Frequent and Persistent Salivary Gland Ectasia and Oral Disease After COVID-19

Abstract

The clinical picture of coronavirus disease 2019 (COVID-19) in various target organs has been extensively studied and described. However, relatively little is known about the characteristics of oral cavity involvement. This is surprising, considering that oral mucosal and salivary gland cells are known targets for the direct replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that the presence of the virus in saliva is a source of transmission of the infection. The aim of our study was to investigate the presence and prevalence of oral manifestations in COVID-19 survivors. We profiled the oral involvement in 122 COVID-19 survivors that were hospitalized and followed up at a single-referral university hospital in Milan, Italy, between July 23, 2020 and September 7, 2020, after a median (interquartile range) time from hospital discharge of 104 (95 to 132) d. We found that oral manifestations, specifically salivary gland ectasia, were unexpectedly common, with oral manifestations being detected in 83.9% while salivary gland ectasia in 43% of COVID-19 survivors. Salivary gland ectasia reflected the hyperinflammatory response to SARS-CoV-2, as demonstrated by the significant relationship with C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at hospital admission, and with the use of antibiotics during acute disease. Both LDH levels and antibiotic administration survived as independent predictors of salivary gland ectasia at multivariable analysis. Temporomandibular joint abnormalities, facial pain, and masticatory muscle weakness were also common. Overall, this retrospective and prospective cohort study of COVID-19 survivors revealed that residual damage of the oral cavity persists in the vast majority of patients far beyond clinical recovery, and suggests that the oral cavity represents a preferential target for SARS-CoV-2 infection. Further studies are needed to clarify the connection between SARS-CoV-2 infection and oral disorders.

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19

“…Three studies excluded patients who were unable or unwilling to receive a magnetic resonance imaging scan. 27 , 35 , 37 Fourteen studies 8 , 14 , 16 , 19 , 23 , 25 , 27 , 29 , 32 , 35 , 37 , 38 , 44 , 45 did not report reasons for nonparticipation and/or the corresponding number of individuals excluded (eTable 4 in the Supplement ).…”

“…Among 9751 total participants, 5266 (54.0%) were male; 30 studies 9 , 10 , 11 , 12 , 13 , 15 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 33 , 34 , 35 , 36 , 37 , 40 , 41 , 42 , 44 , 45 , 46 , 47 , 48 , 51 , 52 reported mean or median ages younger than 60 years, and 14 studies 9 , 11 , 12 , 13 , 24 , 26 , 27 , 33 , 34 , 35 , 36 , 45 , 46 , 52 reported mean or median ages of 50 years or younger ( Table 1 ). Twenty-four studies 9 , 11 , 12 , 13 , 15 , 19 , 20 , 22 , 23 , 24 , 26 ,…”

“…Twenty-four studies 9 , 11 , 12 , 13 , 15 , 19 , 20 , 22 , 23 , 24 , 26 , 27 , 28 , 31 , 34 , 35 , 36 , 40 , 41 , 43 , 48 , 49 , 51 , 52 reported the baseline severity of COVID-19 illness, which varied substantially, even among hospitalized patients. Of those, 19 studies 9 , 11 , 12 , 15 , 19 , 22 , 23 , 26 , 27 , 28 , 31 , 34 , 35 , 36 , 40 , 41 , 48 , 51 , 52 included patients with 2 or more symptom severity levels (asymptomatic, mild to moderate, severe, or critical). In the remaining 5 studies, all patients had mild to moderate (n = 2), 13 , 24 severe (n = 1), 49 or critical (n = 2) 20 , 43 symptom severity.…”

“…Time zero definitions and lengths of follow-up varied substantially across studies, with very few studies using identical approaches to defining time zero, follow-up, and reporting. Time zero was defined as diagnosis or symptom onset in 16 studies, 10 , 11 , 22 , 24 , 27 , 31 , 33 , 35 , 37 , 39 , 40 , 41 , 45 , 47 , 48 , 50 hospital admission in 4 studies, 9 , 18 , 25 , 46 hospital discharge in 23 studies, 12 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 23 , 26 , 28 , 29 , 30 , 32 , 36 , 38 , 42 , 43 , 45 , 48 , 49 , 51 , 52 and recovery from acute illness in 4 studies. 8 , 13 , 34 , 44 Two studies used different time zero definitions for outpatients vs inpatients within the same study.…”

“…Data extracted included study and patient characteristics, selection criteria, length of follow-up, and outcome measurements ( Table 1 ). 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 We used 6 quality criteria based on the National Institutes of Health Quality Assessment Tool for Observational and Cohort Studies 53 to assess study design or features most likely to bias frequency estimates. Criteria comprised (1) prospective cohort (score range of 0-1, with 0 indicating no and 1 indicating yes), (2) representativeness (score range of 0-1, with 0 indicating sampling strategy unclear or nonconsecutive enrollees and 1 indicating patients were randomly selected or all eligible patients were included), (3) baseline severity of illness reported (score range of 0-1, with 0 indicating not reported and 1 indicating reported), (4) attrition (score range of 0-3, with 0 indicating not reported or attrition ≥30%, 1 indicating attrition of 20%-29%, 2 indicating attrition of 10%-19%, and 3 indicating attrition <10%), (5) repeated outcome measureme...…”