key: cord-1017039-a4kvkyx8
authors: Lamberghini, Flavia; Trifan, Gabriela; Testai, Fernando D.
title: SARS-CoV-2 Infection in Asymptomatic Pediatric Dental Patients
date: 2021-01-19
journal: J Am Dent Assoc
DOI: 10.1016/j.adaj.2021.01.006
sha: bff03e76868dc7ed0a11a3081b8aedcf337508e0
doc_id: 1017039
cord_uid: a4kvkyx8

Background Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are typically asymptomatic but contagious. Here we investigated the positivity rate of asymptomatic SARS-CoV-2 infection in pediatric dental patients.background Methods We reviewed consecutive charts of children aged <18 scheduled for elective dental procedures between 04/01/20 and 08/01/20. All patients were screened for signs and symptoms of SARS-Cov-2 infection. Asymptomatic patients scheduled for dental procedures underwent polymerase-chain reaction (PCR) testing for SARS-CoV-2. Sociodemographic characteristics were abstracted and positivity rates calculated. Variables for (+) SARS-CoV-2 and (-) SARS-CoV-2 individuals were compared using Fisher’s exact and Mann-Whitney U tests. Results The sample size was 921. The median age was 6 and 50.9% were males. The overall SARS-CoV-2 positivity rate was 2.3%. Age, insurance status, past medical history, and dental diagnosis were comparable in SARS-CoV-2 positive and negative patients. Positivity rates were statistically higher for Hispanics/Latinx compared to other groups (p= 0.038).results Conclusion Though the yield of testing is low, the systematic evaluation of asymptomatic pediatric dental cases by PCR results in the identification of SARS-CoV-2 carriers who could be infectious. In our study, Hispanics/Latinx had a higher positivity rate than other demographic groups.conclusion Practical Implications PCR testing for SARS-CoV-2 of asymptomatic patients in pediatric dentistry adds value to the use of screening questionnaires for the identification of infected individuals who could be contagious.

The coronavirus disease 2019 (COVID-19) pandemic continues to spread, with almost 54 million confirmed cases worldwide and more than 11 million people in the United States (US) as of November 20, 2020 (1) . Chicago, one of the hotspots in the US, has approximately 573,000 reported cases (2) .

COVID-19 is a disease caused by the zoonotic pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This presents with non-specific flu-like symptoms and its most common clinical complication is acute respiratory distress syndrome, which is the leading cause of death (3) .

Since severe illness due to SARS-CoV-2 in children is rare, screening efforts have targeted largely adult populations (4, 5) . Thus, the epidemiology of SARS-CoV-2 infection in children is not well known and rapidly evolving. Children comprise approximately 20% of the United States (US) population (6) .

However, based on data of the US Centers for Disease Control and Prevention (CDC), SARS-CoV-2 cases occur in only 1.7% of the individuals aged <4 and 7.7% of those aged 5-17 (7) . Patients that require medical care may have comorbid conditions that can predispose them to SARS-CoV2 infection (8) . Rates between 0.6% and 13.7% were reported in asymptomatic cohorts (9) (10) (11) (12) (13) . Most of these studies included adults only. Three studies that tested asymptomatic surgical and oncologic pediatric patients by PCR reported positivity rates for SARS-CoV-2 between 0.6% and 2.5% (9) (10) (11) . Also, a study including 33,041 asymptomatic children tested in different US hospitals reported a pooled prevalence of 0.7% (14) .

Although children typically have a benign course than adults or remain asymptomatic, they have the potential to carry significant viral loads and be a source of infection (15) . SARS-Cov-2 is present in high concentrations in the oral cavity and the pharynx (16) . In addition, dental procedures can generate aerosols that increase the risk of contagion (17) . Thus, dental healthcare providers are at high risk of getting infected if they encounter a positive SARS-CoV-2 patient. In the COVID-19 pandemic, the CDC and the American Dental Association (ADA) released interim guidelines for infection control in dental practices (16, 18) . These include screening of every patient for signs and symptoms of COVID-19, the use universal personal protection equipment (PPE) and source control J o u r n a l P r e -p r o o f strategies, such as use of facemask at all times, frequent hand hygiene, standard sequence of donning and doffing, and the implementation of technical approaches to reduce disease transmission. More recently, the CDC suggested SARS-CoV-2 testing for asymptomatic dental patients undergoing dental care as a way to identify carriers and reduce the risk for exposures in dental facilities (16) . This new strategy, however, has not been universally adopted.

The identification of patients with SARS-CoV-2 is important to guide the implementation of infection control strategies and mitigate the risk of infection of dental healthcare providers. Despite these benefits, the epidemiology of SARS-CoV-2 infection in asymptomatic children requiring dental procedures has not been investigated. Here, we report the positivity rate of SARS-CoV-2 infection in asymptomatic children attending a high-volume pediatric dental practice in Chicago, Illinois.

This retrospective study was conducted in a high-volume pediatric dental clinic associated with the University of Illinois at Chicago. The study was reviewed and approved by the local Institutional Review Board (IRB). Due to the nature of the study, the IRB waived the need for consent. The cohort analyzed comprised children <18 years who were scheduled for (A) comprehensive dental care under general anesthesia, or (B) routine dental care that required aerosol-generating procedures. Data collection of consecutive cases began in May 1, 2020 and ended in August 1, 2020. As part of our standard practice, all patients underwent preoperative telephone screening for signs and symptoms of COVID-19 or exposure to either proven or suspected cases of SARS-CoV-2, as recommended by the CDC (19) . Table   1 depicts a copy of the screening questionnaire. Patients who confirmed having signs and symptoms of COVID-19 or exposure to either proven or suspected cases of SARS-CoV-2 during the preoperative screening were referred to their primary care physician for further evaluation and were not part of this study. SARS-CoV-2 testing was performed in all patients that answered "no" to all the screening questions. Nasopharyngeal swabs were obtained by clinic personnel that received education on specimen collection and handling as recommended by the CDC (20). Samples were analyzed for SARS-J o u r n a l P r e -p r o o f Cov-2 RNA by reverse transcription PCR at Simple Laboratories (Chicago, IL) (limit of detection of 10 RNA copies per μl; specificity >99%) (21). Parents or legal guardian of children with positive PCR testing were informed of the results and referred for pediatric evaluation.

Demographics (age, gender, and race/ethnicity), insurance type, dental diagnosis and past-medical history were abstracted from the electronic dental record. In addition, for the Hispanic/Latinx patients, we extracted language of preference of the parent or caregiver as a measure of acculturation (22) . Results are presented as median and interquartile ranges (IQR), total number (n), percentage (%) and relative risk (RR) with 95% confidence interval (95% CI). Age distribution was analyzed using Kolmogorov-Smirnov Test. Positivity rates were calculated as number of positive SARS-CoV-2 cases divided by the total number of cases tested for each group. The characteristics of SARS-Cov-2 positive and negative patients were compared using Fisher's exact test for categorical variables and Mann-Whitney U test for continuous variables. All tests of significance were 2-tailed, with a threshold for significance of p<0.05.

Statistical analyses were done using SPSS version 27 (SPSS Inc, Chicago, IL).

In an exploratory analysis, we investigated the effect of sex on positivity rate. To this end, we pooled data from independent studies that reported positivity rates in asymptomatic pediatric cohorts (9, 10). The meta-analysis was performed using RevMan Version 5.4 (23) . Outcome data were pooled using Mantel-Haenszel test, producing RR along with their 95% CI. Random-effect models were used given the initial sampling frame for the included studies. Statistical heterogeneity among studies was assessed using the I 2 statistic, with >50% indicative of high heterogeneity. The statistical analysis was done by two of the authors (GT and FDT). None of the authors had a direct role in data collection, the administration of the screening questionnaires, or the performance of the RT-PCR.

A total of 921 pediatric patients were included in the study. The median (IQR) age of our cohort is 6 (5-8) (range 2-18 years) (Fig. 1) . Table 2 depicts the characteristics of the study cohort. There was a J o u r n a l P r e -p r o o f comparable representation of males and females. Our cohort was largely comprised by Hispanics/Latinx which accounted for 63% of the subjects. Approximately 93% were covered by medical assistance programs from the Illinois Department of Healthcare and Family Services (Public Aid).

The overall SARS-CoV-2 positivity rate was 2.3% (21 of 921). Figure 1 shows the distribution of ages for the SARS-CoV-2 positive and negative groups. The median (IQR) age was 6 (5-8) for SARS-CoV-2 negative patients (range: 2-18 years) and 7 (4-8) for SARS-CoV-2 positive patients (range 2-12 years).

The age in both groups, however, was not statistically different. Age was also analyzed as a continuous variable. Under these circumstances, the association of age with SARS-CoV-2 remained not statistically significant (data not shown). Insurance status, past medical history, and dental diagnosis were comparable in both groups. Positivity rates were statistically higher for Hispanics/Latinx compared to other groups (p= 0.038); frequency values were 3.1% in Hispanics/Latinx, 1.4% in Whites, and zero in Blacks and Asians. The relative risk of Hispanics/Latinx having a positive SARS-CoV-2 test was 3.5 (95% confidence interval 1.04-11.7; p=0.040). No statistically significant differences were observed in the language of preference for Hispanics/Latinx with positive and negative SARS-CoV-2 tests.

The sex distribution among the SARS-CoV-2 positive children exhibited an almost double frequency of males (n=13) than females (n=8); however, this difference did not reached statistical significance (RR, 95% CI 1.55, 0.65-3.71; p=0.32). In pooled data analysis using information from other studies reporting rate of positivity in asymptomatic patients (n=2,393), males had a 1.97 increased risk (95% CI 1.08-3.62) of being positive for SARS-CoV-2 relative to females with an I 2 of 0% (Fig. 2 ).

In this study, we observed at low positivity rate of SARS-CoV-2 among asymptomatic pediatric dental patients. In addition, Hispanics/Latinx had a higher relative positivity risk than other sociodemographic groups. The true burden of asymptomatic pediatric cases is still unknown and several factors contribute to this problem, such as the age limits at certain testing centers, the discomfort associated with the swab and other factors (24, 25) . The rate of positivity of 2.3% observed in our cohort is higher than the 0.6% to J o u r n a l P r e -p r o o f 0.9% described in oncologic pediatric patients (9, 11) and closer to the 2.2% reported in surgical pediatric patients (10) . In comparison, our estimates are higher than the pooled prevalence of 0.65% reported by Sola et al. (2020) (14) . It should be noted that, in this last study, the prevalence of SARS-CoV-2 varied by region and ranged from 0% to 2.2%. Together, these findings suggest that the SARS-CoV-2 positivity rate is heterogeneously distributed in the general population. In our study, we had a higher representation of Hispanics/Latinx. Data from the Illinois Department of Public Health show that the positivity rate for SARS-CoV-2 infection is higher in Hispanics/Latinx than in other demographic groups (26). Our findings are in agreement with these estimates and support the notion that the implementation of SARS-CoV-2 testing may be particularly useful in pediatric dental clinics that provide care to sociodemographic groups with elevated prevalence of the disease based on local registries. In addition, our findings confirm that the implementation of questionnaires, though useful to identify high-risk individuals, does not completely eliminate the risk of SARS-CoV-2 spreading in dental offices.

Studies done in adult cohorts have consistently shown that males are more likely than females to experience severe COVID-19 disease (27) . It has been suggested that sex-specific differences in immunity may predispose males to develop a more robust inflammatory response against SARS-CoV-2

leading to systemic complications and death (28) . More recent data show that males and females have comparable prevalences (7) . In our study, we observed that males have a trend towards higher positivity rate of infection than females. This difference did not reach statistical significance but remained steady through the entire data collection period suggesting that our study could be underpowered to address this question. Using pooled data from other two studies that reported rate of positivity in pediatric cohorts, we confirmed that males have an approximately 2-fold increase in the risk of being positive for SARS-CoV-2 relative to females. From the pathogenic standpoint, it has been suggested that sex-specific factors may upregulate the expression of ACE2 in epithelial cells which is the binding site for SARS-CoV-2 in human cells (28) . However, due to the low sample size, the results of our pooled analysis should be interpreted with caution.

Our study has several limitations. First, the positivity rates in different demographic subgroups are likely to mirror the distribution of prevalences in the local community. Thus, our data do not necessarily prove that Hispanics/Latinx have an intrinsic susceptibility to the disease. It is likely that different socioeconomic factors may play a role in the increased positivity rate observed in this subpopulation. To this end, we did not have access to key information, such as ability of the parents or caregivers to exercise social distancing, access to remote work, household income, dwelling conditions and others which are likely to influence disease exposure. Second, our sample was skewed to include a higher proportion of The main strength of this study is its novelty, as this is the first report on positivity rate for SARS-CoV-2 in dentistry.

In our study, we observed that PCR testing for SARS-CoV-2 of asymptomatic patients adds value to the use of screening questionnaires for the identification of infected individuals who could be contagious.

Failure to identify these individuals may perpetuate the spread of the infection and have negative ramifications in the dental workforce. The positivity rate herein described in relatively low but within the range described in pediatric cohorts with medical conditions at large academic centers (9) (10) (11) 14) . The incidence of COVID-19 that would justify the use of PCR screening in a dental practice have not been established. It was been proposed that mass testing with the goal of identifying asymptomatic carriers may be a necessary and effective strategy to limit the spread of the disease (29) . Practical aspects should be considered prior to implementing such approach. The use of rapid COVID-19 antigen platforms J o u r n a l P r e -p r o o f in the dental office is a provocative idea and several models have been developed (30) . However, the cost of the diagnostic equipment and test kits can rapidly add to the increasing costs associated with the pandemic (31) . As an alternative, clinics can use decentralized diagnostic laboratories. Based on our own experience, however, these laboratories may favor providing services to large clinics in detriment of lowvolume offices. In addition, practices should adopt a flexible and streamlined scheduling process that allows bringing the patient back for treatment shortly after the testing. There is also the issue of patients or their parents not being amenable for nasopharyngeal swabbing. Based on our experience, it is important that clinics revisit their established workflow and confirm the feasibility of SARS-CoV-2 testing.

This requires identifying the suitable diagnostic test and allocating additional resources for phone screening, nasopharyngeal swabbing, and dynamic scheduling.

In conclusion, dental practices resuming care should consider adding SARS-CoV-2 testing to the use of screening tools, PPE and source control strategies prior to using aerosol generating procedures. This may be particularly important to reduce exposure in areas of elevated regional prevalence of SARS-CoV-2. 

COVID-19) Situation Reports

Illinois Department of Public Health. COVID-19 Statistics

Understanding pathways to death in patients with COVID-19

Frequency of Children vs Adults Carrying Severe Acute Respiratory Syndrome Coronavirus 2 Asymptomatically

Key Updates for Week 39

COVID-19 Cases, Deaths, and Trends in the US | CDC COVID Data Tracker

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units

COVID-19 in Children With Cancer

Incidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children's Hospitals

Clinical Screening for COVID-19 in Asymptomatic Patients With Cancer

Universal Screening for COVID-19 in Children Undergoing Orthopaedic Surgery: A Multicenter Report

Universal Screening for SARS-CoV-2 in Women Admitted for Delivery

Prevalence of SARS-CoV-2 Infection in Children Without Symptoms of Coronavirus Disease

Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses

Guidance for Dental Settings

Aerosols and splatter in dentistry: a brief review of the literature and infection control implications

ADA Interim Guidance for Minimizing Risk of COVID-19 Transmission

Center for Disease Control and Prevention. Coronavirus Disease 2020. Symptoms of Coronavirus

A Review of Acculturation Measures and Their Utility in Studies Promoting Latino Health

The Cochrane Collaboration

It's Not Easy to Get a Coronavirus Test for a Child. The New York Times

Is the coronavirus spreading silently among kids? Testing limits make it hard to tell

Pseudotumor cerebri syndrome associated with MIS-C: a case report

Considering how biological sex impacts immune responses and COVID-19 outcomes

The explosion of new coronavirus tests that could help to end the pandemic

Coronavirus testing finally gathers speed

Considerations for diagnostic COVID-19 tests

Within the last 2 weeks, have you (or your child) experience any of the following signs or symptoms? 2 weeks, have you (or your child) been exposed to a person who is known to have COVID-19 or SARS-CoV-2?

or your child) been exposed to a person who is under investigation for COVID-19 or SARS-CoV-2? Within the last 2 weeks, have you (or your child) been asked to self-isolate or quarantine? Within the last 2 weeks