ARS-CoV-2 is the causal agent for COVID-19, and the World Health Organization classifies this virus as an airborne pathogen transmitted by asymptomatic, pre-symptomatic and symptomatic individuals through close contact via exposure to infected droplets and aerosols 1,2 . Although SARS-CoV-2 transmission can occur by activities involving the oral cavity, such as speaking, breathing, coughing, sneezing and even singing [3][4][5] , most attention has focused on the nasal-lung axis of infection 6 . Oral manifestations, such as taste loss, dry mouth and oral lesions, are evident in about half of COVID-19 cases [7][8][9] , although it remains unknown whether SARS-CoV-2 can directly infect and replicate in oral tissues, such as the salivary glands (SGs) or mucosa. This is critical because, if these are sites of early infection, they could play an important role in transmitting the virus to the lungs or the gastrointestinal tract via saliva, as has been suggested for other microbial-associated diseases, such as pneumonia 10 and inflammatory bowel diseases 11,12 (Extended Data Fig. 1a).SARS-CoV-2 uses host entry factors, such as ACE2 and TMPRSS family members (TMPRSS2 and TMPRSS4) 13,14 , and understanding the cell types that harbor these receptors is important for determining infection susceptibilities throughout the body [15][16][17] . ACE2 and TMPRSS2 expression has been reported in oral tissues 18,19 ; however, there are no comprehensive descriptions of viral entry factor expression nor direct confirmation of SARS-CoV-2 infection in oral tissues. We hypothesized that SGs and barrier epithelia of the oral cavity and oropharynx can be infected by SARS-CoV-2 and contribute to the transmission of SARS-CoV-2. To test this, we generated two human oral single-cell RNA sequencing (scRNA-seq) atlases to predict cell-specific susceptibilities to SARS-CoV-2 infection. We confirmed ACE2 and TMPRSS expression in SGs and oral mucosa epithelia. SARS-CoV-2 infection was confirmed using autopsy and outpatient samples. Saliva from asymptomatic individuals with COVID-19 demonstrated the potential for viral transmission. In a prospective clinical cohort, we found a positive correlation between salivary viral load and taste loss; we also demonstrated persistent salivary antibody responses to SARS-CoV-2 nucleocapsid and spike proteins. ResultsOral tissue atlases reveal resident immune cells and niche-specific epithelial diversity. The SGs and the barrier mucosa of the oral cavity and oropharynx are likely gateways for viral infection, replication SARS-CoV-2 infection of the oral cavity and saliva

This study investigated the effect of topical antibiotic treatment on pulp revascularization in replanted teeth. Thirty-four immature teeth were selected from three young dogs. Baseline radiographs and laser Doppler flowmetry (LDF) readings were obtained. Specimens were randomly divided into four groups: Thirty-eight teeth were extracted, kept dry for 5 min, and either (Group 1) covered with minocycline mixture (G1, n = 11), (Group 2) soaked in doxycycline (G2, n = 11), or (Group 3) soaked in saline (G3-negative control, n = 6), and replanted. Teeth in Group 4 were not extracted (positive control, n = 6). Postoperative radiographs and LDF readings were obtained for 2 months after replantation. After sacrifice, the jaws were collected and processed for light microscopy. Pre- and postreplantation LDF readings and radiographs, and histologic findings were analyzed to assess revascularization. Pulp revascularization occurred in 91% (G1), 73% (G2), and 33% (G3) of the specimens. In conclusion, minocycline facilitates pulp revascularization in replanted immature teeth after replantation.

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing datasets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection andimplicates saliva in viral transmission.

Proliferative verrucous leukoplakia and hyperplasia are irreversible clinicopathologic lesions of the oral cavity and upper respiratory tract with considerable potential for evolving into verrucous or other forms of squamous cell carcinoma. Proliferative verrucous leukoplakia is a disease of the oral cavity in which verrucous hyperplasia is a part of its developmental spectrum. Verrucous hyperplasia, at other head and neck mucosal sites, may be associated with papillomas or be a de novo lesion. Human papillomavirus, as a cofactor, plays a role in some of the lesions. In the instance of verrucous hyperplasia, the authors consider it an early form of verrucous carcinoma and recommend it be treated accordingly.

Oral research concerning diabetes mellitus has revealed a number of clinical implications. These include, among others, the need for more intense management of the diabetic patient with periodontal disease because tissue destruction may be accelerated, the need for rapid control of oral infection in these patients in order to prevent exacerbation of the existing metabolic imbalance, and the desirability of performing a screening for diabetes mellitus on all patients exhibiting asymptomatic parotid enlargement. Despite the explosion of knowledge concerning diabetes mellitus that has occurred since the discovery of insulin, its definitive etiology continues to elude the scientific community and its treatment remains in the realm of clinical management rather than in that of prevention and cure. In the past, research on diabetes has focused on the role of insulin in seeking the fundamental etiology of diabetes and its complications. With the progression of research, it has become apparent that the initiation and progression of the disease probably involve the interplay of a multiplicity of factors. Hereditary and immunologic factors, as suggested earlier, appear to be operated on by environmental factors, subsequently altering the body's metabolic milieu with widespread primary and secondary effects. Fertile areas for future oral research in diabetes mellitus will include, therefore, genetics, immunology, enzymology, and basement membrane pathology. On the cellular and molecular levels, particularly, the oral cavity and associated structures comprise a somewhat under‐investigated area in diabetes mellitus research and, thus, hold great promise for increasing our knowledge of this complex disease.