Thread by @medmastery

THREAD: (1) A thought-provoking study by @Baric_Lab using reverse genetics and autopsy specimens demonstrates nasal ACE2 binding greater than in respiratory tract.

cell.com/cell/fulltext/…

#covid19 #coronavirus

(2) The nose contained highest percentage of ACE2 expressing cells. ACE2 levels waned in more distal bronchiolar & alveolar regions.

(3) ACE2 expression patterns were paralleled by high SARS-CoV-2 infectivity of nasal epithelium with marked reduction in distal lung (bronchioles & alveoli).

(4) Certain respiratory cells high in ACE2 (and TMPRSS2) could not be infected with virus, which suggests that ACE2 expression does not tell/explain the whole infectivity story.

(5) Aerosol and fomite deposition modeling suggests that aerosol containing virus achieve highest density of deposition in the nose. The high ACE2 expression in nasal cells and high infectivity of nasal cells suggests that nose is most fertile ground for initial infection.

(6) So how does virus get into the lungs? According to the authors, given the low levels of ACE2 expression in and poor infectivity of alveolar cells, the aerosol route is questionable.

(7) Paper claims that the oral-lung aspiration axis is more likely path for secondary infection of lung following intitial nasal infection. Here‘s how that‘s supposed to work…

(8) Nasal secretions are swept by mucocilliary clearance into the oral cavity and mixed with other fluid. At night fluid is aspirated into the lungs. Aspiration is also more consistent with patchy, bibasilar infiltrates observed on CT in #covid19.

(9) Microaspiration and gastro-esophageal aspiration are observed frequently in older, diabetic, or obese subjects who are also at higher risk of severe #covid19 disease.

(10) The paper‘s autopsy studies demonstrated pathchy segmental/subsegmental disease, consistent with aspiration of virus into the lung from the oropharynx.

(11) Nasal seeding of lower lung by aspirations have also been shown by other authors: in ferret model virus delivered to nasal cavity was more efficient in causing lower lung disease than virus delivered directly into lungs.

pubmed.ncbi.nlm.nih.gov/32034144/

(12) What does this mean for our assessment of the importance of aerosols for the transmission of #SARS_CoV_2? Would be interesting to hear the thoughts of aerosol experts like @Don_Milton or @linseymarr

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