Let’s talk about nasal carriage of #SARSCoV2, detection, replication, transmission. The receptor ACE2 is expressed ar high protein levels in the lower respiratory tract. There is little of the protein in the nose, mouth, upper airways. Yet it is detectable in nasal swabs, ....
...less so on oral swabs, but also in saliva, and extremely well in bronchoalveolar lavage or tracheal aspirates. This implies the virus is mainly produced in the lower lung, that’s where we see most of it. So don’t cells in the upper respiratory tract produce the virus at...
...similar quantities as the lower lung, or do they not get infected as well? Virus shedding is pretty comparable in comparable tissues - lung epithelia of the nose and larger airways, but not the lower lung, which serve as a thin gas barrier. You could anticipate...
...different shedding rates, but the vastly higher number of gas exchange cells vs airway pipework cells in the upper lung means that you have much higher particle production in the deep lung. That’s why you see more of the virus if you intubate. So if ACE2 is low in the upper...
...respiratory tract, and the surface area/number of cells vs deep lung is low, it stands to reason that you’d detect less virus. However virus load can be very low in the ‘brain stab’ nasal swabs- sometimes barely detectable. What do other viruses that infect the nose do?
They replicate like rabbits on viagra; there’s BUCKETS of virus in the nose if you have, say, flu. So if there’s not much receptor, not much infection but still production in the nose, does that mean there’s hardly enough virus there to make nasal swab RT-PCR 40% false negative?
That will happen only if you really have little amounts of virus- very little. The alternative hypothesis, the one I proposed in January, is that the virus replicated in the deep lung, but climbs out of the pipework of the lung in aerosol format: those tiny drops of water...
...that keep floating in the air after droplets have hit the floor. How much virus is in that aerosol is a good question- we are working on it. What happens to the aerosol those on its way up from the bottom of the lung though? Diffusion. We know that aerosols will...
...diffuse into wet surfaces, like the mucus in your lung pipework, nose and mouth we know this from decades of inhaling aerosol treatments and how they work. So logic has it that on its way up, the lung-generated aerosol will diffuse onto the lung and nasal mucous. That’s...
...how it reaches the nose. The way up the pipework though is increasingly less loaded with virus as the aerosols diffuse into the mucous closer to the bottom of the lung. As a result a smaller fraction of virus gets further up the respiratory tree. So if no replication...
Happens in the airways or nose, you’d get a large amount of virus in the trachea, and a smaller one further up. Sounds familiar? That’s right: the lower you reach into the lung to loom for virus, the more virus you see. Here’s another factor diluting the virus in the upper...
...respiratory tract. Mucocilliary clearance- ignoring snorting, sneezing and salivary swallowing, your lungs clear up your mucous very quickly. So the amount of virus gets reduced further. At some point, a steady state-ish is reached where the exhaled virus is faster than...
Clearance mechanisms and the viral load in the nose on account of lung aerosol diffusion builds up for you to detect it in nasal swabs. Then it peaks, the immune response kicks in, and it fades away. But does the virus replicate in the nose? To date I’ve not seen microscopy...
Confirming the virus replicating inside cells from the nose- people correct me if I’ve missed something! We can pick up virus genome. We can pick up infectious virus. But we have not seen virus replicating: we assume it, because the other two ideas are true (genomes, infectivity)
So here’s the deal. Hardly any ACE2 receptor I’m the nose/ how does it get in, apart from the olfactory (breathing) epithelia? No direct evidence of local replication. A load trajectory across the respiratory tract consistent with higher replication at the bottom of the lung...
...and the expression of receptor, and a simple mechanism, diffusion of aerosols into mucous, explaining why we see less virus in the nose, with a mucous clearance contributing factor to detect less. Occam’s razor?
Remember: we don’t go into mild #covid19 patients to check if viral load is higher down there than in the nose. The method is risky for patients and staff, but in the (serious) cases we look for invasive specimens, they are always more reliable. Once again: if you don’t look...
...for something, it doesn’t mean it’s not there. It is still unknown if miles have higher viral loads in the lower lung. So whilst I’m getting closer to confirming virus in breath, the question remains about the mild patients and sites of active replication, w/ direct evidence.
