SARS-CoV-2 Infections in Children — Multi-Center Surveillance, United States, January–March 2020

Abstract Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January–March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2–positive cases were identified March 20–31 despite evidence of rising community circulation.


Background
As of May 24, 2020, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had resulted in 1,622,114 reported US cases and 97,049 deaths [1]. Previous US reports of COVID-19 among children relied on clinician-ordered testing and health jurisdiction reporting to the Centers for Disease Control and Prevention (CDC) [2,3]; we present preliminary SARS-CoV-2 data collected during active surveillance of pediatric acute respiratory illness (ARI) through CDC's New Vaccine Surveillance Network (NVSN) January-March 2020.

Methods
NVSN active, prospective, population-based ARI surveillance among children aged <18 years was re-established in 2015 and is conducted at 7 US pediatric medical centers (Table) [4,5].
Children presenting with ≥1 ARI symptom and/or fever were eligible for enrollment in inpatient, emergency department (ED), or outpatient clinic settings, as were asymptomatic controls presenting for well-child visits. Enrollment criteria by clinical setting with full list of eligible symptoms and age ranges are described in Table 1. Institutional review board approvals were obtained at CDC and at each institution; prior to enrollment, parental informed consent was obtained for parent/guardian interview, medical record review, and respiratory specimen collection with approval for storage and future testing for respiratory pathogens.
Specimens were tested using validated real-time reverse transcription polymerase-chain reaction (RT-PCR) assays based on CDC primers and probes [6]. Positive Seattle-site specimens were retested with a second RT-PCR assay and considered inconclusive if the second test was not positive [7]; when possible, inconclusive specimens were retested a third time using the CDCbased RT-PCR assay to yield a final result. Preliminary clinical and demographic data were used in descriptive analyses. To document SARS-CoV-2 circulation in surveillance areas, weekly numbers of COVID-19 cases for all ages reported from counties in which most NVSN enrollees reside were analyzed for January 1-April 4, 2020 [8].

Discussion
Few pediatric SARS-CoV-2-positive cases were detected through systematic surveillance during January-March, despite evidence of rising circulation in the surrounding communities in March.
These low numbers are consistent with previous US reports showing children constitute a small minority of reported COVID-19 cases [2,3]. From February 12 to April 2, only 1.7% of cases reported to CDC by local US jurisdictions occurred in children, though 22% of the US population is <18 years old [2]. In addition, although surveillance testing was performed on specimens collected from children enrolled as early as January or February, all 4 COVID-19 cases were detected in late March, which may reflect that community transmission was limited earlier in the year, consistent with other findings from US surveillance [8,10].
Study limitations include possible missed detections because only 59% of eligible children were enrolled, lack of enrollment of older children in outpatient settings, and suspended or limited surveillance due to pandemic-related restrictions during March while community circulation appeared to be rising. Testing algorithms were not standardized across sites and each site validated and conducted their own testing. Differences in test performance by site (including the possibility of false-positive results) were not evaluated.

Strengths of this surveillance included broad inclusion criteria and testing not reliant on clinical
testing practices, which revealed that >99% of children tested at the 7 sites from January-March were SARS-CoV-2-negative. As US cases increase, continued surveillance is needed to elucidate COVID-19 epidemiology in children.  b Children aged <18 years were eligible for enrollment if they resided in the center's surveillance area and visited the ED or were admitted to the hospital in the 48 hours preceding enrollment with ≥1 of the following presenting symptoms/events: fever, cough, earache, nasal congestion, runny nose, sore throat, vomiting after coughing, wheezing, shortness of breath/rapid or shallow breathing, apnea, apparent life-threatening event or brief resolved unexplained event, or myalgias; and the duration of illness that led to the hospitalization/visit was <14 days. Children were excluded if they had a known non-respiratory cause for the hospitalization/visit, had fever and neutropenia from chemotherapy, had been transferred from another hospital after admission of >48 hours, were admitted <5 days of a previous hospitalization, had never been discharged home after birth, or had previous enrollment in the study <14 d ays prior to current admission/visit. c Children aged <24 months were eligible for enrollment if they resided in the center's surveillance area and presented to clinic with ≥1 of the following symptoms/events: fever, cough, earache, nasal congestion, runny nose, sore throat, wheezing, or shortness of breath/rapid or shallow breathing; and the duration of illness that led to the visit was <14 days. Children were excluded if they had a known non-respiratory cause for the outpatient visit, had fever and neutropenia from chemotherapy, were seen at the clinic within 5 days after an ARI hospitalization/ED visit, or had been enrolled as outpatients within the previous 4 days. d Children were eligible for enrollment as asymptomatic controls if they were aged >14 days to <5 years, resided in the center's surveillance area, and were evaluated at a routine (e.g., well-child) outpatient visit with no cough, earache, fever, nasal congestion, runny nose, shortness of breath/rapid or shallow breathing, sore throat, vomiting after cough, or wheezing on the day of visit or 3 days preceding the visit, and no diarrhea or vomiting on the day of visit or 14 days preceding the visit. In addition, children were excluded if they were immunocompromised, had been previously enrolled as a healthy control in the same season, or had a sibling enrolled during the same visit.

Figure Legends
Figure 1: SARS-CoV-2 cases detected by the New Vaccine Surveillance Network (NVSN) by site among children <18 years of age and weekly health jurisdiction reports of cases by main surveillance counties among all ages [8]