key: cord-0896591-0its67c2
authors: Foster, Catherine E; Marquez, Lucila; Davis, Andrea L; Tocco, Elizabeth; Koy, Tjin H; Dunn, James; Revell, Paula A; Arrington, Amy S; Campbell, Judith R
title: A Surge in Pediatric Coronavirus Disease 2019 Cases: The Experience of Texas Children's Hospital from March to June 2020
date: 2020-12-10
journal: J Pediatric Infect Dis Soc
DOI: 10.1093/jpids/piaa164
sha: 4cab0fdef047fe02debe0af7431e77395eb7d656
doc_id: 896591
cord_uid: 0its67c2

BACKGROUND: An understanding of the clinical characteristics of children with coronavirus disease 2019 in diverse communities is needed to optimize the response of healthcare providers during this pandemic. METHODS: We performed a retrospective review of all children presenting to the Texas Children’s Hospital system with testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 10, 2020 through June 28, 2020.Demographics were recorded for all patients undergoing testing and clinical characteristics and outcomes were recorded for children with positive tests. RESULTS: Of 16,554 unique patients ≤ 21 years of age who were tested for SARS-CoV-2, 1215 (7.3%) patients tested positive. Infants under 1 year of age and patients aged 18-21 years had the highest percent of positive tests at 9.9% (230/2329) and 10.7% (79/739), respectively. Hispanic children accounted for 66% (802/1215) of positive tests, though they only represented 42.1% (6972/16554) of all children tested for SARS-CoV-2. Of the 1215 children with a positive test, 55.7% had fever, 40.9% had cough, 39.8% had congestion or rhinorrhea, 21.9% had gastrointestinal complaints, and 15.9% were asymptomatic. Only 97 (8%) patients were hospitalized (of which 68% were Hispanic). Most hospitalized patients had underlying medical conditions (62/97, 63.9%), including obesity. Thirty-one hospitalized patients (31/97, 32%) required respiratory support and nine patients (9/97, 9.3%) received SARS-CoV-2 antiviral therapy. Two patients died. CONCLUSIONS: A relatively high percentage of Hispanic children tested positive for SARS-CoV-2 and were hospitalized. Most children with detection of SARS-CoV-2 had uncomplicated illness courses, some children were critically ill, and two patients died.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID- 19) was declared a pandemic by the World Health Organization on March 11, 2020 [1] .There have been an astonishing 18.7 million cases globally and over 4.7 million cases with more than 156,000 deaths in the United States [2] .

The epidemiology of COVID-19 is well described in various adult populations from different geographic locations throughout the United States. Racial and ethnic disparities among adults with COVID-19 infection is now well described, but there are fewer reports on the impact of this emerging pandemic on the lives of children and adolescents from ethnically diverse urban communities [3] [4] [5] . While aspects of COVID-19 epidemiology, including hospitalization rates, severity of illness and underlying conditions, have been studied among children in the United States infected with SARS-CoV-2, little is known about potential racial and ethnic disparity among children [6] [7] [8] [9] . Otto and colleagues previously reported on a cohort of 424 children with SARS-CoV-2 infection across the Children's Hospital of Philadelphia Network [6] . Our report similarly contributes to the growing understanding of the epidemiology of SARS-CoV-2, while highlighting important demographic differences in a geographically distant part of the country. We additionally report on the presence of co-infections and radiographic and laboratory findings among children with SARS-CoV-2 infection.

The dynamics of the pandemic have varied between communities, as mitigating interventions and public health strategies across the nation have differed by state and within states. We previously reported on the clinical characteristics and outcomes of the first 57 consecutive cases of COVID-19 in children cared for through Texas Children's Hospital (TCH) [10] . As the pandemic has progressed, however, we experienced a surge of cases in Texas and a corresponding increase in the number of children infected with SARS-CoV-2 in the greater Houston area. This report serves to better characterize the epidemiology of A c c e p t e d M a n u s c r i p t 5 SARS-CoV-2 infection in children from infancy to young adulthood, who were seen throughout a large pediatric healthcare system at a time of increasing local transmission.

We performed a retrospective chart review of unique patients ≤ 21 years of age tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR) between the dates of 3/10/2020 -6/28/2020 through the TCH system. TCH is in Houston, Texas and is one of the largest specialty pediatric health care organizations in the United States. The TCH system serves the greater Houston area and consists of a large quaternary care pediatric hospital with over 600 beds within the Texas Medical Center and 2 community based pediatric hospitals in Katy, Texas and The Woodlands, Texas. In addition, our healthcare network has over 50 primary care locations (Texas Children's Pediatrics practices), 11 urgent care centers in the community and 3 Emergency centers within the hospitals. Epic (Epic Systems, Verona, WI) is the common electronic health care record for the TCH system.

We excluded patients who were tested through Texas Children's Employee Health and obstetrical patients cared for through the TCH Pavilion for Women. For patients with a positive test during the study timeframe, only the first positive test was included. For patients without a positive test, only the first test performed was included. Testing indications and demographic information (age, gender, race and ethnicity) was abstracted from the electronic medical record for all patients with a valid test result for a SARS-CoV-2 PCR during the study timeframe (3/10/2020-6/28/2020). A manual chart review was performed by 

During the study timeframe, TCH system-wide COVID-19 exposure and symptombased algorithms were utilized to guide clinical practice for SARS-CoV-2 testing, but testing was ultimately at provider discretion. Testing recommendations were revised based upon local epidemiology, updated CDC guidelines and increased testing capacity. Hospital-based testing for SARS-CoV-2 by PCR was initiated on March 10, 2020 and beginning March 22, 2020, surveillance testing for SARS-CoV-2 was implemented for all patients admitted to a pediatric intensive care unit or undergoing an aerosol generating procedure. A rapid PCR assay was available for patients undergoing emergent procedures. On May 14, 2020, surveillance testing was extended to include all patients needing admission to the pediatric hospitals at the medical center and community campuses. In general, outpatient testing algorithms prioritized testing of symptomatic patients with immunocompromising or chronic medical conditions or symptomatic patients with household contacts of a confirmed COVID-19 case or household contacts belonging to vulnerable populations. Testing of asymptomatic individuals, however, may have been performed due to exposure to a suspected or confirmed case of COVID-19 or due to requirements for childcare centers or camps. Drivethru testing locations have been in operation since March 24, 2020 with additional sites added April 28, 2020. SARS-CoV-2 testing indication, defined as surveillance or patient A c c e p t e d M a n u s c r i p t 7 under investigation (PUI), is recorded for both drive-thru tests and hospital-based tests and was implemented April 10, 2020.

Qualitative detection of SARS-CoV-2 RNA was performed using four different assays by the TCH Molecular Microbiology Laboratory during the study period. Acceptable and validated specimen types for testing included nasopharyngeal swabs, nasal washes and bronchial specimens. Specimens were placed in transport tubes containing 3. detection were carried out on the ABI7500 instrument (ThermoFisher). This test targets the E and S genes of SARS-CoV-2 and has a limit of detection of 0.1 PFU/mL [11] . The Simplexa COVID-19 Direct test (Diasorin Molecular, Cypress, CA) was performed according to the manufacturer's instructions for use [12] . This test targets the ORF1ab and S genes of SARS-CoV-2 and has a limit of detection of 500 copies/mL. The Aptima SARS-CoV-2 assay (Hologic, San Diego, CA) was performed according to the manufacturer's instructions for use [13] . This assay targets two different regions of the ORF1ab gene and has a limit of detection of 0.01 TCID50/mL. The Xpert Xpress SARS-CoV-2 test (Cepheid, Sunnyvale, CA) was performed according to the manufacturer's instructions for use [14] . The test targets the E and N2 genes of SARS-CoV-2 and has a limit of detection of 0.01 PFU/mL. Clinicians in the ambulatory setting could also order SARS-CoV-2 testing through a national reference laboratory (Quest Diagnostics).

A c c e p t e d M a n u s c r i p t 8

Descriptive statistics were used for analysis of demographic and clinical data (STATA 11.0, College Station, TX).

During the study period, 16,554 SARS-CoV-2 tests were performed on unique patients ≤ 21 years of age (see Supplemental Figure 1 ). Of these patients, 1215 (7.3%) patients tested positive for SARS-CoV-2 (Table 1) 

We performed a retrospective chart review of all pediatric patients tested for SARS-CoV-2 through the TCH system from March 10, 2020 through June 28, 2020. Of 16,554 unique patients ≤ 21 years, 1215 (7.3%) tested positive. We previously reported on the first 57 children with positive tests for SARS-CoV-2 in the very early stage of the pandemic, during a time of escalating public health measures to increase social distancing [10] .

Beginning in June, however, both the state of Texas and our local Houston area resumed activities in previously closed businesses, and we encountered a significant rise in the incidence of COVID-19 cases. An epidemic curve of our SARS-CoV-2 positive cases shows the increase in cases and the progression of the phased re-opening statutes which occurred in Texas in the preceding weeks ( Figure 1 ). Unfortunately, Texas has emerged as one the epicenters for COVID-19 in the Southern United States with at the peak reporting more than 50 SARS-CoV-2 cases daily among patients in the TCH system.

The TCH system serves the greater Houston metropolitan area which contains nine Texas counties, including over 4.7 million people in Harris County. Harris County is racially and ethnically diverse with 54% Whites, 19% Blacks/African American, 15% some other race, 7% Asian, 3% multiracial, and <1% each American Indian/Alaskan Native and Native

Hawaiian/Pacific Islander [15] . The Hispanic community comprises 43% of Harris County [15] . In our study, Hispanic children disproportionately tested positive for SARS-CoV-2. Consistent with other international and domestic pediatric studies, we found that most children with COVID-19 had a mild clinical course [6, [17] [18] [19] [20] [21] [22] . Fever and cough were the most common symptoms in our study and 15.9% of children were asymptomatic. Infants have previously been identified as a population at increased risk of hospitalization and potentially of severe disease with COVID-19 [22] . In a multinational study of children and adolescents in Europe, investigators found COVID-19 to cause a generally mild disease in children including infants, though age <1 month was associated with a need for intensive care unit admission [19] . In one report of SARS-CoV-2 positive infants <90 days of age, 50% (9/18) were hospitalized but none required intensive care [23] . In another pediatric study based in New York, investigators found that obesity was significantly associated with severe disease, but infants and immunocompromised patients were not at increased risk [7] .

In our study, infants also had mild illness; one infant required intensive care and one infant was found to have a urinary tract infection.

Overall, we found that a relatively low percentage of patients with SARS-CoV-2 were hospitalized (97/1215, 8%) and furthermore over 40% of the admitted patients had a primary diagnosis other than COVID-19. Interestingly, 12 patients were hospitalized with acute A c c e p t e d M a n u s c r i p t 12 appendicitis. There are case reports detailing clinical presentations of COVID-19 mimicking appendicitis [24] . Appendicitis is the most common pediatric surgical diagnosis, however, and the relationship between SARS-CoV-2 and appendicitis remains unclear and warrants further investigation. Both pediatric and adult reports have found lymphopenia to be a common laboratory finding in patients with COVID-19, though this finding was only present in 30.7% of our admitted patients [7, 25] .

Our study has several limitations that warrant acknowledgment, including those inherent in a retrospective chart review. Although TCH is the largest pediatric specialty care network in the area, we would not have captured patients presenting outside of our system or patients transferred into our system if a SARS-CoV-2 PCR was not performed at TCH. This study by examining all children tested for SARS-CoV-2 across a large pediatric healthcare system in a diverse population provides insight into disproportionate effects of COVID-19 among racial and ethnic minorities. Overall, most children with detection of SARS-CoV-2 had uncomplicated illness courses, children who were hospitalized often had underlying medical conditions, and fatal outcomes were rare. M a n u s c r i p t 17 M a n u s c r i p t test for severe acute  respiratory syndrome coronavirus 2 at Texas Children's Hospital from March 23, 2020 through June 28, 2020. Reopening phase 1 in the state of Texas included operation of retail stores, restaurants, movie theaters, malls, museums, and libraries at 25% capacity effective May 1, 2020. On May 5, 2020, barbershops, cosmetology businesses, hair salons and gyms were permitted to reopen. Phase 2 included reopening of restaurants at 50% capacity, bars at 25% capacity, and childcare facilities and bowling alleys on May 18, 2020. Phase 3 reopening allowed all businesses to operate at 50% capacity on June 3, 2020. On June 12, 2020 restaurants were permitted to operate at 75% capacity.

M a n u s c r i p t 20 Figure 1 

World Health Organization

COVID-19): cases in the

Hospitalization and Mortality among Black Patients and White Patients with Covid-19

Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs

Ethnicity and COVID-19 in children with comorbidities

The Epidemiology of SARS-CoV-2 in a

Pediatric Healthcare Network in the United States

Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in

SARS-CoV-2 Infection in Febrile Neonates

Characteristics of Hospitalized Pediatric COVID-19 Cases

Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes

Food and Drug Administration (FDA) emergency use authorization (EUA) instructions for use (IFU)

Diasorin Molecular Inc. Simplexa COVID-19 Direst test. U.S. Food and Drug Administration (FDA) emergency use authorization (EUA) instructions for use (IFU)

Food and Drug Administration (FDA) emergency use authorization (EUA) instructions for use (IFU)

Food and Drug Administration (FDA) emergency use authorization (EUA) instructions for use (IFU)

Demographics Dashboard. Summary Data for County: Harris. Available at

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 -COVID-NET, 14 States

Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in

Coronavirus Infection in Pediatric Emergency Departments Research G. Children with Covid-19 in Pediatric Emergency Departments in Italy

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Epidemiology of COVID-19 Among Children in China

Report on the Epidemiological Features of Coronavirus Disease 2019 (COVID-19) Outbreak in the Republic of Korea from

Coronavirus Disease 2019 in Children -United States

SARS-CoV-2 Infection in Infants Less than 90 Days Old

Can COVID 19 present like appendicitis?

Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

Native Hawaiian and Other Pacific Islander, n (%)

Reason for Testing Patient Under Investigation (PUI), n (%)

The authors would like to acknowledge the sustained efforts of the healthcare team and frontline staff in all TCH locations during the COVID-19 pandemic.