The new coronavirus epidemic is thought to have begun in Wuhan, China, in late December 2019, and there were 152,977,490 cases globally, according to John Hopkins University as of this writing.1 COVID‑19 was recognized as a pandemic by the World Health Organization (WHO) in March 2020. In the time since the identification of the COVID‑19 pandemic, the heterogeneity of COVID‑19 disease presentation and the influences of host factors have proved baffling to many in the medical community and have focused attention on comorbidities that may influence COVID‑19 presentation.

Why do oral health care professionals need to understand this virus so completely? One reason is that a first-ever study shows the oral cavity is a robust site for infection and for sources of transmission of COVID‑19.2 As well, the influences of pro-inflammatory oral conditions on COVID‑19 disease severity are of importance. A research team found that the coronavirus has an affinity for binding to cell-membrane receptors that are highly expressed in salivary gland tissues.2 This allows the virus to replicate, and in some cases, may allow for prolonged disease when infected saliva is swallowed into the gastrointestinal tract or aspirated to the lungs where it can lead to pneumonia. Based on angiotensin converting enzyme 2 (ACE2) expression and evaluation of cadaver tissue, the most likely sites of infection in the mouth are the salivary glands, tongue, and tonsils. The amount of virus in a patient’s saliva was positively correlated with taste and smell changes.2 Additionally, other research has demonstrated that SARS‑CoV‑2, the causative pathogen for of coronavirus disease 2019 (COVID‑19), suppresses the expression and function of ACE2 and induces the expression of interferon-stimulated genes at the initial phase of infection.2 SARS‑CoV‑2 uses the ACE2 receptor to facilitate viral entry into target cells, including oral mucosal epithelium.3

While much of COVID‑19 research has centered on the upper respiratory tract, including the nasopharynx, nose and lungs, the Huang study is the first to identify the mouth as a primary site for coronavirus infection and highlights the significance of wearing a face covering and physical distancing to reduce viral transmission.2 There were other studies identifying high ACE2 expression in salivary glands and discussing high affinity for SARS-COV virus in the SARS pandemic.4-6 Collaborative efforts led by the Human Cell Atlas (HCA) utilized single cell RNA sequencing (scRNAseq) datasets from across the body to examine cell-specific SARS‑CoV‑2 tropism, leading to the COVID‑19 Cell Atlas.7 Tropism is defined as a growth response in a organism that lacks the ability to move, caused by an external stimulus.8

Recent evidence suggests a relevant role of the oral cavity in the transmission and pathogenicity of SARS‑CoV‑2. We now know that SARS-CoV-2 can infect and replicate in the oral mucosa or glands.9-11 This is critical because if the glands or mucosa are sites of early infection, they may play an important and underappreciated role in transmitting virus intramucosally to the lungs or gastrointestinal tract.2 Alternatively, saliva may also play a role in transmitting the virus extraorally from asymptomatic, pre-symptomatic, or symptomatic individuals.

The human oral cavity is a diverse collection of tissue niches with potentially unique vulnerabilities to viral infection.2 These sites include oral mucosae (hard palate, buccal mucosa, dorsal and ventral tongue) as well as the terminally differentiated secretory epithelia of the minor saliva glands (distributed in the buccal and labial mucosa, hard and soft palate, ventral, and dorsal tongue) and major saliva glands (parotid, submandibular, and sublingual). Nearby are diverse oropharyngeal niches (palatine and lingual tonsils, soft palate). Saliva, a mixture of fluids, electrolytes, proteins, and cells (immune and sloughed mucosal epithelial cells) is made primarily by the saliva glands and empties into the oral cavity where it mixes with other fluids (crevicular fluid) and cells.