SARS-CoV-2 Infection Mitigation Strategies Concomitantly Reduce Group A Streptococcus Pharyngitis

Introduction

Group A streptococcus (GAS) is the most common cause of pediatric bacterial pharyngitis.^1,2 Children are the primary reservoir for GAS and represent the pool from which children and adults acquire infection. The bacteria are spread person-to-person by contacting secretions or articles/surfaces contaminated by infected individuals.^1,2 Thus, eliminating these transmission sources should reduce the burden of GAS pharyngitis (GAS-P). Implementation of infection mitigation strategies (IMS) to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic provided an opportunity to study the impact of such measures on the GAS-P burden. The goal of this study was to characterize the impact of SARS-CoV-2 IMS on pediatric cases of GAS-P and determine whether the pandemic caused inequalities in how patients used our health care system.

Methods

This retrospective case-series chart review study was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences (No. 274080). Arkansas Children’s Hospital is a tertiary care facility in Little Rock, Arkansas, and includes a level 1 emergency department (ED) and 7 outpatient (OP) clinics. All patients tested for GAS-P from April 1, 2018, to December 31, 2019, and from April 1, 2020, to December 31, 2021, were identified from our integrated electronic health record (Epic Systems, Verona, Wisconsin). Patient-specific information (age at the time of testing, date/location of testing [ED or OP], sex, race/ethnicity) was obtained. All testing used the Sofia Strep A FIA (Quidel, San Diego, California) point-of-care rapid antigen test (RAT); all negative RATs were confirmed by nucleic acid amplification (Solana GAS Assay [Quidel] or GeneXpert Xpress Strep A [Cepheid, Sunnyvale, California]). A patient was considered GAS-positive if RAT was positive or if RAT was negative and confirmation testing was positive. A patient was considered GAS-negative if both RAT and confirmation testing were negative. To avoid counting multiple test results for the same episode of GAS-P, repeat test results within 14 days, if encountered, were excluded. In Arkansas, SARS-CoV-2 IMS began late March 2020 and included universal masking, physical distancing, restricted access to public activities, and temporary cessation of in-person school and extracurricular activities, including daycare facilities. Frequent hand hygiene and cleansing of high-contact surfaces were highly recommended. In August 2021, students opted to learn virtually or in-person, the latter requiring continued use of universal masking and physical distancing. Data were sorted into SARS-CoV-2 pre-mitigation (April 2018-December 2019) and mitigation (April 2020-December 2021) periods. Subgroup stratification included patient location (ED vs. OP) (emergency department vs outpatient) and patient age groups: 0-5 years, 6-10 years, 11-13 years, 14-18 years. Descriptive statistics were used to tabulate the test positivity rate and the interval change in the positivity rate (pre-mitigation period minus mitigation period). Chi-square (χ²-independence) analysis was used to determine the statistical difference of the interval change in the positivity rate. All statistical analyses were performed with Microsoft Excel 365 (Microsoft Corp., Redmond, Washington); P values <.05 were considered significant.

Results

During the two 21-month periods, 17 979 tests for GAS-P were performed on 14 675 patients (≤18 years; 54% female). There were no instances of repeat test results within 14 days for any patient evaluated for GAS-P. During the pre-mitigation time period, the incidence of GAS-P was 181.8 cases per 1000 visits (19 316 visits for pharyngitis, 3512 cases of GAS-P). During the mitigation time period, the incidence of GAS-P was 33.5 cases per 1000 visits (11 421 visits for pharyngitis, 1013 cases of GAS-P). After the implementation of IMS, the incidence of GAS-P dropped by 81.6% (P < .0001). The temporal relationship of the total number of tests performed and the overall GAS-P test positivity rate is depicted in Figure 1A. Table 1 summarizes patient demographic information, the GAS-P test positivity rates for the pre-mitigation and mitigation periods, and the interval reduction in the GAS-P test positivity rate after IMS implementation. In addition, these data are presented in aggregate, as well as stratified by patient location (ED vs. OP). In the pre-mitigation period, 12 135 tests were performed with a positivity rate of 28.9%. In the mitigation period, 5844 tests were performed with a positivity rate of 17.3%. The 40.1% reduction in the overall positivity rate observed after implementing IMS was statistically significant (P < .001). For patients evaluated in the ED, 6160 (pre-mitigation) and 4217 (mitigation) tests were performed with a positivity rate of 27.1% and 16.0%, respectively. For patients evaluated in the OP setting, 5975 (pre-mitigation) and 1627 (mitigation) tests were performed with a positivity rate of 30.9% and 20.8%, respectively. The positivity rate reductions for ED (40.9%) and OP (32.7%) were statistically significant (P < .001). Age subgroups (0-5, 6-10, 11-13, 14-18 years) were chosen to correlate with education level (preschool, elementary, middle, high school), respectively. Implementing IMS led to statistically significant reductions in positivity rates (range, 19.6%-46.2%) for each age group, regardless of where patients were evaluated. Specifically, the reduction in the positivity rate was most prominent in the younger age groups (Figure 1B). There was an approximately 6% incremental reduction in the positivity rate for each successively younger age group (preschool, 42.1%; elementary school, 40.1%; middle school, 35.5%; high school, 23.9%). Racial/ethnic distribution of patients evaluated in the ED and OP setting is depicted in Figure 1C. For ED, racial/ethnic distribution was equivalent in both the pre-mitigation and mitigation periods, respectively: black (51%, 50.7%), white (34.3%, 32.4%), Hispanic (11.7%, 12.9%), other (3.1, 3.9%). For OP, racial/ethnic distribution ranged from equivalent to slightly variable (nonstatistically significant) in the pre-mitigation and mitigation periods: black (36.6%, 36.5%), white (33.6%, 25.9%), Hispanic (26.3%, 34%), other (3.5%, 3.5%).

Figure 1.

(A) Summary of GAS-P tests results from April 1, 2018, to December 31, 2019 (pre-SARS-CoV-2 period) and April 1, 2020, to December 31, 2021 (SARS-CoV-2 period). Q1, January-March; Q2, April-June; Q3, July-September; Q4, October-December. Black vertical broken line indicates implementation of IMS. Number of tests performed per quarter (columns) and GAS-P test positivity rates (curvilinear lines) for emergency department (black) and outpatient (gray) settings. (B) Linear relationship of age group and magnitude of percent reduction in the GAS-P positivity rate with implementation of IMS. (C) Racial/ethnic distribution of patients evaluated in the emergency department (black) or outpatient (gray) settings. Pre-IMS, period before implementing infection mitigation strategies (IMS); IMS, period with implementation of IMS.

Table 1.

Summary of Patient Demographics, GAS-P Test Positivity Rates, and Interval Change (Percent Change in GAS-P Positivity Rate After Implementing IMS).

Demographic information			Pre-mitigation period (April 2018-December 2019)			Mitigation period (April 2020-December 2021)			Interval change	χ2
Location	Age, y	Unique patients	Positive tests	Total tests	% Positive	Positive tests	Total tests	% Positive	(%)	P value
All	All	14 675	3512	12 135	28.9	1013	5844	17.3	−40.1	<.001
	0-5	5348	1233	4287	28.8	328	1969	16.7	−42.1	<.001
	6-10	5104	1556	4275	36.4	412	1889	21.8	−40.1	<.001
	11-13	2098	426	1636	26.0	135	804	16.8	−35.5	<.001
	14-18	2642	297	1937	15.3	138	1182	11.7	−23.9	<.001
ED	All	8788	1668	6160	27.1	675	4217	16.0	−40.9	<.001
	0-5	3488	660	2439	27.1	221	1518	14.6	−46.2	<.001
	6-10	2903	693	2071	33.5	276	1321	20.9	−37.6	<.001
	11-13	1127	173	725	23.9	83	545	15.2	−36.2	<.001
	14-18	1523	142	925	15.4	95	833	11.4	−25.7	<.05
OP	All	5887	1844	5975	30.9	338	1627	20.8	−32.7	<.001
	0-5	1860	573	1848	31.0	107	451	23.7	−23.5	<.05
	6-10	2201	863	2204	39.2	136	568	23.9	−38.9	<.001
	11-13	971	253	911	27.8	52	259	20.1	−27.7	<.05
	14-18	1119	155	1012	15.3	43	349	12.3	−19.6	.17

Abbreviations: ED, emergency department; OP, outpatient.

Discussion

To attenuate the SARS-CoV-2 pandemic, various IMS were implemented, including universal masking, physical distancing, restricted access to public activities, cessation of in-person school and extracurricular activities, heightened hand hygiene, and frequent cleansing of high-contact surfaces. Such IMS have demonstrated statistically significant reductions in the incidence of numerous pediatric infections, including acute otitis media, common cold, croup, gastroenteritis, pneumococcal pneumonia, pharyngitis (GAS and nonstreptococcal), pneumonia, otorrhea, and sinusitis.^3-10 Collectively, reductions in the incidence of the following bacterial and viral infectious agents were observed: adenovirus, bocavirus, coronaviruses (HKU1, OC43, NL63, 229E), enterovirus/rhinovirus, human metapneumovirus, influenza, methicillin-resistant Staphylococcus aureus, parainfluenza virus types 1-4, respiratory syncytial virus, and Streptococcus pneumoniae.^3-10 With respect to GAS-P, reduced incidence or prevalence of pediatric cases has been documented in the North Central and Northeastern United States.^4,8 Similarly, we demonstrated a significant reduction in pediatric GAS-P after implementing IMS in the South Central United States. To the best of our knowledge, we are first to perform age-based subgroup analyses of the pediatric population and report the inverse relationship between children age groups and the magnitude of the percent reduction in the GAS-P positivity rate after implementing IMS. In short, we observed an approximate 6% incremental reduction in the GAS-P positivity rate for each successively younger age group (preschool [0-5 years], 42.1%; elementary school [6-10 years], 40.1%; middle school [11-13 years], 35.5%; high school [14-18 years], 23.9%). This finding supports the conclusion that SARS-CoV-2 IMS had the greatest benefit in the youngest patients. This observation was unexpected considering the inherent challenges parents/custodians faced when trying to enforce IMS in preschool (0-5 years), and to a lesser extent, elementary school (6-10 years) children. This finding is likely due to the closure of daycare facilities and schools, essentially eliminating the comingling of children in this age group. In addition, any degree of compliance with IMS from middle school (11-13 years), high school (14-18 years), and adults (>19 years) would incrementally decrease the overall burden of GAS-P within a population, possibly even reducing the “carrier state” as previously described. ² The racial/ethnic distribution of patients using our health care system, either the ED or OP setting, for evaluation of GAS-P remained essentially unchanged in the pre-IMS and IMS periods. If present, any bias in how patients of varying races/ethnicities accessed our health care system was independent of the SARS-CoV-2 pandemic.

There are limitations to our study which are accordingly acknowledged. First, we were unable to determine the number of children in this study with viral pharyngitis. A significant proportion of these children may also have been tested and determined to be negative for GAS, thereby lowering the observed GAS-P positivity rate. It is well established that upper respiratory tract viruses are the single most common cause of pharyngitis in the pediatric population, accounting for 25% to 45% of cases. ¹¹ These include adenovirus, bocavirus, coronaviruses (229E, HKU1, NL63, OC43), enterovirus/rhinovirus, human metapneumovirus, influenza A/B, parainfluenza (types 1-4), and respiratory syncytial virus. ¹¹ Prior to the SARS-CoV-2 pandemic, these viruses readily circulated. Of note, the frequency of these viruses was reduced to 1% or less during the SARS-CoV-2 pandemic. ³ However, 2 recently published meta-analyses demonstrated that pharyngitis was only observed in 5% to 22% of children with SARS-CoV-2 infection.^12,13 Any impact that circulating respiratory viruses may have had on GAS-P positivity rates would have been more pronounced prior to the SARS-CoV-2 pandemic. Therefore, our observed reduction in the GAS-P positivity rate is likely independent of the number of children with viral pharyngitis. Second, our results were generated from a single pediatric hospital network that essentially represented the metropolitan area of Little Rock, AR, and may not be reflective of other urban and rural pediatric populations. Finally, we highlight a temporal association between IMS implementation and the reduction in pediatric GAS-P. Although a causal relationship cannot be definitively established, our data are in alignment with others and collectively provide additional evidence for such a relationship.

Conclusions

The SARS-CoV-2 IMS effectively reduced the burden of GAS-P in our pediatric population. The magnitude was most pronounced in the youngest age group (<10 years of age). Any bias in how patients of varying races/ethnicities accessed our health care system was independent of the SARS-CoV-2 pandemic.

Author Contribution

BLB: Contributed to conception and design; contributed to acquisition, analysis, or interpretation; drafted the manuscript; critically revised the manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring integrity and accuracy.

JNS: Contributed to conception and design; contributed to analysis or interpretation; critically revised the manuscript, gave final approval; agrees to be accountable for all aspects of work ensuring integrity and accuracy.

RAF: Contributed to conception and design; contributed to acquisition, analysis, or interpretation; drafted the manuscript; critically revised the manuscript; gave final approval, agrees to be accountable for all aspects of work ensuring integrity and accuracy.

ERR: Contributed to conception and design; contributed to analysis or interpretation; drafted the manuscript, critically revised the manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring integrity and accuracy.

HLY: Contributed to conception and design; contributed to analysis or interpretation; drafted the manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring integrity and accuracy.

JLK: Contributed to conception and design; contributed to analysis or interpretation; drafted the manuscript; critically revised the manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring integrity and accurary.