COVID-19: SARS-CoV-2 Aerosol Mechanisms

Aerosol Exposure

Physical transport (droplets) and aerosol inhalation

Covid-19 is respiratory infection caused by the SARS-CoV-2 virus, which can affect the upper and lower respiratory tract. SARS-CoV-2 is an opportunistic airborne pathogen that infects cells expressing the ACE-2 enzyme, the host cell receptor for viral entry. Airborne respiratory infections may be transmitted by direct inhalation into the respiratory tract, or introduced into the oro/naso-pharynx by hand, or following ocular exposure and transmission through tear ducts. Neither the relative importance of, nor the minimum infectious dose of SARS-CoV-2 virus for the different pathways of infection transmission are known.

High level of certainty:

  1. Host cell receptors for viral infection in the respiratory tract: The ACE-2 receptor necessary for SARS-CoV-2 cell entry has been reported to display an ‘infection gradient’ where a decrease in the permissiveness of airways cells to SARS-CoV-2 was associated with a decreasing density of ACE-2 expression in the lower, compared to the upper respiratory tract1. However, ACE-2, which is the host receptor for SARS-CoV-1 was shown to have higher expression in alveolar cells than bronchial cells2.
  2. Evidence for airborne disease transmission: SARS-CoV-2 nucleic acid has been detected in large respiratory droplets, in small aerosol particles/droplets, and on a variety of surfaces on settings where disease transmission occurred3,4.
  3. Risk assessment of viral inhalation: SARS-CoV-2 aerosols spanning the droplet-to-particle continuum have been reported to possess an aerodynamic size distribution which would be suitable for deposition within the thoracic airways (0.25-10 μm)5,6. Aerosol of this size distribution have a low nasal deposition fraction under conditions of quiet breathing, and SARS-CoV-2 aerosols were infectious in cell culture 7, although the latter report has not been fully peer-reviewed.
  4. Presence of virus in the respiratory tract: Patients with pulmonary symptoms of SARS-CoV-2 infection have been reported to return higher positivity rates for respiratory samples (e.g. broncheoalveolar lavage), including when oro/naso-pharyngeal swabs returned negative results8,9. However, the number of respiratory samples taken was lower than upper airway swabs, and patients may have been swabbed after nasal shedding rates had peaked.

Low level of certainty:

  1. The dose of SARS-CoV-2 virus required to cause infection: The minimum infectious dose (MID) for SARS-CoV-2 is not yet known, however the MID for SARS-CoV-1 was relatively low in the range 1-280 virions11.
  2. The relative importance of upper and lower airways infection: SARS-CoV-2 exhibited a dose-dependent severity of infection in animal models and aerosolized virus produced more severe clinical symptoms than intranasal administration12. This study has not been peer reviewed, and it is unknown whether the restriction to asymptomatic or mild symptomatic transmission in humans is due to virus depositing solely in the nasal cavity.
  3. airflow turbulence in the respiratory tract interacting with fluids lining the walls of the airways12;
  4. The establishment of respiratory tract infection: Disease transmission in superspreading events has been linked to airborne aerosol transmission4. However, it is unclear whether SARS-CoV-2 infection is established directly in the lower airways, or whether infection occurs in the upper respiratory tract, and is transmitted to the lower airways by aspiration.

References:

  1. Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH, et al. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020; 182(2):429-446.
  2. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Rapid Communication Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol J Pathol. 2004 203(2):631–7.
  3. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 382(16):1564–7.
  4. Miller SL, Nazaroff WW, Jimenez JL, Boerstra A, Buonanno G, Dancer SJ, et al. Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event. Indoor Air. 2020; Early View ahead of print; https://doi.org/10.1111/ina.12751
  5. Liu Y, Ning Z, Chen Y, Guo M, Liu Y, Kumar Gali N, et al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020;582.
  6. Leung NHL, Chu DKW, Shiu EYC, Chan KH, McDevitt JJ, Hau BJP, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 26(5):676–80.
  7. Santarpia JL, Herrera VL, Rivera DN, Ratnesar-Shumate S, Reid SP, Denton PW, et al. The Infectious Nature of Patient-Generated SARS-CoV-2 Aerosol. Not yet peer-reviewed, Available from: https://doi.org/10.1101/2020.07.13.20041632
  8. Liu R, Han H, Liu F, Lv Z, Wu K, Liu Y, et al. Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta. 2020; 505:172–5.
  9. Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: Retrospective cohort study. BMJ 2020; 369:m1443.
  10. Hui KPY, Cheung M-C, Perera RAPM, Ng K-C, Bui CHT, Ho JCW, et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med. 2020 8(7):687–95.
  11. Watanabe T, Bartrand TA, Weir MH, Omura T, Haas CN. Development of a dose-response model for SARS coronavirus. Risk Anal. 2010 30(7):1129–38.
  12. Johnston SC, Jay A, Raymond JL, Rossi F, Zeng X, Scruggs J, et al. Development of a Coronavirus Disease 2019 Nonhuman Primate Model Using Airborne Exposure. Not yet peer-reviwed, available from: http://biorxiv.org/content/early/2020/06/26/2020.06.26.174128.abstract

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