Covid-19: coronavirus infects and replicates in salivary glands

The virus responsible for covid-19 (SARS-CoV-2) infects and replicates in salivary gland cells. The discovery was made by researchers from the Faculty of Medicine of USP (FMUSP), with support from the Foundation for Research Support of the State of São Paulo (Fapesp), and recently published in Journal of Pathology. The study helps to explain to the world why the new coronavirus is found in large quantities in human saliva.

Salivary glands have a receptor that binds to the new coronavirus.Source:  Freepik

Salivary glands in the sights of scientists

The USP team analyzed samples of three types of salivary glands — parotid, submandibular and minor — obtained during the autopsy of patients who died from complications of covid-19 at the Hospital das Clínicas at FMUSP. Biopsies were taken in 24 patients with a mean age of 53 years, in which the team found that tissues specialized in saliva production serve as reservoirs for the new coronavirus.

Electron microscopy image shows the new coronavirus inside the salivary glands.Electron microscopy image shows the new coronavirus inside the salivary glands.Source:  Bruno Matuck/USP/Reproduction

The report is the first on a respiratory virus capable of infecting and replicating in salivary glands. Only viruses causing very high prevalence diseases, such as herpes, were believed to use the salivary glands as a reservoir. Bruno Fernandes Matuck, doctoral candidate at the Faculty of Dentistry (FO) of USP and first author of the study, said in an interview to FAPESP News Agency, that this may help explain why SARS-CoV-2 is so infectious.

A previous study had demonstrated the presence of covid-19 virus RNA in the periodontal tissue of patients who died from the disease. Due to its high infectivity, the team hypothesized that the new coronavirus could infect and replicate in salivary gland cells — without contact with nasal and lung secretions.

International studies had already shown that the salivary duct has the ACE-2 receptor — to which the spike protein of SARS-CoV-2 binds. Later, other scientists observed in animal studies that, in addition to ACE-2, other receptors present in salivary gland tissues are targets of the new coronavirus. Then, the hypothesis was tested in humans: molecular analysis (RT-PCR) of the samples indicated the presence of the virus in more than two thirds of them.

The researchers tagged a molecule with a dye that binds to the virus and receptors. So they observed the virus in situ — inside the fabrics. Then, using electron microscopy, they detected that the virus was replicating in them. “We saw several viruses clustered in the cells of the salivary glands — an indication that they are replicating inside them. They weren’t present in these cells passively,” said Matuck.

How do we get infected with covid-19?

As the mouth has a larger contact area than the nasal cavity — today identified as the main entry point for the virus — the hypothesis that the group will now analyze is whether it can be a direct entry point for SARS-CoV -two. The hypothesis is quite plausible, since virus receptors are found in various parts of the organ, such as the gums and mucous membranes.

The group is going to map these receptors and quantify the replications in tissues in partnership with researchers from the University of North Carolina, in the United States, as explained by Luiz Fernando Ferraz da Silva, a professor at FMUSP and project coordinator. “It could be that the mouth is a viable means of direct entry of the virus,” reinforced Matuck.

The study should also see if older people have more ACE-2 receptors in their mouths compared to younger people, although even in those patients with less salivary tissue, the study found a high viral load. Matuck explained that even with almost no salivary tissue, with a lot of fatty tissue present, these patients still had a relatively high viral load.

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