.2004.02.011
  29. Ramalingam S, Graham C, Dove J et al (2019) A pilot, open labelled randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Sci Rep 9:1015. https://doi.org/10.1038/s41598-018-37703
  30. Watanabe W, Thomas M, Clarke R et al (2007) Why inhaling salt water changes what we exhale. J Colloid Interface Sci 307:71–78.  https://doi.org/10.1016/j.jcis.2006.11.017
  31. Patel A, Longmore N, Mohanan A, Ghosh S (2019) Salt and pH- induced attractive interactions on the rheology of food protein- stabilized nanoemulsions. CS Omega 4(7):11791–11800. https:// doi.org/10.1021/acsomega.8b03360
  32. Wang Q, Li W, Hu N et al (2017) Ion concentration effect (Na+ and Cl-) on lipid vesicle formation. Colloids Surf B Biointerfaces. 155:287–293. https://doi.org/10.1016/j.colsurfb.2017.04.030 https://www.sciencedirect.com/science/article/abs/pii/S0927776517302163
  33. Liu S, Novoselac A (2014) Transport of airborne particles from an unobstructed cough jet. Aerosol Sci Technol 48(11):1183–1194. https://doi.org/10.1080/02786826.2014.968655
  34. Heyder J (2004) Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respi- ratory drug delivery. Proc Am Thorac Soc 1:315–320. https://doi. org/10.1513/pats.200409-046TA
  35. Rengasamy S, Zhuang Z, Niezgoda G et al (2018) A comparison of total inward leakage measured using sodium chloride (NaCl) and corn oil aerosol methods for air-purifying respirators. J Occup Environ Hyg 15(8):616–627. https://doi.org/10.1080/15459624.2018.1479064
  36. Negm N (2008) Solubilization characteristics of paraffin oil in different types of surfactants. Egyptian J Chem 51(1):21–29 https://www.researchgate.net/ publication/280015681_ Solubiliza-tion_characteristics_of_paraffin_oil_in_different_types_of_surfactants
  37. Baimes C (2020) Alberta researcher wins award for salt-coated mask innovation. The Canadian Press, CBC. https://www.cbc.ca/news/canada/edmonton/ alberta-researcher-award-salt-masks-covid-1.5813921. Accessed 10 January 2021
  38. Vejerano EP, Marr LC (2018) Physicochemical characteristics of evaporating respiratory fluid droplets. J R Soc Interface 15: 20170939. https://doi.org/10.1098/rsif.2017.0939
  39.  Yang W, Elankumaran S, Marr LC (2012) Relationship between humidity and Influenza A viability in droplets and implications for influenza’s easonality. PLoS ONE 7(10):e46789. https://doi.org/10.1371/journal.pone.0046789
  40. Wolf G, Koidl B, Pelzmann B (1991) [Zur Regeneration des Zilienschlages humaner Flimmerzellen] Regeneration of the ciliary beat of human ciliated ells. Laryngorhinootologie 70(10): 552–555. https://doi.org/10.1055/s-2007-998095
  41. Daviskas E, Anderson SD, Gonda I et al (1996) Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects. Eur Respir J 9(4):725–732. https://doi.org/10.1183/09031936.96.09040725
  42. Fu Y, Tong J, Meng F et al (2018) Ciliostasis of airway epithelial cells facilitates Influenza A virus infection. Vet Res 49(1):65. https://doi.org/10.1186/s13567-018-0568-0
  43. Keojampa BK, Nguyen MH, Ryan MW (2004) Effects of buff- ered saline solution on nasal mucociliary clearance and nasal air- way patency. Otolaryngol Head Neck Surg 131(5):679–682. https://doi.org/10.1016/j.otohns.2004.05.026
  44. Sood N, Bennett WD, Zeman K et al (2003) Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med 167(2):158–163. https://doi.org/10.1164/rccm.200204- 293OC
  45. Kim C-H, Song MH, Ahn YE et al (2005) Effect of hypo-, iso- and hypertonic saline irrigation on secretory mucins and morphology of cultured human nasal epithelial cells. Acta Oto-Laryngologica 125:1296–1300. https://doi.org/10.1080/00016480510012381
  46. Sumaily I, Alarifi I, Alsuwaidan R et al (2020) Impact of nasal irrigation with iodized table salt solution on mucociliary clearance: proof-of-concept randomized control trial. Am J Rhinol Allergy 34(2):276–279. https://doi.org/10.1177/1945892419892172
  47. Min YG, Lee KS, Yun JB et al (2001) Hypertonic saline decreases ciliary movement in human nasal epithelium in vitro. Otolaryngol Head Neck Surg 124(3):313–316. https://doi.org/10.1067/mhn. 2001. 113145
  48. Bencova A, Vidan J, Rozborilova E, Kocan I (2012) The impact of hypertonic saline inhalation on mucociliary clearance and nasal nitric oxide. J Physiol Pharmacol 63(3):309–313 http://www.jpp. krakow.pl/journal/archive/06_12/pdf/309_06_12_article.pdf
  49. Talbot AR, Herr TM, Parsons DS (1997) Mucociliary clearance and buffered hypertonic saline solution. Laryngoscope 107(4): 500–503. https://doi.org/10. 1097/00005537-199704000-00013
  50. Bennett WD, Wu J, Fuller F et al (2015) Duration of action of hypertonic saline on mucociliary clearance in the normal lung. J Appl Physiol 118(12):1483–1490. https://doi.org/10.1152/ japplphysiol.00404.2014
  51. Middleton PG, Pollard KA, Wheatley JR (2001) Hypertonic saline alters ion transport across the human airway epithelium. Eur Resp J 17:195–199 https://erj.ersjournals.com/content/17/2/195
  52. Jiao J, Yang J, Li J et al (2020) Hypertonic saline and seawater solutions damage sinonasal epithelial cell airliquid interface cul- tures. Int Forum Allergy Rhinol 10(1):59–68. https://doi.org/10. 1002/alr.22459
  53. Miwa M, Matsunaga M, Nakajima N et al (2007) Hypertonic saline alters electrical barrier of the airway epithelium. Otolaryngol Head Neck Surg 136(1):62–66. https://doi.org/10. 1016/j.otohns.2006.08.013
  54. Hauptman G, Ryan MW (2007) The effect of saline solutions on nasal patency and mucociliary clearance in rhinosinusitis patients. Otolaryngol Head Neck Surg 137(5):815–821. https://doi.org/10. 1016/j.otohns2007.07.034
  55. Balmes JR, Fine JM, Christian D et al (1988) Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols. Am Rev Respir Dis 138(1):35–39. https://doi.org/10.1164/ajrccm/138.1.35
  56. Makker HK, Holgate ST (1993) The contribution of neurogenic reflexes to hypertonic saline-induced bronchoconstriction in asthma. J Allergy Clin Immunol 92:82–88. https://doi.org/10.1016/0091-6749(93)90041-d
  57. Taube C, Holz O, Mücke M et al (2001) Airway response to inhaled hypertonic saline in patients with moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164:1810–1815. https://doi.org/10.1164/ajrccm.164.10. 2104024
  58. Lowry RH, Wood AM, Higenbottam TW (1988) Effects of pH and osmolarity on aerosol-induced cough in normal volunteers. Clin Sci (Lond) 74(4):373–376. https://doi.org/10.1042/cs0740373
  59. Mandelberg A, Amirav I (2010) Hypertonic saline or high volume normal saline for viral bronchiolitis: mechanisms and rationale. Paed Pulmonol 45:36–40. https://doi.org/10.1002/ppul.21185
  60. Bartoszewski R, Matalon S, Collawn JF (2017) Ion channels of the lung and their role in disease pathogenesis. Am J Physiol Lung Cell Mol Physiol
    313(5):L859–L872. https://doi.org/10.1152/ajplung.00285.2017
  61. Fahy JV, Dickey BF (2010) Airway mucus function and dysfunc- tion. N Engl J Med 2363(23):2233–2247. https://doi.org/10.1056/ NEJMra0910061
  62. Bustamante-Marin XM, Ostrowski LE (2017) Cilia and mucociliary clearance. Cold Spring Harb Perspect Biol 9(4): a028241. https://doi.org/10.1101/ cshperspect.a028241
  63.  Hollenhorst MI, Richter K, Fronius M (2011) Ion transport by pulmonary epithelia. J Biomed Biotechnol Article ID 174306, 16pages. https://doi.org/10.1155/2011/174306
  64. Iwan IH, Dziembowska I, Słonina DA (2019) Airways surface liquid and ion Transport - The mechanism maintained patency. Biom J Scie Techn Res 14(3):1-7. https://doi.org/10.26717/BJSTR.2019.14.002543 https://biomedres.us/fulltexts/BJSTR.MS.ID.002543.php
  65. Pinto JM, Jeswani S (2010) Rhinitis in the geriatric population. Allergy Asthma Clin Immunol 6(1):10. https://doi.org/10.1186/ 1710-1492-6-10
  66. Lillehoj EP, Kato K, Lu W, Kim KC (2013) Cellular and molec- ular biology of airway mucins. Int Rev Cell Mol Biol 303:139–202. https://doi.org/10.1016/B978-0-12-407697-6.00004-0
  67. Lieleg O, Vladescu I, Ribbeck K (2010) Characterization of par- ticle translocation through mucin hydrogels. Biophys J 98:1782–1789. https://doi.org/10.1016/j.bpj.2010.01.012
  68. McCullagh CM, Jamieson AM, Blackwell J, Gupta R (1995) Viscoelastic properties of human tracheobronchial mucin in aqueous solution. Biopolymers
    35(2):149–159. https://doi.org/10.1002/bip.360350203
  69. Button B, Goodell HP, Atieh E et al (2018) Roles of  mucus adhe- sion and cohesion in cough clearance. PNAS 115(49):12501–12506. https://doi.org/10.1073/pnas.1811787115
  70. Wills PJ, Hall RL, Wm C, Cole PJ (1997) Sodium chloride in- creases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucusdepleted bovine trachea. J Clin Inv 99(1):9–13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507760/pdf/990009.pdf
  71. Lin L, Chen Z, Cao Y, Sun G (2017) Normal saline solution nasal- pharyngeal irrigation improves chronic cough associated with allergic rhinitis. Am J Rhinol Allergy 31(2):96–104. https://doi.org/10.2500/ajra. 2017.31.4418
  72. Elkins MR, Bye PT (2011) Mechanisms and applications of hy- pertonic saline. J R Soc Med 104(Suppl 1):S2–S5. https://doi.org/10.1258/jrsm.2011.s11101
  73. Goralski JL, Wu D, Thelin WR et al (2018) The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J 51(5):1702652. https://doi.org/10.1183/13993003. 02652-2017
  74. Boon M, Jorissen M, Jaspers M et al (2016) The influence of nebulized drugs on nasal ciliary activity. J Aerosol Med Pulm Drug Deliv 29(4):378–385. https://doi.org/10.1089/jamp.2015. 1229
  75. Rusznak C, Devalia JL, Lozewicz S, Davies RJ (1994) The assessment of nasal mucociliary clearance and the effect of drugs. Respir Med 88(2):89-101. https://doi.org/10.1016/0954-6111(94)90020-5
  76. Workman AD, Cohen NA (2014) The effect of drugs and other compounds on the ciliary beat frequency of  human respiratory epithelium. Am J Rhinol Allergy 28(6):454-464. https://doi.org/10.2500/ajra.2014.28.4092
  77. Rivera JA (1962) Cilia, ciliated epithelium, and ciliary activity. International Series of Monographs and Applied Biology. 1st edn. Pergamon Press ltd, Oxfor-London-NewYork-Paris pp.50-58. ISBN 978008009623
  78. Paul P, Johnson P, Ramaswamy P et al (2013) The effect of ageing on nasal mucociliary clearance in women: a pilot study. Pulmonol Article ID598589:5 pages. https://doi.org/10.1155/2013/598589
  79. Purushothaman PK, Priyangha E, Vaidhyswaran R (2020) Effects of prolonged use of facemask on healthcare workers in tertiary care hospital during COVID-19 pandemic. Indian J Otolaryngol Head Neck Surg:1–7. https://doi.org/10.1007/s12070-020-02124- 0
  80. White DE, Bartley J, Nates RJ (2015) Model demonstrates func- tional purpose of the nasal cycle. BioMed Eng OnLine 14:38. https://doi.org/ 10.1186/s12938-015-0034-4
  81. Tarran R, Trout L, Donaldson SH, Boucher RC (2006) Soluble mediators, not cilia, determine airway surface liquid volume in normal and cystic fibrosis superficial airway epithelia. J Gen Physiol 127(5):591–604. https://doi.org/10.1085/jgp.200509468
  82. Hildenbrand T, Weber RK, Brehmer D (2011) Rhinitis sicca, dry nose and atrophic rhinitis: a review of the literature. Eur Arch Otorhinolaryngol 268(1):17–26. https://doi.org/10.1007/s00405- 010-1391-z
  83. Harvey PR, Tarran R, Garoff S, Myerburg MM (2011) Measurement of the airway surface liquid volume with simple light refraction microscopy. Am J Respir Cell Mol Biol 45(3): 592–599. https://doi.org/10.1165/rcmb.2010-0484OC
  84. Tanner K, Roy N, Merrill RM et al (2010) Nebulized isotonic saline versus water following a laryngeal desiccation challenge in classically trained sopranos. J Speech Language Hearing Res 53(6):1555–1566. https://doi.org/10.1044/1092-4388(2010/09-0249
  85. Personal communications by pneumologists, dentists and paedia- tricians wearing daily well-fitting professional masks, July- October 2020
  86. Slapak I, Skoupa J, Strnad P, Hornik P (2008) Efficacy of isotonic nasal wash (seawater) in the treatment and prevention of rhinitis in children. Arch Otolaryngol Head Neck Surg 134:67–74. https:// doi.org/10.1001/archoto.2007.19
  87. Newster (2020) Eco-sustainable technology for the processing of healthcare waste (HCW), on-site or in centralized treatment centers. Coronaviruses: SARS, MERS and Covid19. 28/02/2020 http:// www.newstergroup.com/news/coronavirusessars_mers_and_covid19
  88. Machado RRG, Glaser T, Araujo DB et al (2020) Hypertonic saline solution inhibits SARS-CoV-2 in vitro assay. bioRxiv 2020.08.04:235549. https://doi.org/10.1101/2020.08.04.235549
  89. Hoffmann M, Kleine-Weber H, Schroeder S et al (2020) SARS- CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2): 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052
  90. Hou Y, Zhao J, Martin W et al (2020) New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Med 18:art.No.216. https://doi.org/10.1186/s12916-020-01673-z
  91. Sungnak W, Huang N, Bécavin C et al (2020) SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 26:681–687. https://doi.org/10. 1038/s41591-020-0868-6
  92. Rushworth CA, Guy JL, Turner AJ (2008) Residues affecting the chloride regulation and substrate selectivity of the angiotensin-converting enzymes (ACE and ACE2) identified by site-directed mutagenesis. FEBS J 275(23):6033–6042. https://doi. org/10.1111/j.1742-4658.2008.06733
  93.  Guy JL, Jackson RM, Acharya KR et al (2003) Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence. Biochemistry 42(45):13185–13192. https://doi.org/10.1021/bi035268s
  94. Vincent MJ, Bergeron E, Benjannet S et al (2005) Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2:69. https://doi.org/10.1186/1743-422X-2-69
  95. Chitranshi N, Gupta VK, Rajput R et al (2020) Evolving geo- graphic diversity in SARS-CoV2 and in silico analysis of replicat- ing enzyme 3CLpro targeting repurposed drug candidates. J Transl Med 18(1):278. https://doi.org/10.1186/s12967-020- 02448-z
  96. Graziano V, McGrath WJ, DeGruccio AM et al (2006) Enzymatic activity of the SARS coronavirus main proteinase dimer. FEBS letters 580(11):2577–2583. https://doi.org/10.1016/j.febslet.2006. 04.004
  97. Ferreira JC, Rabeh WM (2020) Biochemical and Biophysical characterization of the main protease, 3-chymotrypsin-like prote- ase (3CLpro), from the novel coronavirus disease 19(COVID-19). Research Square. New York University Abu Dhabi, pp 1-17. https://assets.researchsquare.com/files/rs-40945/v1/ e41c3648-96c7-4953-bb2b-a5c5d1a19e7f.pdf
  98. Chang HP, Chou CY, Chang GG (2007) Reversible unfolding of the severe acute respiratory syndrome coronavirus main protease in guanidinium chloride. Biophys J 92(4):1374–1383. https://doi. org/10.1529/ biophysj.106.091736
  99. Abian O, Ortega-Alarcon D, Jimenez-Alesanco A et al (2020) Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int J Biol Macromol 164:1693–1703. https://doi.org/10.1016/j.ijbiomac. 2020.07.235
  100. Grum-Tokars V, Ratia K, Begaye A et al (2008) Evaluating the 3C-like protease activity of SARS-Coronavirus: recommendations for standardized assays for drug discovery. Virus Res 133(1):63-73. https://doi.org/10.1016/j.virusres.2007.02.015
  101. Shi J, Song J (2006) The catalysis of the SARS 3C-like protease is under extensive regulation by its extra domain. The FEBS Journal 273(5):1035–1045. https:// doi.org/10.1111/j.1742-4658.2006. 05130.x
  102. Bestle D, Heindl MR, Limburg H et al (2020) TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells.
    Life Sci Alliance 3(9):e202000786. https:// doi.org/10.26508/lsa.202000786
  103. Shang J, Wan Y, Luo C et al (2020) Cell entry mechanisms of SARS-CoV-2. PNAS 117(21):11727–11734. https://doi.org/10.1073/pnas.2003138117
  104. Hasan A, Paray BA, Hussain A et al (2020) A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J Biomol Struct Dyn:1-9. https:// doi.org/10.1080/ 07391102.2020.1754293 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189411/
  105. Izidoro MA, Gouvea IE, Santos JA et al (2009) Lindberg I, Juliano L (2009) A study of human furin specificity using synthetic pep- tides derived from natural substrates, and effects of potassium ions. Arch Biochem Biophys 487(2):105–114. https://doi.org/10.1016/j.abb.2009.05.013
  106. Zhou T, Tsybovsky Y, Olia AS et al (2020) A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike. bioRxiv [Preprint]
    2020.07.04.187989 https://doi.org/10.1101/ 2020.07. 04.187989
  107. Ou X, Liu Y, Lei X et al (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross- reactivity with SARS-CoV. Nat Commun 11(1):1620. https:// doi.org/10.1038/s41467-020-15562-9
  108. Smyrlaki I, Ekman M, Lentini A et al (2020) Massive and rapid COVID-19 testing is feasible by extractionfree SARS-CoV-2 RT-PCR. Nat Commun 11:4812. https://doi.org/10.1038/s41467-020-18611-5.
  109. Fischer H, Widdicombe JH (2006) Mechanisms of acid and base secretion by the airway epithelium. J Membr Biol 211(3):139-150. https://doi.org/10.1007/s00232-006-0861-0
  110. Reddi BA (2013) Why is saline so acidic (and does it really mat- ter?). Int J Med Sci 10(6):747–750. https://doi.org/10.7150/ijms. 5868
  111. Enuka Y, Hanukoglu I, Edelheit O et al (2012) Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem Cell Biol 137(3): 339–353. https://doi.org/10.1007/s00418-011-0904-1
  112.  Anand P, Puranik A, Aravamudan M et al (2020) SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. eLife 9:e58603. https://doi.org/10.7554/eLife.58603
  113.  Jaimes JA, Millet JK, Whittaker GR (2020) Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site. iScience 23:101212. https://doi.org/10.1016/j.isci.2020. 101212
  114. Ji HL, Zhao R, Matalon S, Matthay MA (2020) Elevated plas- min(ogen) as a common risk factor for COVID-19 susceptibility. Physiol Rev 100(3):1065–1075. https://doi.org/10.1152/physrev. 00013.2020
  115. Kleyman TR, Carattino MD, Hughey RP (2009) ENaC at the cutting edge: regulation of epithelial sodium channels by prote- ases. J Biol Chem 284(31):20447–20451. https://doi.org/10.1074/ jbc.R800083200
  116. Szabó GT, Kiss A, Csanádi Z, Czuriga D (2020) Hypothetical dysfunction of the epithelial sodium channel may justify neurohumoral blockade in coronavirus disease 2019. ESC Heart Fail 17. https://doi.org/10.1002/ehf2.13078
  117. Noda M, Hiyama TY (2015) The Nax Channel: What it is and what it does. The Neuroscientist 21(4):399–412. https://doi.org/ 10.1177/1073858414541009
  118. Marunaka Y, Marunaka R, Sun H et al (2016) Na+ homeostasis by epithelial Na+ channel (ENaC) and Nax channel (Nax): cooperation of ENaC and Nax. ATM 4(Suppl 1):S11. https://doi.org/10. 21037/atm.2016.10.42
  119. Blé FX, Cannet C, Collingwood S et al (2010) ENaC-mediated effects assessed by MRI in a rat model of hypertonic saline-induced lung hydration. Br J Pharmacol 160(4):1008–1015. https://doi.org/10.1111 /j.1476-5381.2010.00747.x
  120. Ramalingam S, Cai B, Wong J et al (2018) Antiviral innate im- mune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Sci Rep 8: 13630. https://doi.org/10.1038/s41598-018-31936-y
  121. Zhang N, Francis KP, Prakash A, Ansaldi D (2013) Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of nearinfrared nanoparticles. Nat Med 19(4):500–505. https://doi.org/10.1038/nm.3110
  122. Suzuki K, Yamada M, Akashi K, Fujikura T (1986) Similarity of kinetics of three types of myeloperoxidase from human leukocytes and four types from HL-60. Arch Biochem Biophysics 245(1): 167–173. https://doi.org/10.1016/0003-9861(86) 90201-8
  123. Wang G, Nauseef WM (2015) Salt, chloride, bleach, and innate host defense. J Leukocyte Biol 98(2):163–172. https://doi.org/10. 1189/jlb.4RU0315-109R
  124. Chandler JD, Day BJ (2012) Thiocyanate: a potentially useful therapeutic agent with host defense and antioxidant properties. Biochem Pharmacol 84(11):1381-1387. https://doi.org/10.1016/ j.bcp.2012. 07.029
  125. Nadesalingam A, Chen JHK, Farahvash A, Khan MA (2018) Hypertonic saline suppresses NADPH oxidasedependent neutrophil extracellular trap formation and promotes apoptosis. Front Immunol 9:359. https://doi.org/10.3389/fimmu.2018.00359.
  126. Delgado-Enciso I, Paz-Garcia J, Barajas-Saucedo CE, Mokay- Ramírez KA Meza-Robles C, Lopez-Flores R (2020) Patient- reported health outcomes after treatment of COVID-19 with neb- ulized and/or intravenous neutral electrolyzed saline combined with usual medical care versus usual medical care alone: a randomized, open-label, controlled trial. Res Sq [Preprint] 10:rs.3.rs-68403. https://doi.org/10.21203/ rs.3.rs-68403/v1
  127. WHO (2020) Saline. https://www.who.int/ emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters#saline
  128. WHO (2020) Can rinsing your nose regularly with saline solution prevent Covid-19? https://www.who. int/docs/default-source/searo/thailand/12myths- final099bfbf976c54d5fa3407a65b6d 9fa9d.pdf
  129. Salmon Ceron D, Bartier S, Hautefort C et al (2020) APHP COVID-19 research collaboration. Selfreported loss of smell without nasal obstruction to identify COVID-19. The multicenter Coranosmia cohort study. J Infect 81(4):614–620. https://doi.org/10.1016/j.jinf.2020.07.005
  130. Voshaar T. COVID-19 Therapie aus Sicht eines Aerosol-Experten. PARI.de - Artzeportal 28 Juli 2020. https://www.pari.com/de/aerzteportal/news/ covid-19-therapie-aus-sicht-eines-aerosol-experten Accessed 10 January 2021
  131. Jayaweera M, Perera H, Gunawardana B, Manatunge J (2020) Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res 188: 109819. https://doi.org/10.1016/j.envres.2020.109819
  132. WHO (2020) Transmission of SARS-CoV-2: implications for infection prevention precautions. https://www.who.int/news-room/ commentaries/detail/transmission-of-sars-cov-2-implications-for-infection-prevention-precautions Accessed 10 Jan-uary 2021
  133. Ueki H, Furusawa Y, Iwatsuki-Horimoto K et al (2020) Effectiveness of face masks in preventing airborne transmission of SARS-CoV-2. mSphere 5(5):e00637–e00620. https://doi.org/ 10.1128/ mSphere.00637-20
  134. Ehre C (2020) SARS-CoV-2 infection of airway cells. N Engl J Med 383:969. https://doi.org/10.1056/NEJMicm2023328
  135. Zhu N, Wang W, Liu Z et al (2020) Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells. Nat Commun 11:3910. https://doi.org/10.1038/s41467-020-17796-z
  136. Robinot R, Hubert M, Dias de Mehlo G et al (2020) SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. bioRxiv. https://doi.org/10.1101/2020.10.06.328369
  137. Baker AN, Richards SJ, Guy CS et al (2020) The SARS-COV-2 spike protein binds sialic acids and enables rapid detection in a lateral flow point of care diagnostic device. ACS Cent Sci 6(11): 2046–2052. https://doi.org/10.1021/acscentsci.0c00855
  138. Hou YJ, Okuda K, Edwards CE et al (2020) SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract. Cell 182(2):429–46.e14. https://doi.org/10.1016/j.cell.2020. 05.042
  139. Burke W (2014) The ionic composition of nasal fluid and its function. Health 06(08):720-728. https://doi.org/10.4236/health. 2014.68093 https://www.scirp.org/pdf/Health _2014032610554655.pdf
  140. Grandjean Lapierre S, Phelippeau M, Hakimi C et al (2017) Cystic fibrosis respiratory tract salt concentration: an exploratory cohort study. Medicine 96(47):e8423. https://doi.org/10.1097/MD.0000000000008423
  141. Kozlova I, Vanthanouvong V, Johannesson M, Roomans GM (2006) Composition of airway surface liquid determined by X- ray microanalysis. Ups J Med Sci 111(1):137-153. https://doi. org/10.3109/2000-1967-016 https://www.tandfonline.com/doi/ pdf/10.3109/2000-1967-016
  142. Matsui H, Grubb BR, Tarran R et al (1998) Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95(7): 1005–1015. https://doi.org/10.1016/s0092-8674(00)81724-9
  143. Wheatley CM, Cassuto NA, Foxx-Lupo WT et al (2010) Variability in measures of exhaled breath Na+, influence of pul- monary blood flow and salivary Na+.Clin Med Insights Circ Respir Pulm Med 4:25–34. https://doi.org/10.4137/ccrpm.s4718
  144. Song Y, Thiagarajah J, Verkman AS (2003) Sodium and chloride concentrations, pH, and depth of airway surface liquid in distal airways. J Gen Physiol 122(5):511–519. https://doi.org/10.1085/jgp.200308866
  145. Hao W, Ma B, Li Z et al (2020) Binding of the SARS-CoV-2 spike protein to glycans. bioRxiv. https://doi.org/10.1101/2020. 05.17.100537
  146. Bastier PL, Lechot A, Bordenave L et al (2015) Nasal irrigation: from empiricism to evidence-based medicine. A review. Eur Ann Otorhinolaryngol Head Neck Dis 132(5):281–285. https://doi.org/10.1016/j.anorl.2015.08.001
  147. Nimsakul S, Ruxrungtham S, Chusakul S et al (2018) Does heating up saline for nasal irrigation improve mucociliary function in chronic rhinosinusitis? Am J Rhinol Allergy 32(2):106–111. https://doi.org/10.1177/1945892418762872
  148. Niedner R (1997) Cytotoxicity and sensitization of  povidone-iodine and other frequently used antiinfective agents. Dermatology 195(Suppl2):89-92. https://doi.org/10.1159/000246038.
  149. Gudmundsdottir Á, Scheving R, Lindberg F, Stefansson B (2020) Inactivation of SARS-CoV-2 and HCoV-229E in vitro by ColdZyme® a medical device mouth spray against the common cold. J Med Virol. https://doi.org/10.1002/jmv.26554.org/10.1002/jmv.26 554.
  150. Kido H (2015) Influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options. Proc Jpn Acad Ser B Phys Biol Sci 91(8):351–368. https://doi.org/10.2183/pjab.91.351.
  151. Liu JJ, Chan GC, Hecht AS et al (2014) Nasal saline irrigation has no effect on normal olfaction: a prospective randomized trial. Int Forum Allergy Rhinol
    4(1):39-42. https://doi.org/10.1002/alr.21235.
  152. Piromchai P, Puvatanond C, Kirtsreesakul V et al (2019) Effectiveness of nasal irrigation devices: a Thai multicentre survey. PeerJ 27(7):e7000.
    https://doi.org/10.7717/peerj.7000.
  153. Navarra J, Ruiz-Ceamanos A, Moreno JJ et al (2002) Acute nasal dryness in COVID-19. medRxiv 2020.11.18.20233874 [Preprint]. https://doi.org/10.1101/2020.11.18.20233874.
 

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