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

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          Abstract

          This cohort study compares the clinical features of coronavirus disease 2019 (COVID-19) with those of influenza A and B in US children.

          Key Points

          Question

          What are the similarities and differences in clinical features between coronavirus disease 2019 (COVID-19) and seasonal influenza in US children?

          Findings

          In this cohort study of 315 children with COVID-19 and 1402 children with seasonal influenza, there were no statistically significant differences in the rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use between the 2 groups. More patients with COVID-19 than with seasonal influenza reported fever, diarrhea or vomiting, headache, body ache, or chest pain at the time of diagnosis.

          Meaning

          The findings suggest that prevention of both COVID-19 and seasonal influenza in US children is prudent and urgent for the well-being of this population.

          Abstract

          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.

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          Most cited references16

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          Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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            Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

            Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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              Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020

              On April 6, 2020, this report was posted online as an MMWR Early Release. As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States ( 1 , 2 ). In the United States, 22% of the population is made up of infants, children, and adolescents aged * Includes infants, children, and adolescents. † Excludes 23 cases in children aged <18 years with missing report date. § Date of report available starting February 24, 2020; reported cases include any with onset on or after February 12, 2020. The figure is a combination epidemiological curve and line graph showing 2,549 cases of COVID-19 in children aged <18 years in the United States, by date reported to CDC during February 24–April 2, 2020. Among all 2,572 COVID-19 cases in children aged <18 years, the median age was 11 years (range 0–17 years). Nearly one third of reported pediatric cases (813; 32%) occurred in children aged 15–17 years, followed by those in children aged 10–14 years (682; 27%). Among younger children, 398 (15%) occurred in children aged <1 year, 291 (11%) in children aged 1–4 years, and 388 (15%) in children aged 5–9 years. Among 2,490 pediatric COVID-19 cases for which sex was known, 1,408 (57%) occurred in males; among cases in adults aged ≥18 years for which sex was known, 53% (75,450 of 143,414) were in males. Among 184 (7.2%) cases in children aged <18 years with known exposure information, 16 (9%) were associated with travel and 168 (91%) had exposure to a COVID-19 patient in the household or community. Data on signs and symptoms of COVID-19 were available for 291 of 2,572 (11%) pediatric cases and 10,944 of 113,985 (9.6%) cases among adults aged 18–64 years (Table). Whereas fever (subjective or documented), cough, and shortness of breath were commonly reported among adult patients aged 18–64 years (93% reported at least one of these), these signs and symptoms were less frequently reported among pediatric patients (73%). Among those with known information on each symptom, 56% of pediatric patients reported fever, 54% reported cough, and 13% reported shortness of breath, compared with 71%, 80%, and 43%, respectively, reporting these signs and symptoms among patients aged 18–64 years. Myalgia, sore throat, headache, and diarrhea were also less commonly reported by pediatric patients. Fifty-three (68%) of the 78 pediatric cases reported not to have fever, cough, or shortness of breath had no symptoms reported, but could not be classified as asymptomatic because of incomplete symptom information. One (1.3%) additional pediatric patient with a positive test result for SARS-CoV-2 was reported to be asymptomatic. TABLE Signs and symptoms among 291 pediatric (age <18 years) and 10,944 adult (age 18–64 years) patients* with laboratory-confirmed COVID-19 — United States, February 12–April 2, 2020 Sign/Symptom No. (%) with sign/symptom Pediatric Adult Fever, cough, or shortness of breath† 213 (73) 10,167 (93) Fever§ 163 (56) 7,794 (71) Cough 158 (54) 8,775 (80) Shortness of breath 39 (13) 4,674 (43) Myalgia 66 (23) 6,713 (61) Runny nose¶ 21 (7.2) 757 (6.9) Sore throat 71 (24) 3,795 (35) Headache 81 (28) 6,335 (58) Nausea/Vomiting 31 (11) 1,746 (16) Abdominal pain¶ 17 (5.8) 1,329 (12) Diarrhea 37 (13) 3,353 (31) *Cases were included in the denominator if they had a known symptom status for fever, cough, shortness of breath, nausea/vomiting, and diarrhea. Total number of patients by age group: <18 years (N = 2,572), 18–64 years (N = 113,985). † Includes all cases with one or more of these symptoms. § Patients were included if they had information for either measured or subjective fever variables and were considered to have a fever if “yes” was indicated for either variable. ¶ Runny nose and abdominal pain were less frequently completed than other symptoms; therefore, percentages with these symptoms are likely underestimates. Information on hospitalization status was available for 745 (29%) cases in children aged <18 years and 35,061 (31%) cases in adults aged 18–64 years. Among children with COVID-19, 147 (estimated range = 5.7%–20%) were reported to be hospitalized, with 15 (0.58%–2.0%) admitted to an ICU (Figure 2). Among adults aged 18–64 years, the percentages of patients who were hospitalized (10%–33%), including those admitted to an ICU (1.4%–4.5%), were higher. Children aged <1 year accounted for the highest percentage (15%–62%) of hospitalization among pediatric patients with COVID-19. Among 95 children aged <1 year with known hospitalization status, 59 (62%) were hospitalized, including five who were admitted to an ICU. The percentage of patients hospitalized among those aged 1–17 years was lower (estimated range = 4.1%–14%), with little variation among age groups (Figure 2). FIGURE 2 COVID-19 cases among children* aged <18 years, among those with known hospitalization status (N = 745),† by age group and hospitalization status — United States, February 12–April 2, 2020 Abbreviation: ICU = intensive care unit. * Includes infants, children, and adolescents. † Number of children missing hospitalization status by age group: <1 year (303 of 398; 76%); 1–4 years (189 of 291; 65%); 5–9 years (275 of 388; 71%); 10–14 years (466 of 682; 68%); 15–17 years (594 of 813; 73%). The figure is a bar chart showing 745 U.S. COVID-19 cases among children aged <18 years with known hospitalization status, by age group and hospitalization status during February 12–April 2, 2020. Among 345 pediatric cases with information on underlying conditions, 80 (23%) had at least one underlying condition. The most common underlying conditions were chronic lung disease (including asthma) (40), cardiovascular disease (25), and immunosuppression (10). Among the 295 pediatric cases for which information on both hospitalization status and underlying medical conditions was available, 28 of 37 (77%) hospitalized patients, including all six patients admitted to an ICU, had one or more underlying medical condition; among 258 patients who were not hospitalized, 30 (12%) patients had underlying conditions. Three deaths were reported among the pediatric cases included in this analysis; however, review of these cases is ongoing to confirm COVID-19 as the likely cause of death. Discussion Among 149,082 U.S. cases of COVID-19 reported as of April 2, 2020, for which age was known, 2,572 (1.7%) occurred in patients aged <18 years. In comparison, persons aged <18 years account for 22% of the U.S. population ( 3 ). Although infants <1 year accounted for 15% of pediatric COVID-19 cases, they remain underrepresented among COVID-19 cases in patients of all ages (393 of 149,082; 0.27%) compared with the percentage of the U.S. population aged <1 year (1.2%) ( 3 ). Relatively few pediatric COVID-19 cases were hospitalized (5.7%–20%; including 0.58%–2.0% admitted to an ICU), consistent with previous reports that COVID-19 illness often might have a mild course among younger patients ( 4 , 5 ). Hospitalization was most common among pediatric patients aged <1 year and those with underlying conditions. In addition, 73% of children for whom symptom information was known reported the characteristic COVID-19 signs and symptoms of fever, cough, or shortness of breath. These findings are largely consistent with a report on pediatric COVID-19 patients aged <16 years in China, which found that only 41.5% of pediatric patients had fever, 48.5% had cough, and 1.8% were admitted to an ICU ( 4 ). A second report suggested that although pediatric COVID-19 patients infrequently have severe outcomes, the infection might be more severe among infants ( 5 ). In the current analysis, 59 of 147 pediatric hospitalizations, including five of 15 pediatric ICU admissions, were among children aged <1 year; however, most reported U.S. cases in infants had unknown hospitalization status. In this preliminary analysis of U.S. pediatric COVID-19 cases, a majority (57%) of patients were males. Several studies have reported a majority of COVID-19 cases among males ( 4 , 9 ), and an analysis of 44,000 COVID-19 cases in patients of all ages in China reported a higher case-fatality rate among men than among women ( 10 ). However, the same report, as well as a separate analysis of 2,143 pediatric COVID-19 cases from China, detected no substantial difference in the number of cases among males and females ( 5 , 10 ). Reasons for any potential difference in COVID-19 incidence or severity between males and females are unknown. In the present analysis, the predominance of males in all pediatric age groups, including patients aged <1 year, suggests that biologic factors might play a role in any differences in COVID-19 susceptibility by sex. The findings in this report are subject to at least four limitations. First, because of the high workload associated with COVID-19 response activities on local, state, and territorial public health personnel, a majority of pediatric cases were missing data on disease symptoms, severity, or underlying conditions. Data for many variables are unlikely to be missing at random, and as such, these results must be interpreted with caution. Because of the high percentage of missing data, statistical comparisons could not be conducted. Second, because many cases occurred only days before publication of this report, the outcome for many patients is unknown, and this analysis might underestimate severity of disease or symptoms that manifested later in the course of illness. Third, COVID-19 testing practices differ across jurisdictions and might also differ across age groups. In many areas, prioritization of testing for severely ill patients likely occurs, which would result in overestimation of the percentage of patients with COVID-19 infection who are hospitalized (including those treated in an ICU) among all age groups. Finally, this analysis compares clinical characteristics of pediatric cases (persons aged <18 years) with those of cases among adults aged 18–64 years. Severe COVID-19 disease appears to be more common among adults at the high end of this age range ( 6 ), and therefore cases in young adults might be more similar to those among children than suggested by the current analysis. As the number of COVID-19 cases continues to increase in many parts of the United States, it will be important to adapt COVID-19 surveillance strategies to maintain collection of critical case information without overburdening jurisdiction health departments. National surveillance will increasingly be complemented by focused surveillance systems collecting comprehensive case information on a subset of cases across various health care settings. These systems will provide detailed information on the evolving COVID-19 incidence and risk factors for infection and severe disease. More systematic and detailed collection of underlying condition data among pediatric patients would be helpful to understand which children might be at highest risk for severe COVID-19 illness. This preliminary examination of characteristics of COVID-19 disease among children in the United States suggests that children do not always have fever or cough as reported signs and symptoms. Although most cases reported among children to date have not been severe, clinicians should maintain a high index of suspicion for COVID-19 infection in children and monitor for progression of illness, particularly among infants and children with underlying conditions. However, these findings must be interpreted with caution because of the high percentage of cases missing data on important characteristics. Because persons with asymptomatic and mild disease, including children, are likely playing a role in transmission and spread of COVID-19 in the community, social distancing and everyday preventive behaviors are recommended for persons of all ages to slow the spread of the virus, protect the health care system from being overloaded, and protect older adults and persons of any age with serious underlying medical conditions. Recommendations for reducing the spread of COVID-19 by staying at home and practicing strategies such as respiratory hygiene, wearing cloth face coverings when around others, and others are available on CDC’s coronavirus website at https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html. Summary What is already known about this topic? Data from China suggest that pediatric coronavirus disease 2019 (COVID-19) cases might be less severe than cases in adults and that children (persons aged <18 years) might experience different symptoms than adults. What is added by this report? In this preliminary description of pediatric U.S. COVID-19 cases, relatively few children with COVID-19 are hospitalized, and fewer children than adults experience fever, cough, or shortness of breath. Severe outcomes have been reported in children, including three deaths. What are the implications for public health practice? Pediatric COVID-19 patients might not have fever or cough. Social distancing and everyday preventive behaviors remain important for all age groups because patients with less serious illness and those without symptoms likely play an important role in disease transmission.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                8 September 2020
                September 2020
                8 September 2020
                : 3
                : 9
                : e2020495
                Affiliations
                [1 ]Office of Infection Control and Epidemiology, Children’s National Hospital, Washington, DC
                [2 ]Department of Pediatrics, George Washington University School of Health Science, Washington, DC
                [3 ]Department of Laboratory Medicine, Children’s National Hospital, Washington, DC
                [4 ]Division of Quality and Safety, Children’s National Hospital, Washington, DC
                [5 ]Chief Medical Office, Children’s National Hospital, Washington, DC
                [6 ]Division of Infectious Disease, Children’s National Hospital, Washington, DC
                Author notes
                Article Information
                Accepted for Publication: August 1, 2020.
                Published: September 8, 2020. doi:10.1001/jamanetworkopen.2020.20495
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Song X et al. JAMA Network Open.
                Corresponding Author: Xiaoyan Song, PhD, MBBS, CIC, Office of Infection Control and Epidemiology, Children’s National Hospital, 111 Michigan Ave, NW, Washington, DC 20010 ( xsong@ 123456cnmc.org ).
                Author Contributions: Dr Song had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Song, Delaney, Wessel, DeBiasi.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Song, DeBiasi.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Song.
                Administrative, technical, or material support: Delaney, Shah, Campos, DeBiasi.
                Supervision: Shah, Wessel, DeBiasi.
                Conflict of Interest Disclosures: None reported.
                Additional Contributions: Jeffrey Li, River Hill High School, Clarksville, Maryland, provided editing assistance and was not compensated for his help.
                Article
                zoi200709
                10.1001/jamanetworkopen.2020.20495
                7489826
                32897374
                2627e0ff-f964-4715-bd09-0627354102ff
                Copyright 2020 Song X et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 18 June 2020
                : 1 August 2020
                Categories
                Research
                Original Investigation
                Online Only
                Infectious Diseases

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