New research suggests that the gums may play a key role in the transmission of the SARS-CoV-2 virus from the mouth to the lungs, where it can cause Covid-19 lung disease.
A paper published in the Journal of Oral Medicine and Dental Research puts forward the hypothesis that the virus – having entered the body through the nose and mouth – does not then travel directly to the lungs via the airways but collects in saliva, enters the subgingival plaque biofilm, and then crosses into the blood vessels through which it travels to the arteries of the lungs.
The paper, “The COVID-19 Pathway: A proposed oral-vascular-pulmonary route of SARS-CoV-2 infection and the importance of oral healthcare measures,” notes that there is still a limited understanding of the reasons for clinical variability of Covid-19 and a lack of biomarkers to identify individuals at risk of developing Covid-19 lung disease, or those who might progress to severe disease leading to intensive-care admission, mechanical ventilation, or death.
This research follows a case-control study carried out in Qatar, published in the EFP’s Journal of Clinical Periodontology in February, which showed an association between periodontitis and worse outcomes in patients with Covid-19 compared with patients without periodontitis (see JCP study shows that periodontitis is linked to Covid-19 complications).
The new paper proposes a “novel understanding of SARS-CoV-2 transmission from the mouth to the lungs and the development of Covid-19 lung disease.” Its hypothesis is based on seven factors:
- Radiological evidence for primary vascular pathological processes in the lungs.
- An understanding of the upper respiratory tract as the initial site of infection.
- The formation of a viral reservoir in the oral cavity (and saliva).
- Potential for translocation of the virus from saliva to the gingival sulcus/periodontal pocket.
- Survival of the virus within the sub-gingival plaque biofilm, thus evading the oral mucosal immune response.
- Subsequent direct vascular delivery to the pulmonary vessels.
- A model of the biological processes associated with viral binding of the ACE2 receptor on the endothelium of pulmonary vessels and how subsequent processes correlate with the radiological features of a primary pulmonary vasculopathy.
The paper states that if this model were to be confirmed, it might help explain why some individuals develop Covid-19 lung disease and others do not. Furthermore, “it would also fundamentally change the way Covid-19 is managed, providing a new line of exploration into treatments targeted at the source of the viral reservoir, the mouth.”
In addition, the authors note, if the model proved to be correct, it would mean that simple antimicrobial oral healthcare measures could be implemented both to reduce the risk of transmission between individuals and to mitigate the risk of developing lung disease, and therefore the most severe form of Covid-19.
Commenting on the research, lead author Graham Lloyd-Jones, a consultant radiologist at Salisbury District Hospital in the UK, said: “Research suggests that the virus first infects the upper airways (nasal passage and mouth), forms a reservoir in the saliva in the mouth, then passes to the lungs – but without visibly causing inflammation of the airways. Thinking anatomically, it seems straightforward that the virus in the saliva could be leaking across the gums, into the blood vessels, and is delivered directly to the lungs, exactly to the areas we see are affected by Covid-19 lung disease on chest X-rays and computed tomography (CT) scans.”
Former EFP secretary general Iain Chapple, professor of periodontology at the University of Birmingham in the UK and one of the paper’s co-authors, said: “Given the high SARS-CoV-2 viral load in saliva, this blood-borne route of transfer to the lungs is highly plausible. The invasion of the virus into host cells relies upon three receptors – ACE2, Furin, and TMPRSS2 – all of which are expressed by the sulcular epithelium, but not by all oral tissues. There is emerging evidence for viral replication in minor saliva glands and high levels of SARS-CoV-2 in saliva (104-108 per ml), creating an environment from which the virus is highly likely to enter the biofilm. In people with periodontal inflammation, we know that microorganisms enter the bloodstream during daily function. The pathway needs to be linked up and definitively proven, but it makes sense.”
Prioritising oral healthcare
The paper concludes: “Until proven or refuted, daily oral hygiene and other measures for plaque control, together with oral healthcare should be prioritised for the general public, since these measures not only improve oral health and wellbeing but could also be potentially lifesaving in the context of the pandemic.”
It quotes EFP recommendations for good general oral healthcare (such as brushing teeth twice a day for at least two minutes with a fluoridated toothpaste and using interdental brushes) and considers the potential role of mouthwashes in the light of its hypothesis on SARS-CoV-2 transmission from mouth to lungs.
It notes that both in vitro and in vivo studies have shown that mouthwash products containing Cetylpyridinium chloride (CPC) are able to inactivate SARS-CoV-2 and that in vitro results suggest that ethyl lauroyl arginate (ELA) has a virucidal activity against the virus.
“In the context of the pandemic, it would seem logical to use mouthwash products both before and after social interactions, but clinical trials are required to answer the critical question of the potential effect of these products as a means of reducing the risk of transmission between individuals,” says the paper, adding that clinical trials are also needed to specifically address the potential for mouthwashes to mitigate the development of COVID-19 lung disease, and hence the severest form of the disease.
Commenting on the research, EFP president Lior Shapira said that it “establishes the biological plausibility of the observation that Covid-19 patients with gum disease have more severe complications than periodontally healthy individuals.” He noted that “the paper emphasises the importance of periodontal health in general, and particularly during the ongoing pandemic."
Professor Nicola West, EFP secretary general, added: “More research is needed to substantiate this theory but, in the meantime, it seems sensible to take extra care in looking after our teeth and gums, get regular check-ups, and undergo treatment when needed.”
Lloyd-Jones G, Molayem S, Pontes CC, Chapple I. The COVID-19 Pathway: A proposed oral-vascular-pulmonary route of SARS-CoV-2 infection and the importance of oral healthcare measures. J Oral Med and Dent Res. 2021;2(1)-S1.