Abstract
Background: Human infection with the SARS-CoV-2 virus has caused a pandemic characterized by a plethora of diseases, of which those affecting the internal organs and nervous system can have severe, life-threatening consequences. Among the manifestations of the disease at the viral entry site, diseases in oral mucosa adnexa are rarely reported. This case report describes a COVID-19-associated aggravating parotid gland disease. Case Report: The 47-year-old, SARS-CoV-2-positive male patient, already hospitalized and now in need of ventilation, had been referred for intensive care treatment due to increasing respiratory problems. A unilateral swelling of the cheek was noticed, the cause of which was initially a parotid gland infection. Examination ruled out mechanical causes of the parotid gland. During further treatment, the patient developed a parotid abscess, which was drained extra orally. Conclusion: The oral cavity is primarily considered as a reservoir of the pathogen. There is an increasing number of reports detailing inflammation of the major salivary glands associated with SARS-CoV-2 virus. Knowledge of this association facilitates therapeutic decisions.
Human coronavirus disease 2019 (COVID-19) is a multifaceted infectious disease on a pandemic scale, of which bronchopulmonary complications are the focus of medical interest in the acute stage being the cause of significant increase in patients requiring acute intensive care and disproportionate mortality (1-3). However, the spectrum of the disease extends far beyond acute and severe respiratory disorders (4, 5). The causal virus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oronasal orifices are the main routes to SARS-CoV-2 infection and infectious disease (6). Oral mucosa and saliva are deposit sites of the virus (6). The oropharyngeal epithelia are equipped with receptors that enable virus invasion (7). Oral tissues and saliva harbor the virus in both patients and asymptomatic carriers (8). Human-to-human transmission occurs primarily via aerosols in the air we breathe (7, 9). Virus-associated oral lesions have been observed (10-12). However, these findings are numerically small in relation to the number of infected or diseased persons and it is not clear whether they are secondary consequences of the viral load on the body allowing further pathogens to destroy oral tissues or primary lesions of the virus (11, 12). Shortly after COVID-19 was considered a pandemic, single reports of facial swelling of infected individuals were observed, which were temporally related to the infectious disease. The cause of the facial swellings was acute volume increases of the major salivary glands interpreted as sialadenitis in general. The parotid gland was preferentially affected (13-17). In general, individual glands were affected and findings were unilateral. The report intends to complement reports concerning previous experiences of COVID-19 associated salivary gland swellings.
Case Report
The 47-year-old male patient not vaccinated against SARS-CoV-2 had tested positive for SARS-CoV-2.
Three days later, he was admitted to another hospital for acute respiratory distress. Another two days later, due to poor oxygenation, the patient was transferred to the intensive care unit and started on non-invasive ventilation (NIV) therapy. Initially, NIV therapy significantly improved the oxygenation of the blood. Tocilizumab has been administered since the patient was admitted to the intensive care unit. Therapy with dexamethasone (6 mg) initiated since admission to hospital was changed to prednisone after patient’s transfer to the intensive care unit.
During intensive care, a left cheek swelling was observed just above the strap of the NIV mask. However, the time of observation of this swelling cannot be determined retrospectively. Some pus had drained from the ear during intensive care treatment. The swelling was initially thought to be due to mechanical compression of the parotid gland. The otolaryngological consultation had recommended continuation of antibiotic treatment. However, a more detailed description of this early parotid-related finding is not available. Twelve days after the initial diagnosis and 9 days after hospitalization, a calculated antibiotic therapy with piperacillin/tazobactam was initiated based on bronchoscopy aspirates (Staphylococcus aureus). One day later, intubation had become necessary to maintain sufficient ventilation (prednisolone iv 50 mg). Seventeen days after diagnosis of virus infection, the patient was transferred to the university hospital for extracorporeal membrane oxygenation (ECMO) therapy due to a further deterioration in gas exchange.
Examination of the patient after transfer to the university clinic revealed a swollen, soft cheek region of the left side, no external signs of inflammation of the skin, intact external auditory canal, and open ostium of Stenson’s duct with clear saliva spontaneously discharging. Modification of patient’s ventilation by tracheotomy with relief of facial skin from elastics to secure NIV had no effect on parotid swelling. Seven days after the patient was admitted for intensified pulmonary function support in the university clinic, the patient developed a short-term oozing hemorrhage from the external auditory canal on the left side (Figure 1D-E). The finding was considered indicative of spontaneous perforation of a parotid abscess.
The patient’s medical history describes hypothyroidism corrected by substitution and gastro-esophageal reflux disease treated with pantoprazole.
Imaging. Computed tomography (CT) 18 days after diagnosis of specific viral infection revealed parotid swelling that had spread to the entire organ (Figure 1A-C). The internal structure of the gland was patchily inhomogeneous, therefore different degrees of salivary congestion and inflammation were suspected. Necrosis could not be detected. Since the soft swelling remained unchanged and the course of local findings suggested a perforation of the auditory canal, another CT was performed 11 days later. Imaging confirmed extensive progress of swelling of the gland, fluid in the mastoid cells of both sides with preferential compaction on the affected side, and swelling of the soft tissues of the external auditory canal. Within the gland, a fluid-isointense lesion measuring a maximum of 5 cm was now visible. The salivary gland findings on CT showed a confluent process indicative of an abscess. A lesion of the skull base was excluded on CT.
Treatment. The abscess was drained through a sub-auricular skin incision (Figure 1F). The postoperative drainage tubes were removed after one week. Presently, the local findings offer a largely normal parotid region with slight induration of the skin over the incision site. Clear saliva is emptied at the oral orificium of the gland. The ECMO therapy of the patient, who continues to be tracheotomized, could be terminated after 53 days. He is still being treated as an inpatient.
Infectious agents. The SARS-CoV-2 infection was caused by the delta variant. Other viral infections were excluded. Masses of Staphylococcus aureus were detected in the parotid abscess.
Discussion
The report describes a COVID-19-affected patient with complicated parotid gland disease. In this case, the swelling was initially interpreted potentially to be caused by local constriction of Stenson’s duct during the intensive care treatment of the severely affected patient. It was assumed that the mechanical fixation of the ventilator device on the facial skin had caused a restriction of saliva excretion. The local findings were not sufficient to confirm the suspected causal link between the intensive care device and parotid disease. Rather, the local findings, medical circumstances of the parotid swelling (ventilated patient, dry open mouth), and the imaging findings make it likely to be a parotid lesion associated with viral infectious disease. The phenotype of the parotid lesion is uncharacteristic and known from other (viral) parotid gland infections (18).
The pathogenesis of the parotid swelling in this case can only be suspected. Xerostomia is a predisposing factor for parotid gland inflammation. The altered and decreased saliva production is thought to promote ascending inflammation (18). Xerostomia has been reported in COVID-19 (17, 19). Several individual reports and small case series describe SARS-CoV-2 associated salivary gland swelling (13-17). The disease affects both sexes and has been observed in all ages. According to the data available to date, the timing of salivary gland swelling is not related to specific phases of the infectious disease. However, some authors have suggested that the swelling of the salivary gland is an early sign of viral uptake (14, 15). Intracellular uptake of SARS-CoV-2 virus is facilitated by the expression of angiotensin-converting enzyme 2 (ACE2) cell receptors (7). Oral epithelia and their adnexa provide the cellular prerequisite for virus binding and transmembrane passage (20). Salivary glands can serve as reservoirs of the virus (8, 9, 21-25). It is considered certain that salivary glands of asymptomatic virus carriers contribute to the virus spread in human populations. Whether the viral organotropism of salivary glands is dependent on virus variants is unknown. Nonspecific salivary gland enhancement in 18-FDG PET/CT examined asymptomatic SARS-CoV-2 carriers was registered 2 weeks after diagnosis (26). Increased persistent salivary gland swelling is recorded after COVID-19 disease (27). These changes of the salivary glands indicate the early affection of the glands by the virus infection. Virus-associated diseases of the salivary glands are rarely reported. Autopsies of patients deceased from COVID-19 have also examined salivary gland changes. From the findings, it was concluded that the spread of SARS-CoV-2 outside the respiratory tract did not cause major pathologic changes and was even negligible relative to severe lung findings, at least in terms of fatal cases (28).
Tocilizumab is a humanized monoclonal antibody that specifically binds to the α-chain of the receptor of IL-6 and inhibits signal transduction (29). Most common side effects of tocilizumab are upper respiratory tract infections, nasopharyngitis, headache, hypertension, and increases in alanine aminotransferase (ALAT) (30). From the medical reports of the first treating hospital, it is not possible to distinguish whether the parotid swelling was observed before or after the medication. A causal relationship cannot be assessed.
Conclusion
Swelling of the major salivary glands can emerge in human SARS-CoV-2 infections. The reports to date do not allow any conclusions to be drawn about the diagnostic value of the findings in the early phase of the disease. Knowledge of the relationship between viral disease and salivary gland function facilitates treatment. Severe infectious complications of salivary glands related to SARS-CoV-2 infections so far are rarely reported.
Footnotes
Authors’ Contributions
Drafting of the report: REF, CK. Treatment of the patient, collection and checking of the data, release of the manuscript for publication: all Authors.
Conflicts of Interest
The Authors have no conflicts of interest with regard to the published report. This research received no support from private or public institutions.
- Received February 17, 2022.
- Revision received March 3, 2022.
- Accepted March 4, 2022.
- Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).