Dr Graham Lloyd-Jones Profile picture
Nov 17 21 tweets 7 min read Twitter logo Read on Twitter
Summary thread of the oral-vascular-pulmonary model of #COVID-19 lung disease, why this is important and what to do about it.

Also potentially relevant in #LongCOVID

@SpringerNature review -

1/21 bit.ly/3ME7LtC
Image
2/21
Initial viral infection of epithelial lining of the upper respiratory tract mucosa (nose and mouth) ... Image
3/21
Viral replication (copying) and reservoir formation in the mouth (saliva, gingival crevicular fluid, dental plaque, periodontal tissues, minor salivary glands) ... Image
4/21
Transfer of viral particles/elements into the gingival venous drainage facilitated by micro-ulceration of the sulcular/pocket-lining epithelium due to gingivitis or periodontitis ... Image
5/21
Intravascular passage of viral particles (or procoagulant viral elements) from the venous drainage of the mouth to the neck and chest veins (jugulars and superior vena cava) … Image
6/21
… the right side of the heart … Image
7/21
… into the pulmonary circulation via the pulmonary artery, dominantly in the highly vascularized gravity-dependent lung peripheries ... Image
8/21
Direct interaction of viral particles/elements with endothelial cells of the pulmonary microvasculature, with intravascular pro-coagulant and pro-inflammatory viral interactions ... Image
9/21
... leading to vasoconstriction, endothelial dysfunction and intravascular thrombosis/immunothrombosis
(Immunothrombosis = blood vessel inflammation with clotting within small blood vessels) ... Image
10/21
Damage to the normal capillary network in the lungs (normal blood flow and normal gas exchange) ... Image
11/21
... with vascular congestion and impaired lung perfusion leading to lung damage, dominantly in the lung peripheries, with upstream pulmonary arteriovenous (AV) shunting and dilated proximal blood vessels ... Image
12/21
This model of disease development explains the vascular characteristics and vascular distribution of disease visible radiologically...
Green arrows = dilated/damaged blood vessels
Yellow arrows = lung tissue damage
(for this fig. please see original hypothesis - link below) Image
13/21
... and it explains the dominant histological/autopsy findings of pulmonary vascular congestion with clotting in the lungs at microscopic level.

doi.org/10.1016/S1473-…
14/21
Read our full @SpringerNature review - here

👇👇👇👇👇👇👇


(Published November 3rd 2023) bit.ly/3ME7LtC
Image
15/21
Original scientific hypothesis published April 2021 is accessible here


With thanks to my co-authors @l_chapple @dentalsurgeon__ and Carla Pontes (@ dr.carlapontes on Instagram) radiologymasterclass.co.uk/documents/the_…
Image
16/21
Why is this so important?

It means that it makes sense to care for your mouth if you have #COVID

Here is the mouth care guidance we offer our #COVID-19 patients @SalisburyNHS UK. It includes provision of an antiviral mouthwash against #SARS2

salisbury.nhs.uk/coronavirus/co…
Image
17/21
Based on evidence that specific mouthwash ingredients eradicate #SARS2 in vitro and make it undetectable in the mouth for a prolonged period

See this systematic review of CPC mouthwash I wrote with Italian colleagues @DrFDamico/@MMarmiere
et al

onlinelibrary.wiley.com/doi/full/10.11…
18/21
And evidence that use of mouthwash in the setting of acute COVID-19 reduces intensive care admission and mortality!

See this research paper published in @Nature
nature.com/articles/s4159…
19/21
For a deeper dive please take a look at this presentation relating to the vascular nature of acute COVID-19 lung disease. (From November 2020)
20/21
And this presentation which expands on the connections between oral health, COVID-19 and other diseases. (From March 2022)
21/21
Here's my brief summary of how to care for the mouth

1 - Stop smoking/vaping
2 - Stop eating free sugar in all its forms (sugary/fruit drinks, cake, sweets)
3 - Learn how to brush your teeth properly
4 - Visit the dentist/hygienist preventatively (before things go wrong)

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More from @DrGrahamLJ

Sep 13
Use of a nasal spray makes sense when you know that the ACE2 receptor (cellular receptor for the #SARS2 virus) is expressed in the nose 200-700 times more intensely than in the airways of the lungs.
See this - erj.ersjournals.com/content/56/3/2…
The mouth is also a site of initial infection early in the disease course of #COVID-19.
Multiple epithelial cell types in the mouth are susceptible to infection and viral replication.
nature.com/articles/s4159…
So, it also makes sense to use a mouthwash which kills the virus in the mouth.
Specific mouthwashes have been shown to reduce length of stay in hospital in those with #COVID-19 …
Read 6 tweets
Aug 3
More on imaging in the context of #LongCOVID

A thread of summarising this key paper titled -

'Pulmonary circulation abnormalities in post-acute COVID-19 syndrome: dual-energy CT angiographic findings in 79 patients '


H/T M. Oudkerk (not on Twitter)doi.org/10.1007/s00330…
Objectives of the study

'To evaluate the frequency and pattern of pulmonary vascular abnormalities in the year following COVID-19'
Methods

Study of 79 patients remaining symptomatic >6 months after hospitalization for SARS-CoV-2 pneumonia who had been evaluated with dual-energy CT angiography

(The word 'pneumonia' here is a misleading, but it's what most researchers call it, so let's go with it.)
Read 22 tweets
May 29
Thanks for playing the anatomy game everyone

Many mentioned the skin as 1 of their 5 organs

Some mentioned the gut (intestine/bowel)

There’s another organ that bridges the skin and gut, which nobody has mentioned …
The mouth! Image
Read 9 tweets
Apr 22
Published 2 years ago...

The COVID-19 Pathway: A Proposed Oral-Vascular-Pulmonary Route Of SARS-CoV-2 Infection And The Importance Of Oral Healthcare Measures
bit.ly/36uEwar

What has changed since then?
Please see this thread ... Image
The world has caught up and #COVID-19 is now widely understood to be a vascular disease. This includes the severe acute lung disease which itself is not a respiratory 'pneumonia' but a 'vasculopathy'

See this explanation of the imaging (Nov 2020)
Prothrombotic inflammatory processes are now understood to be central to the disease. We used a first principles model of direct viral interaction with endothelial ACE2 (see this short video) but clotting processes are more complex than we describe.

Read 12 tweets
Feb 3
Important news about XXB1.5 pointing out that infection is more via the ACE2 receptor than previous Omicron variants.
But … the mouth is not mentioned as an important site of infection…. cambridgeindependent.co.uk/news/fast-spre…
A thread … 1/
2/ Minor salivary glands over the surface of the tongue, inner surface of the lips, the fauces and soft palate are highly susceptible to infection and replication. Epithelial cells in these areas express the ACE2 receptor.
nature.com/articles/s4159…
3/ The mouth can be considered a viral factory with viral entry into saliva in high quantity - 100 million per ml (equivalent to half a billion viruses in a single 5 ml teaspoon). ncbi.nlm.nih.gov/pmc/articles/P…
Read 22 tweets
Dec 16, 2022
Based on imaging of the lung disease post acute #COVID/#longCOVID there might be 2 things going on

1- fibrosis due to the acute phase lung injury
2 - endothelial damage - not related to the acute disease

The literature doesn't yet reflect the complexity but getting there ...
In those with respiratory symptoms at 3 months - on Dual Energy CT scans
- 5% have visible clots in lung arteries
- 65% have microangiopathy (disease of small blood vessels of the lungs)

ncbi.nlm.nih.gov/pmc/articles/P…
Imaging which assesses perfusion (blood supply) to the lungs is likely to be most helpful post-COVID, not conventional imaging (eg X-ray or CT - other than Dual Energy CT).

- 'such imaging should be embedded in routine post-COVID-19 follow-up pathways'

ncbi.nlm.nih.gov/pmc/articles/P…
Read 8 tweets

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