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. JAMA Network Open. 2020;3(9):e2020495. doi:10.1001/jamanetworkopen.2020.20495 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. Author affiliations and article information are listed at the end of this article. Open Access. This is an open access article distributed under the terms of the CC-BY License. JAMA Network Open. 2020;3(9):e2020495. doi:10.1001/jamanetworkopen.2020.20495 (Reprinted) September 8, 2020 1/8


Introduction
For many years, public health officials have anticipated the emergence of a highly contagious respiratory virus with pandemic potential. When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began circulating in late 2019, it was immediately compared with both seasonal and pandemic influenza virus given the common features shared by these viruses. Both SARS-COV-2 and influenza viruses have demonstrated their ease of person-to-person transmission through the respiratory droplet route. The diseases caused by these viruses also share similar clinical presentations, including fever and respiratory symptoms that range from mild forms, such as cough, to severe lung infections. 1,2 However, coronavirus disease 2019  has also demonstrated distinct clinical characteristics, such as anosmia and hypogeusia. 3,4 Although the search for a vaccine and a treatment continues for COVID-19, influenza has become detectable, vaccine preventable, and treatable.
Influenza in children has been well described and has been associated with serious complications including death. 5,6 In contrast, there has been a severe paucity of pediatric data with regard to COVID-19. Early and limited data suggested that children may be less likely to contract COVID-19, with fewer of them requiring hospitalization or experiencing fever, cough, or shortness of breath, compared with adult patients. 7,8 COVID-19-related pediatric death remains rare. 9 However, new and severe clinical manifestations associated with COVID-19 continue emerging, including a rare but severe illness termed multisystem inflammatory syndrome in children. 10 To date, little has been published directly comparing pediatric cohorts of patients with COVID-19 to those with seasonal influenza. In recognizing that prevention of COVID-19 may be further complicated during influenza season, when influenza and other respiratory viruses cocirculate in communities, we conducted this retrospective cohort study and compared children who were diagnosed with COVID-19, seasonal influenza A, and influenza B in a free-standing children's hospital in Washington, DC.

Patient Population and Study Setting
This cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children who were diagnosed with laboratory-confirmed seasonal influenza between October 1, 2019, and June 6, 2020, at Children's National Hospital in Washington, DC. Asymptomatic patients who tested positive for COVID-19 during preadmission or preprocedural screening were excluded from the study. The study was approved by the Children's National Hospital institutional research board. Owing to the retrospective nature of this study, a waiver of consent was granted by the institutional review board. This study followed the

Laboratory Testing
Testing for influenza A and B viruses was performed with 2 US Food and Drug Administration-cleared polymerase chain reaction assays: the Xpert Xpress Flu/RSV assay (Cepheid) and the ePlex Respiratory Pathogen Panel (GenMark Diagnostics). Testing for the SARS CoV2 was conducted using

Statistical Analysis
We performed descriptive analysis and calculated a percentage for categorical variables and a mean or median for continuous variables. We used an unadjusted logistic regression method and calculated odds ratios (ORs) to assess statistical associations between independent variables and COVID-19 vs seasonal influenza. Subanalyses were conducted by comparing patients with COVID-19 with those with influenza types A and B. A 2-sided P < .05 was considered statistically significant. The analysis was conducted using Stata (StataCorp LLC).    19,20 Further study is warranted to assess the potential benefits of interventions such as school closure on reducing disease burden and maintaining optimal operation of health care facilities.

Limitations
This study has limitations. Because it was a retrospective study, the findings are subject to biases owing to recall error or missing information that were introduced during a patient encounter. A single-center study also limited our ability to conduct subcohort analysis on patients who were admitted to the ICU because of an insufficient sample size and limited our ability to assess other risk factors, such as obesity. This study was also limited by differences in case ascertainment through positive test results because the 2 viruses were detected by different platforms.

Conclusions
This study found that patients with COVID-19 and those with seasonal influenza had similar hospitalization rates, ICU admission rates, and mechanical ventilator use. Compared with patients hospitalized with seasonal influenza, a greater proportion of patients hospitalized with COVID-19 had underlying medical conditions and reported fever, diarrhea or vomiting, headache, body ache or myalgia, or chest pain. As the COVID-19 pandemic continues and the 2020-2021 influenza season approaches, findings from our study may inform the prompt identification and treatment of children with a respiratory viral infection in health care facilities.

JAMA Network Open | Infectious Diseases
Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children