Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways upon exposure to cough‑generated droplets and aerosol particles

Balázs G. Madas, Péter Füri, Árpád Farkas, Attila Nagy, Aladár Czitrovszky, Imre Balásházy, Gusztáv G. Schay & Alpár Horváth

Centre for Energy Research

Shortcut to the publication

• The study has been published in Scientific Reports on the last day of 2020.
• It is freely available here:
• https://www.nature.com/articles/s41598-020-79985-6
• The QR code below also leads to the paper:

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Introduction

• Early scientific response to COVID-19: focus on
• understanding the spread of the disease – epidemiology
• pathogenesis following cellular entry – physiology
• Much less attention was paid to how SARS-CoV-2 from the environment reach the receptors of the target cells in the respiratory system
• The aim of the study was to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated droplets and aerosol particles

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Methods

• Application of the Stochastic Lung Deposition Model
• Original developed by:
• Koblinger, L., Hofmann, W., 1990. Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure. Journal of Aerosol Science 21, 661–674. https://doi.org/10.1016/0021-8502(90)90121-D
• Hofmann, W., Koblinger, L., 1990. Monte Carlo modeling of aerosol deposition in human lungs. Part II: Deposition fractions and their sensitivity to parameter variations. Journal of Aerosol Science 21, 675–688. https://doi.org/10.1016/0021-8502(90)90122-E
• Continuously extended since then:
• Balásházy, I., et al., 2007. Aerosol drug delivery optimization by computational methods for the characterization of total and regional deposition of therapeutic aerosols in the respiratory system. Current Computer Aided-Drug Design 3, 13–32. https://doi.org/10.2174/157340907780058727
• Füri, P., et al., 2017. Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site. Inhalation Toxicology 29, 147–159. https://doi.org/10.1080/08958378.2017.1326990

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Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Methods

• Short description of the Stochastic Lung Deposition Model
• Particle deposition in the extrathoracic airways is computed by empirical formulae based on measurements in hollow airways casts.
• Particle deposition in the intrathoracic airways is simulated by reconstructing the path of inhaled particles in a stochastic lung structure.
• Airway lengths, diameters, branching angles and gravity angles of the airways along the path of an inhaled particle is selected randomly from distributions of these parameters obtained by statistical analysis of morphometric data.
• Particles are tracked from inhalation until they deposit or leave the airways by exhalation.
• Particles can deposit by impaction, sedimentation, and diffusion mechanisms.
• Input data of the model are
• spirometric parameters (functional residual capacity),
• inhalation parameters (inhaled volume, inhalation time, breath-hold time between inhalation and exhalation, exhalation time, breathhold after exhalation),
• and particle properties (particle density, particle size or size distribution).

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Aerosol size distribution

• Size distribution of cough-generated droplets and aerosol particles from influenza patients
• Lindsley, W.G., et al. 2012. Quantity and Size Distribution of Cough-Generated Aerosol Particles Produced by Influenza Patients During and After Illness. Journal of Occupational and Environmental Hygiene 9, 443–449. https://doi.org/10.1080/15459624.2012.684582

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Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Results: regional deposition distribution I.

• 61.8% of the inhaled mass is filtered out by the upper airways
• 5.5% deposit in the bronchial airways,
• and 8.5% in the acinar airways.

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Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Results: regional deposition distribution II.

• While 2.7 ng and 5.7 ng material coughed deposit in the large and small airways, respectively, 5.8 ng reach the peripheral airways, and deposit there.
• It may also be of interest that 2.9 ng material coughed deposits in the bronchiolus respiratorius region.

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Results: distribution over airway generations

• The most affected part of the acinar airways is the 19th and 20th airway generations:
• most of the viruses penetrating the extrathoracic airways passes 19 bifurcations before depositing.
• In the bronchial region, the highest amount deposits in the 12th airway generation.
• The acinar peak is more than three-fold higher than the bronchial one.
• The difference in deposition density is much smaller as the surface of the airways strongly increases with the generation number.

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Results: deposition distribution of viral RNA

• Viral loads in RNA copy per g range from 376 to 7.86 × 10¹⁰ with a median of 4.69 × 10⁴ in throat swab samples:
• based on Pan, Y., Zhang, D., Yang, P., Poon, L.L.M., Wang, Q., 2020. Viral load of SARS-CoV-2 in clinical samples. The Lancet Infectious Diseases 20, 411–412. https://doi.org/10.1016/S1473-3099(20)30113-4
• Considering the median value, about 2500 breathing cycles are required to result in one deposited copy of RNA in the acinar airways
• accompanied by 7.3 RNA copies depositing in the extrathoracic,
• and 0.7 RNA copy depositing in the bronchial airways.
• Considering the maximum value, 4900 copies of RNA deposit in the extrathoracic airways, and 680 copies of RNA deposit in the acinar airways from a single inhalation.
• Considering that the minimum viral load of a sample to be infectious is about 1 million RNA copy per cm³, the probability of direct acinar airway infection with SARS-CoV-2 from inhalation of cough-generated droplets and aerosol particles is very low.

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Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Discussion

• Inhalation of cough-generated particles containing SARS-CoV-2 results directly in only an upper airway infection, which then can later develop into pneumonia.
• It is in agreement with clinical observations:
• first symptoms of COVID-19 are related to upper airway infections:

e.g. dry cough, anosmia, ageusia

• clinical deterioration after around one week.
• It is in agreement with virological analysis of mild cases with very high concentrations of viral RNA in and isolated the virus itself from early throat swabs:
• active replication in the upper airways.

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Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Conclusions

• From the throat of patients with mild symptoms, viruses can be transported via respiratory system.
• Potential mechanisms include
• re-inhalation of own cough,
• aerosol and droplet generation in the throat during inhalation,
• virus transport on the surface of the bronchial airways,
• or gradual infection of neighboring cells expressing ACE2 towards the periphery.
• Compromised mucus production or transport can be a risk factor for COVID-19 pneumonia.

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways

Conclusions

• Important example for prolonged exposure is the continuous re-inhalation of own coughs of infected patients, which may contribute to the progression of the disease.
• Reducing the re-inhalation of own coughs could significantly prolong, or even block the onset of further, more severe phases of COVID-19.
• Using a tissue or cloth in order to absorb droplets and aerosol particles emitted by own coughs of infected patients before re-inhalation is highly recommended even if they are alone in quarantine.
• The one week difference between the onset of their initial mild symptoms and precipitous clinical deterioration provides a precious window for prevention of pneumonia
• by blocking or significantly reducing the transport of the virus towards the acinar airways.
• Disinfection of the mucosa of the upper airways may help to avoid or prolong the progression of the disease.

Centre for Energy Research

Deposition distribution of the new coronavirus (SARS‑CoV‑2) in the human airways