Researchers at the University of São Paulo find coronavirus in gum tissue of COVID-19 patients

Infection of periodontal tissue, not just airways, explains the high viral load found in the saliva of COVID-19 patients, this study suggests.

By Elton Alisson  |  Agência FAPESP – Researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil have detected for the first time the presence of SARS-CoV-2 in the periodontal tissue of patients who died from COVID-19.

They confirmed the presence of SARS-CoV-2 in the gums by RT-PCR testing and histopathological analysis of samples taken during autopsies performed by a minimally invasive technique on COVID-19 patients who died at Hospital das Clínicas, the hospital complex run by FM-USP.

The results of the study, which was supported by FAPESP, are published in the Journal of Oral Microbiology.

The findings indicate one of the possible sources of the novel coronavirus in the saliva of COVID-19 patients, the authors of the article note. “The presence of SARS-CoV-2 in periodontal tissue may be one of the factors that contribute to the presence of this virus in the saliva of infected patients, showing that the airways aren’t necessarily the only origin of the viruses found in droplets of saliva,” Bruno Fernandes Matuck, first author of the article, told Agência FAPESP.

Only a few viruses have previously been detected in gum tissue, such as herpes simplex virus (HSV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV). Possible sources of infection include gingival epithelial cells exposed to the oral cavity and viral migration via the bloodstream.

In light of the high infectiousness of SARS-CoV-2 compared with other respiratory viruses, the researchers raised the hypothesis that periodontal pockets could be a favorable environment for viral replication, from which the virus could migrate to the saliva via periodontal tissue.

To test the hypothesis, they focused on saliva glands, periodontal tissue, and upper airway cells. “We analyzed these three oral cavity components to see if we could find out why the viral load was so high in saliva from COVID-19 patients,” Matuck said.

The researchers used a video endoscope system coupled to a smartphone to locate the first superior molar and sample the interdental papilla, using special surgical forceps, in seven deceased COVID-19 patients with an average age of 47.

Analysis of the samples showed that SARS-CoV-2 was present in the periodontal tissue of five out of the seven deceased patients as much as 24 days after the first symptoms of infection appeared in some cases.

“Based on these findings, we can say that periodontal tissue appears to be a target for SARS-CoV-2, and can contribute to the presence of the virus in saliva for a long time,” Matuck said.

Periodontal tissue infection by SARS-CoV-2 and its presence in saliva for a long time does not mean that particles of viral RNA are contagious for the entire period. “Other studies have shown that its contagiousness declines over time, after peaking about two weeks post-infection,” said Luiz Fernando Ferraz da Silva (https://bv.fapesp.br/en/pesquisador/178184/luiz-fernando-ferraz-da-silva), a professor at FM-USP and last author of the article on the study.

Periodontitis and COVID-19

Detection of SARS-CoV-2 in the gums also corroborates the hypothesis that periodontal inflammation increases the risk of developing severe COVID-19, according to the researchers, because periodontitis boosts secretion of gingival fluid into the saliva. In addition, co-morbidities such as diabetes, high blood pressure, cardiovascular disease and metabolic syndrome, all of which can make COVID-19 worse, correlate closely with the presence of periodontitis. 

“Infection of periodontal tissue by SARS-CoV-2 increases the secretion of gingival crevicular fluid and hence increases viral load in the saliva,” Matuck said.

The study also confirms the accuracy of saliva-based diagnostic testing for SARS-CoV-2, such as the method developed in Brazil by the Human Genome and Stem Cell Research Center (HUG-CELL), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP (read more at: agencia.fapesp.br/34135/). 

“RT-PCR testing is important because it detects the virus in nasopharyngeal secretions, but SARS-CoV-2 can also be detected very accurately in saliva because viral load remains high there in infected patients,” Silva said.

The researchers are now investigating viral load in the periodontal tissue of people with COVID-19 who are asymptomatic or have mild symptoms of the disease, in order to find out whether the response in these cells is different from that of severe COVID-19 patients. They are currently studying the oral cavity receptors used by SARS-CoV-2 to invade the cells.

Scientists know infection of the oral cavity by SARS-CoV-2 can have different origins. The virus infects cells via angiotensin-converting enzyme receptor 2 (ACE2). This receptor can be found in various parts of the cavity, such as the tongue, salivary gland ductal epithelial cells, and periodontal tissue. It has also been found expressed in human gingival and periodontal ligament fibroblasts.

“We’re trying to identify these receptors in periodontal tissue, taste buds and saliva glands in order to understand how viral entry into the oral cavity occurs and find out whether this is linked to loss of taste, one of the main symptoms of COVID-19,” Matuck said.

The Journal of Oral Microbiology article “Periodontal tissues are targets for SARS-Cov-2: a post-mortem study” (doi: 10.1080/20002297.2020.1848135) by Bruno Fernandes Matuck, Marisa Dolhnikoff, Gilvan V. A. Maia, Daniel Isaac Sendyk, Amanda Zarpellon, Sara Costa Gomes, Amaro Nunes Duarte-Neto, João Renato Rebello Pinho, Michele Soares Gomes-Gouvêa, Suzana C.O. M. Sousa, Thais Mauad, Paulo Hilário do Nascimento Saldiva, Paulo H. Braz-Silva and Luiz Fernando Ferraz can be read at: www.tandfonline.com/doi/full/10.1080/20002297.2020.1848135.