Common seasonal respiratory viral infections in children before and during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVES: To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients. DESIGN: A retrospective cross-sectional study including patient admissions to the Children's National Hospital between October 1, 2015, and December 31, 2020. RESULTS: Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05). CONCLUSIONS: Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Kinetics of Viral Clearance and Antibody Production Across Age Groups in Children with Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVES: To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: This retrospective analysis of children tested for SARS-CoV-2 by reverse transcription (RT) polymerase chain reaction (PCR) and immunoglobulin G antibody at a quaternary-care, free-standing pediatric hospital between March 13, 2020, and June 21, 2020, included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity. RESULTS: The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and time from RT-PCR positivity to negativity was 25 days. Of note, patients aged 6 through 15 years demonstrated a longer time of RT-PCR positivity to negativity, compared with patients aged 16 through 22 years (median 32 vs 18 days, P = .015). Median time to seropositivity, by chemiluminescent testing, from RT-PCR positivity was 18 days, whereas median time to reach adequate levels of neutralizing antibodies (defined as comparable with 160 titer by plaque reduction neutralization testing) was 36 days. CONCLUSIONS: The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. It is unknown whether this correlates with persistent infectivity. Only 17 of 33 patients demonstrated adequate neutralizing antibodies during the time frame of specimen collection. It remains unknown whether immunoglobulin G antibody against spike structured proteins correlates with immunity, and how long antibodies and potential protection persist.

Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children.

Importance: Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective: To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants: This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children's National Hospital in the District of Columbia. Exposures: COVID-19 or influenza A or B. Main Outcomes and Measures: Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results: The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance: In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.