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Discover Pediatric Collections on COVID-19 and Racism and Its Effects on Pediatric Health

American Academy of Pediatrics
Article

Factors Associated With Severe SARS-CoV-2 Infection

Naïm Ouldali, David Dawei Yang, Fouad Madhi, Michael Levy, Jean Gaschignard, Irina Craiu, Tamazoust Guiddir, Cyril Schweitzer, Arnaud Wiedemann, Mathie Lorrot, Anne-Sophie Romain, Aurélie Garraffo, Hervé Haas, Sébastien Rouget, Loïc de Pontual, Camille Aupiais, Alain Martinot, Julie Toubiana, Laurent Dupic, Philippe Minodier, Manon Passard, Alexandre Belot, Corinne Levy, Stephane Béchet, Camille Jung, Mayssa Sarakbi, Sarah Ducrocq, Nevena Danekova, Imen Jhaouat, Olivier Vignaud, Nathalie Garrec, Elisabeth Caron, Robert Cohen, Vincent Gajdos, François Angoulvant and on behalf of the investigator group of the PANDOR study
Pediatrics March 2021, 147 (3) e2020023432; DOI: https://doi.org/10.1542/peds.2020-023432
Naïm Ouldali
aDepartment of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Université de Paris, Paris, France;
bAssociation Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France;
cUniversité de Paris, Institut National de la Santé et de la Recherche Médicale UMR 1123, ECEVE, Paris, France;
dFrench Pediatric Infectious Disease Group, Paris, France;
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David Dawei Yang
ePediatric Emergency Department, Assistance Publique - Hôpitaux de Paris, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France;
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Fouad Madhi
dFrench Pediatric Infectious Disease Group, Paris, France;
fPediatric Department, Centre Hospitalier Intercommunal,
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Michael Levy
gPediatric ICU, Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Université de Paris, Paris, France;
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Jean Gaschignard
aDepartment of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Université de Paris, Paris, France;
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Irina Craiu
hPediatric Emergency Department, Assistance Publique - Hôpitaux de Paris, Bicêtre University Hospital, Université de Paris Saclay, Le Kremlin-Bicêtre, France;
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Tamazoust Guiddir
hPediatric Emergency Department, Assistance Publique - Hôpitaux de Paris, Bicêtre University Hospital, Université de Paris Saclay, Le Kremlin-Bicêtre, France;
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Cyril Schweitzer
iPediatric Department, Children’s Hospital, University Hospital of Nancy, Université de Lorraine, Vandoeuvre les Nancy, France;
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Arnaud Wiedemann
iPediatric Department, Children’s Hospital, University Hospital of Nancy, Université de Lorraine, Vandoeuvre les Nancy, France;
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Mathie Lorrot
jDepartment of General Pediatric, Assistance Publique - Hôpitaux de Paris, Armand Trousseau University Hospital, Sorbonne Université, Paris, France;
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Anne-Sophie Romain
jDepartment of General Pediatric, Assistance Publique - Hôpitaux de Paris, Armand Trousseau University Hospital, Sorbonne Université, Paris, France;
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Aurélie Garraffo
kDepartment of Pediatrics, Centre Hospitalier Intercommunal de Villeneuve Saint-Georges, Villeneuve Saint-Georges, France;
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Hervé Haas
lPediatric Emergency Department, Hôpitaux pédiatriques de Nice CHU-Lenval, Nice, France;
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Sébastien Rouget
mPediatric Department, Centre Hospitalier Sud-Francilien, Corbeil, France;
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Loïc de Pontual
nPediatric Emergency Departement, Assistance Publique-Hôpitaux de Paris - General Pediatric, Jean Verdier University Hospital, Bondy, France;
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Camille Aupiais
nPediatric Emergency Departement, Assistance Publique-Hôpitaux de Paris - General Pediatric, Jean Verdier University Hospital, Bondy, France;
oInstitut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, UMRS 1138, Sorbonne Université, Université de Paris, Paris, France;
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Alain Martinot
pPediatric Emergency Unit and Infectious Diseases, Centre Hospitalier Universitaire Lille, Université de Lille, Lille, France;
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Julie Toubiana
qDepartment of General Pediatrics and Pediatric Infectious Diseases, Assistance Publique – Hôpitaux de Paris, Necker-Enfants-Malades University Hospital, Université de Paris, & Institut Pasteur, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France;
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Laurent Dupic
rPediatric ICU, Assistance Publique-Hôpitaux de Paris, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France;
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Philippe Minodier
sPediatric Emergency Department, Assistance Publique - Hôpitaux de Marseille, Marseille Nord University Hospital, Marseille, France;
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Manon Passard
tPediatric Emergency Department, Hospices Civils de Lyon, Hopital Femme, Mère Enfant, Bron, France;
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Alexandre Belot
uPediatric Nephrology, Rheumatology, Dermatology, Hospices Civils de Lyon, Hopital Femme, Mère Enfant, & Centre International de Recherche en Infectiologie/Institut National de la Santé et de la Recherche Médicale U1111, Bron, France;
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Corinne Levy
bAssociation Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France;
dFrench Pediatric Infectious Disease Group, Paris, France;
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Stephane Béchet
bAssociation Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France;
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Camille Jung
vCentre Hospitalier Intercommunal, Clinical Research Center, and
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Mayssa Sarakbi
wDepartment of Pediatrics, Centre Hospitalier Intercommunal de Gonesse, Gonesse, France;
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Sarah Ducrocq
xDepartment of Pediatrics, Centre hospitalier de Longjumeau, Longjumeau, France;
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Nevena Danekova
yPediatric Emergency Departement, Assistance Publique - Hôpitaux de Paris, Louis Mourier University Hospital, Colombes, France;
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Imen Jhaouat
zDepartment of Pediatrics, Centre hospitalier d’Orléans, Orléans, France;
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Olivier Vignaud
aaDepartment of Pediatrics, Grand Hôpital de l'Est Francilien, Meaux, France;
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Nathalie Garrec
bbDepartment of Pediatrics, Grand Hôpital de l'Est Francilien, Marnes la vallée, France;
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Elisabeth Caron
ccDepartment of Pediatrics, Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye, Poissy, France;
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Robert Cohen
bAssociation Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France;
dFrench Pediatric Infectious Disease Group, Paris, France;
ddNeonates Department, Centre Hospitalier Intercommunal, Université Paris Est, IMRB-GRC GEMINI, Créteil, France;
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Vincent Gajdos
eePediatric Department, Assistance Publique - Hôpitaux de Paris, Antoine Béclère University hospital, Université de Paris Saclay, Clamart, France; and
ffCentre for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale UMR1018, Villejuif, France
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François Angoulvant
dFrench Pediatric Infectious Disease Group, Paris, France;
ePediatric Emergency Department, Assistance Publique - Hôpitaux de Paris, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France;
oInstitut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, UMRS 1138, Sorbonne Université, Université de Paris, Paris, France;
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Abstract

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution.

METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement.

RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1–10.3), hypoxemia (OR = 8.9 [2.6–29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4–27.5]).

CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.

  • Abbreviations:
    CI —
    confidence interval
    CRP —
    C-reactive protein level
    CT —
    computed tomography
    IQR —
    interquartile range
    LRTI —
    lower respiratory tract infection
    MIS-C —
    multisystem inflammatory syndrome in children
    OR —
    odds ratio
    RT-PCR —
    real-time reverse transcriptase polymerase chain reaction
  • What’s Known on This Subject:

    Authors of preliminary reports on pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection suggested that very young age and comorbidities may increase the risk of severe evolution. The role of these conditions remains to be elucidated by additional studies.

    What This Study Adds:

    We conducted a national hospital-based surveillance of SARS-CoV-2 infection from February to June 2020. By contrast with initial reports, children <90 days accounted for a large part of admitted children but were at the lowest risk of severe SARS-CoV-2 disease.

    Infection with the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease (COVID-19), emerged in late 2019 in China and has led to a major pandemic.1 As of June 2020, it was responsible for >400 000 deaths worldwide.2 France is among the most affected countries with 30 000 deaths reported to date.2

    In epidemiological reports, children were underrepresented in severe cases, accounting for ∼1% to 2% of hospitalized COVID-19.3 This finding has been supported by researchers in several studies suggesting both a lower rate of infection in children than in adults4,5 and a high proportion of benign forms among infected children.6–8 However, severe disease evolution requiring intensive care can occur.9,10 Furthermore, recently, severe pediatric inflammatory forms with hemodynamic failure have been described.11–16 In this context, identifying these severe forms early among children infected by SARS-CoV-2 is critical.

    Reports of SARS-CoV-2 infections in children suggested that children <1 year old and children with comorbidities may be at higher risk of severe disease evolution.2,17 However, these studies were mainly focused on respiratory forms and did not cover the broad clinical spectrum of SARS-CoV-2 infections in children. Thus, factors associated with severe SARS-CoV-2 infection in children remain to be elucidated.

    Because of the relative rarity of severe COVID-19 in children, an accurate description of the spectrum of severe COVID-19 in children requires wide-scale studies, with precise description of clinical features and outcomes, which are challenging to set up in the context of health care resources under high pressure. Thus, a few studies provided a description of these pediatric severe forms at a country level. Sparse information is available about factors associated with severe disease progression in children.18 In France, we took advantage of a previously established national network of pediatric hospital surveilling bacterial meningitis for 20 years19,20 to extend this system to children hospitalized with SARS-CoV-2 infection.

    The aim with this national surveillance was to provide precise information on the clinical spectrum of hospitalized pediatric COVID-19, rate of severe forms, and predictors of severe disease progression.

    Methods

    We conducted a national prospective surveillance of children hospitalized with SARS-CoV-2 infection. The study was approved by the Institut National de la Santé et de la Recherche Médicale ethics committee for evaluation, the institutional review board (IRB00003888), and was registered at ClinicalTrials.gov (NCT04336956).

    Patients and Settings

    We recruited 60 hospitals throughout France for this study, using the French pediatric bacterial meningitis network.19,20 We included all pediatric patients with SARS-CoV-2 infection who were hospitalized in one of these centers from February 15 to June 1, 2020. Confirmed SARS-CoV-2 infection was defined by a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for SARS-CoV-2 on a nasopharyngeal swab and computed tomography (CT) scan–based cases were defined by characteristic chest CT scan lesions according to European Centre for Disease Prevention and Control and French National Health Agency case definition.21 Radiologic evidence of lesions compatible with COVID-19 were unilateral or bilateral subpleural ground-glass opacities and consolidations, although other etiologies can cause ground-glass opacities on CT, including vaping and interstitial lung infections.22,23 A CT scan was used to define the site of disease and/or in a few cases the presence of the infection. During the same period, Public Health France, the national French public health agency, counted all hospitalized pediatric SARS-CoV-2 infections cases in France, which allowed for estimating the completeness of our surveillance system. Similar to our surveillance system, the definition of cases counted by Public Health France included a positive RT-PCR result for SARS-CoV-2 or a characteristic chest CT scan lesions.24

    For each patient, an electronic case report form was prospectively completed on a secure database, and the following data were recorded: demographic characteristics, comorbidities, initial symptoms and clinical signs, biological and microbiologic parameters, radiography findings, treatments, and course during hospitalization.

    Outcome Measure

    The main outcome was the proportion of severe disease evolution among all included children with a SARS-CoV-2 infection, defined by the need for either ventilatory or hemodynamic support during hospitalization, or death.17 Ventilatory support was defined by use of noninvasive ventilation, including high-flow oxygen via nasal cannula, continuous positive airway pressure, and bilevel positive airway pressure or the use of invasive ventilation. We assessed demographic, clinical, and biological factors associated with severe disease progression in children at the acute phase of the SARS-CoV-2 infection. For biological factors, we considered explorations performed at admission. Hypoxemia was defined by oxygen saturation <95%.25 Thrombocytopenia was defined by platelet count <150 g/L.

    Secondary outcomes were rate of severe disease by clinical presentation, comorbidities, and age groups (<90 days, 90 days to <1 year, 1 to <5, 5 to <10, 10 to <15, and 15 to <18 years). Among comorbidities, obesity was defined by a BMI >25 and overweight by a weight >+2 SDs for age and sex on the basis of national weight curves and/or a BMI >25.26

    Statistical Analysis

    We described patient characteristics with numbers (percentages) for categorical variables and median (interquartile range [IQR]) for quantitative variables. We assessed the association between these characteristics and severe disease evolution by Fisher’s exact test for categorical variables and the Mann–Whitney U test for quantitative variables. We then used a multivariate logistic regression model with the backward stepwise method to identify factors independently associated with disease severity, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Variables significant at P ≤.20 on univariate analyses were included in the stepwise selection. Quantitative variables associated with severity were transformed into binary variables by using the receiver operating characteristic curve analysis. A 2-sided P value <.05 was considered statistically significant. All statistical analyses involved using R v3.6.1 (http://www.R-project.org).

    Results

    Since February 15, 2020, 397 hospitalized children were included in the study: 385 had a positive RT-PCR nasopharyngeal test result for SARS-CoV-2, and 12 were CT scan based with radiologic evidence of lesions compatible with COVID-19; see flowchart (Supplemental Fig 3). On the basis of systematic mandatory reporting of any children hospitalized with SARS-CoV-2 infection via Public Health France (1032 cases over the same period), the completeness of our surveillance system was 38.5% (95% CI: 35.5–41.5).

    The weekly number of children admitted to hospital with SARS-CoV-2 infection peaked during March 23 to 30, 2020 (ie, 1 week after the national lockdown), and strongly decreased thereafter (Fig 1). This number mirrored the evolution of adults admitted with SARS-CoV-2 infection over the same period in France (http://www.santepubliquefrance.fr). The geographic distribution of cases is displayed in Supplemental Fig 4.

    FIGURE 1
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    FIGURE 1

    Evolution of weekly admission of children with SARS-CoV-2 infection, N = 397. The vertical arrow shows the national lockdown which started on March 17, 2020. Adult data are from Public Health France (N = 97 406).38

    Patients Characteristics and Clinical Patterns

    The clinical characteristics of children are in Table 1. The median age was 16 months (IQR, 51 days–134 months). Overall, 114 (29%) children had comorbidities, mainly chronic respiratory disease (such as asthma, cystic fibrosis, and bronchopulmonary dysplasia), immunosuppression or malignancy, neurologic disorders, and sickle cell disease (Table 1). The main symptoms were fever (n = 300 of 385, 78%), cough (n = 168 of 391, 43%), feeding difficulties (n = 152 of 385, 39%), shortness of breath or dyspnea (n = 119 of 390, 31%), and diarrhea (n = 93 of 392, 24%).

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    TABLE 1

    General Characteristics of the Children Hospitalized With SARS-CoV-2 Infection in France, February 15 to June 1, 2020 (N = 397)

    Among the 397 children included, levels of inflammatory parameters were low for most children (median C-reactive protein level [CRP], 5 mg/L [IQR, 2–36], procalcitonin level, 0.15 ng/mL [IQR, 0.1–0.37], neutrophil count, 3.8 g/L [IQR, 2.1–7.1]). A total of 80 of 301 (27%) cases showed lymphopenia and 28 of 313 (9%) showed thrombocytopenia.

    Chest radiography findings were abnormal in 70 of 203 (34%) children, with bilateral interstitial infiltrate as the most-frequent lesion (Table 1).

    A posteriori and on the basis of the final diagnosis recorded by the physicians and hospital treatments, we distinguished 4 different clinical patterns:

    • Pattern 1: paucisymptomatic SARS-CoV-2 infection with no hospital treatment required, admitted for clinical surveillance (n = 148, 37%). Three of these paucisymptomatic children were admitted in February in a PICU to be isolated according to local guidelines, without any other criteria of intensive care requirement.

    • Pattern 2: SARS-CoV-2 infection requiring hospital care (n = 158 cases, 40%), with 3 main forms of COVID-19 described: (1) lower respiratory tract infection (LRTI) (n = 95 of 158, 60%), (2) digestive form (n = 24 of 158, 15%), and (3) isolated fever (n = 28 of 158, 18%). We classified children according to the physicians’ clinical assessment describing the severity of each organ involvement (oxygenotherapy requirement, intravenous rehydration, etc). Physicians also defined a primary diagnosis, which allowed for classification in the respiratory or digestive form. Other forms (n = 11 of 158, 7%) are detailed in Supplemental Table 5.

    • Pattern 3: multisystem inflammatory syndrome in children (MIS-C) was defined by persistent fever, presence of laboratory markers of inflammation, manifestation of signs or symptoms of organ dysfunction, lacking an alternative diagnosis,27 and, as for the other patients included in this cohort, a positive RT-PCR nasopharyngeal result for SARS-CoV-2 (MIS-C, n = 29, 7%).

    • Pattern 4: hospitalization for another disease and COVID-19 was not the final diagnosis (n = 62 cases, 16%). Some of these were admitted children tested for COVID-19 as part of hospital-wide surveillance. The most frequent diagnoses were surgical pathology and urinary tract infection. Each diagnosis is detailed in Supplemental Table 6.

    Both the clinical pattern of SARS-CoV-2 infection and the rate of severity were highly different depending on age group (Table 2, Fig 2). Children <90 days of age were the largest group, with 145 patients (37%) of our cohort. Their clinical pattern was specific because most them (59%, 85 of 145) were paucisymptomatic, no MIS-C were observed, and LRTI were diagnosed in 18 cases (12%). In this age group, fever was almost a constant finding (92%). Overall, 4 (3%) children <90 days had a severe disease. Among children <90 days old, 63 of 145 (43%) were <30 days old, among which severe disease was observed in 3 of 63 (5%) cases, including 2 LRTI and 1 other diagnosis: prematurity and Escherichia coli meningitis. In comparison, children between 3 and 12 months old were paucisymptomatic in only 33% (16 of 48) cases, as many as were diagnosed with LRTI (16 of 48). However, patients with severe diseases remained rare, with 3 of 48 cases (6%), and only 1 patient was diagnosed as MIS-C. LRTI was a major diagnosis in all age groups beyond 1 year with 20% to 36% of cases according to age group.

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    TABLE 2

    Characteristics and Evolution by Age Group

    FIGURE 2
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    FIGURE 2

    Clinical pattern by age group, N = 397. LRTI, low respiratory tract infection; MIS-C, pediatric inflammatory multisystem syndrome

    The number of patients with MIS-C increased in older children age between 1 and 5 years old, 5 to 10 years old, and 10 to 15 years old, with 7 of 46 cases (15%), 9 of 49 cases (18%), and 10 of 65 cases (15%), respectively, but decreased for children age between 15 and 18 years old (only 2 of 44 [5%] MIS-C cases). Antibiotics were the most-used treatment, with a percentage varying from 31% to 65% according to age group. Among children <90 days of age, 40% received antibiotics, despite most of them being paucisymptomatic.

    The characteristics described by clinical patterns are provided in Supplemental Table 7, which clearly show a specific pattern for the 29 children diagnosed as MIS-C with high and persistent fever, higher inflammatory syndrome with a median CRP at 179 (105–270), high proportion of severe disease (52%), and a long delay between COVID-19 contact and hospitalization (34 days, IQR: 23–47).

    Factors Associated With Severe Disease Excluding Patients with MIS-C

    Factors associated with disease severity were assessed for pattern 1 and 2 children because pattern 3 (MIS-C) was not considered an acute SARS-CoV-2 infection and showed a specific profile, and outcomes from children in pattern 4 were not mainly related to SARS-CoV-2 infection. Overall, severe disease was detected in 23 of 306 children (11%, 95% CI: 8%–15%), including 20 patients requiring ventilatory support and 5 with hemodynamic support (Table 3). Numerous characteristics were associated with disease severity on univariate analysis (Table 3), but only 3 were independently associated on multivariate analysis: age ≥10 years (OR: 3.4, 95% CI: 1.1–10.3, P = .034), hypoxemia (OR: 8.9, 95% CI: 2.6–29.7, P = .0004), and CRP ≥80 mg/L (OR: 6.6, 95% CI: 1.4–27.5, P = .012).

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    TABLE 3

    Factors Associated With Severe Form of SARS-CoV-2 Infection

    Deaths

    We recorded 6 deaths in our surveillance system, plus 1 patient positive for immunoglobulin G anti–SARS-CoV-2 antibody who was enrolled but not included in the main analysis because the case did not meet our inclusion criteria (negative on RT-PCR nasopharyngeal test) (Supplemental Fig 3). These 7 patients were the only deaths reported in children to Public Health France in the context of SARS-CoV-2 infection in France, and some were previously reported.28 Among these 7 children, 3 had a comorbidity (immunodeficiency, leukemia, and encephalopathy). Most had a respiratory failure, with high levels of inflammatory parameters, and the imputability of SARS-CoV-2 infection in the death was high in 5 cases (Table 4).

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    TABLE 4

    Characteristics of the 7 Children Who Died in a Context of SARS-CoV-2 Infection

    Discussion

    This national prospective study has allowed for analyzing the clinical spectrum of hospitalized SARS-CoV-2 infection in children, including acute infections and MIS-C, and assessing factors associated with severe clinical evolution. A total of 60 hospitals throughout France participated, which allowed us to obtain a completeness rate of 38.5%. The evolution of pediatric cases over time mirrored that of adult admission reported by Public Health France both temporally and geographically, which suggests that our network adequately captured the epidemiological pattern of hospitalized children with SARS-CoV-2 infections. The strong decrease in cases 2 weeks after the national lockdown highlighted the major impact of these unprecedented measures in reducing the burden of SARS-CoV-2 infection in children.

    An important concern in the literature was the specific burden of SARS-CoV-2 infection in young children.6,29,30 Authors of a report from China6 described a higher rate of severe forms among children aged <1 year versus older children, and authors of another report from Italy suggest that infants aged <6 months seem significantly more susceptible to severe forms of the disease, leading to important concerns about this specific age group6,29,30 and playing a role in recommending closure of most day care centers during lockdown in France. Our results shed particular light on this issue. On the one hand, children <90 days old were the leading group because they accounted for 37% of all children hospitalized, but on the other, 97% (141 of 145) of them had no severe disease and 68% were discharged from the hospital with little care. Fever was the most common symptom (92%, 128 of 139) in this age group, and 40% (58 of 145) received antibiotics. In another words, most of these children were hospitalized owing to risk of bacterial infection because they had fever without a clear source and were <90 days old.31 The use of a rapid test at the bedside to identify SARS-CoV-2 would be helpful to improve the care of these children in pediatric emergency departments.

    In a recent study, Götzinger et al32 also suggested that the likelihood of severe forms may be increased in children <1 month old. However, our findings suggest that the rate of severe forms was lowest in very young children and highest for children ≥10 years on both univariate and multivariate analysis. These findings agree with Zachariah et al,17 who describe the disease course with COVID-19 in 14 children <1 year old, with no case of severe evolution.

    The definition of severity should be considered in these comparisons. Although we defined severity as need for ventilatory or hemodynamic support, in line with Zachariah et al,17 Dong et al,6 who described the Chinese cohort, defined severe cases as respiratory symptoms, dyspnea, and hypoxemia,6 and Götzinger et al32 defined severe cases as admission to the PICU. In our cohort, several children <1 year old required transient nasal oxygenotherapy, and several were transferred to the PICU only for surveillance with regards to the very young age, depending on local practices. They evolved favorably in the large majority of cases, without ventilatory support, and have not been considered as severe cases. This information could be useful to guide reopening day care centers and recommend suitable mitigation measures, which are highly difficult to apply in these settings. According to the French Pediatric Society, the educational and social benefits provided by school far outweigh the risks of a possible COVID-19 contamination of children in school environments or in day care centers.33

    We also identified several factors associated with severe disease evolution, including hypoxemia and CRP ≥80 mg/L. Few studies assessed factors associated with poor outcomes in pediatric COVID-19. The 2 main studies are a recent US monocentric cohort17 and a multinational study.32 Elevated levels of inflammatory parameters and respiratory symptoms were also found as a prognostic factor.34

    This surveillance system allowed us to identify different clinical profiles of hospitalized children with SARS-CoV-2 infections, ranging from paucisymptomatic forms to MIS-C. The main clinical symptoms reported in our cohort agreed with the literature (fever in 70%–80%, cough in 40%–50%, dyspnea in 30%–40%).7,17 Among this wide clinical spectrum, the proportion of severe forms was highly variable and greatest for LRTI (21%) and MIS-C (52%). This novel clinical entity has since been widely described in Italy,11 France,12,13 England,15 and the United Sates,14,16 reporting a high rate of PICU transfer (60%–75%) and hemodynamic support requirement (40%–50%).11,12,15 Our findings confirm that MIS-C is among the most severe forms linked to SARS-CoV-2 infection in children. Our results are in line with previous studies suggesting that MIS-C happens not in the acute phase of the SARS-CoV-2 infection but as a postinfectious phenomenon despite our patients expressing a positive RT-PCR result.

    Another issue of concern at the time of school reopening is children with comorbidities, including immunosuppression. Several comorbidities have been associated with poor outcomes in adults,35 including chronic respiratory and cardiac diseases, but these remain unclear for children.7,18,28,36,37 Comorbidities were frequent in our cohort (29%, n = 114), but these comorbidities were not independently associated with severe evolution and accounted for only 22 severe cases of hospitalization on a national scale. These observations may also help policy makers allow for standard school activities for these populations and help physicians to reassure families in this process.

    The main strength of our study was the use of a national surveillance system that captured a large part of hospitalized cases of SARS-CoV-2 infections with precise clinico-biological data in France, allowing us to define the rate of severe disease evolution by clinical pattern and factors associated with severe evolution. Our study also has several limitations. First, we decided to include only children with a positive RT-PCR nasopharyngeal result for SARS-CoV-2 or a CT scan revealing radiographic evidence of lesions compatible with COVID-19 and excluded children with positive serology alone. These criteria allowed us to enhance the imputability of SARS-CoV-2 infection in the clinical features observed but may have led to missing some patients with postinfectious disorders such as MIS-C, for which the RT-PCR nasopharyngeal test result may be negative.11,13 Further studies including MIS-C with negative RT-PCR nasopharyngeal results for SARS-CoV-2 but positive serology are ongoing to appreciate this burden. Second, the clinical spectrum of included patients may depend on the SARS-CoV-2 testing strategy. At the early stage of the epidemic, only patients with respiratory symptoms were tested, and indications became broader when asymptomatic, digestive, and inflammatory forms had been described, which led some hospitals to adopt universal testing at admission.17 Thus, the proportion of the different forms was likely be influenced by evolving local SARS-CoV-2 testing strategies, and the children in pattern 4 (positive for SARS-CoV-2 but hospitalized for another disease) may be overestimated. However, most of the PICUs throughout France followed the same testing policy, with wide indications for any child requiring PICU admission.

    Conclusions

    This national surveillance system allowed for describing the broad clinical spectrum of children hospitalized with acute SARS-CoV-2 infections and defining the risk of severe disease for each clinical form. Infants <3 months old were the main age group requiring hospitalization, but most of them expressed a mild form of COVID-19. The independent factors associated with increased risk of severe disease may help clinicians manage this infection in children.

    Acknowledgments

    In addition to the authors, the following investigators participated in the PANDOR study: Anxionnat Raphaël, Auburtin Brigitte, Azemar Benjamin, Barrey Catherine, Belgaid Abdelmalek, Benkaddouss Sakina, Benoist Grégoire, Bensaid Philippe, Biran Valérie, Bordet Jeanne, Blanc Philippe, Bost-Bru Cécile, Boussicault Gérald, Brehin Camille, Brouard Jacques, Cantais Aymeric, Casha Paul, Caurier Bernard, Charbonnier Lorelei, Charreton Claire, Chenel Claude, Chognot Didier, Cohen Laure, Dabbagh Dana, De Feraudy Yvan, Delestrain Céline, Dessioux Emmanuelle, Do-Cao Jéremy, Dommergues Marie-Aliette, Drouard Anne, Dubos François, Dupré Charlène, Durrmeyer Xavier, Elmerich Florence, Enchery Sophie, Fruscione Sophie, Girard Florent, Gouraud François, Gruss Richard, Guerder Margaux, Guglielmino Patricia, Hentgen Véronique, Hoeusler Valentine, Huet Fréderic, Idier Charlotte, Jany Bérangère, Javouhey Etienne, Kalach Nicolas, Kom Rémi, Kutsia Ekaterina, Larakeb Anis, Latry Vanessa, Le Stradic Camille, Leboucher Bertrand, Lemaire-Weber Aurélie, Lepage Jean-Marie, Leteurtre Stéphane, Loeile Camille, Louf Sylvie, Maakaroun-Vermesse Zoha, Mandelcwajg Alexis, Marin Mariana, Marques Cécilia, Martha Sandrine-Anne, Martinat Laurence, Masserot Caroline, Mathivon Laurence, Meslin Pauline, Mestre Nathalie, Milcent Karen, Mizzi-Rozier Marie, Monceaux Françoise, Monfort Marie, Mougenot Emmanuelle, Moulène Eric, Florence Moulin, Nattes Elodie, Odorico Sophie, Orcel Marie-Clothilde, Oualha Medhi, Ouziel Antoine, Peigne Chantal, Pellegrino Béatrice, Petit Isabelle, Pinquier Didier, Pons Charlotte, Rabier Valérie, Robert Blandine, Roche Christine, Roullaud Sylvie, Roybet Danielle, Rozental Jonathan, Sanchez Stéphane, Schneider Jean-Marc, Soto Bertrand, Szulc Marie, Thach Caroline, Thevenet Léa, Tran Antoine, Ursulescu Nicoleta, Valentin Cécile, Verney Cindy, Vignaud Olivier, Walser Sébastien, Yangui Mohamed-Amine, Zimmermann Brigitte.

    We thank our clinical research assistants: Bommenel Tchadie, Bouquignaud Christelle, Bouvy Emilie, Fleury Marjory, Kara Sofia, Khalil Mirna, Madpathage Senanayake Videsheka, Vassal Mélanie, Vasseur Valérie. We are grateful to Isabelle Ramay, Claire Prieur, Marine Borg, Aurore Prieur, Laura Meyet and Jéremy Levy from ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France. We are grateful to Cecile Hoffart, Maxime Brussieux from Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France. We are grateful to Denise Antona, Public Health France. We are grateful to Pauline Scherdel and Pr Martin Chalumeau, Inserm UMR 1153. We are grateful to Pr David Skurnik, INSERM U1151-Equipe 11. We are grateful to every and each microbiologic laboratory staff who performed SARS-COV2 RT-PCR in each center.

    Footnotes

      • Accepted December 9, 2020.
    • Address correspondence to François Angoulvant, MD, PhD, Pediatric Emergency Department, Necker-Enfants Malades University Hospital, 149 Rue de Sèvre, 75015 Paris, France. E-mail: francois.angoulvant{at}aphp.fr
    • A complete list of group members appears in the Acknowledgments.

    • This trial has been registered at www.clinicaltrials.gov (identifier NCT04336956).

    • Deidentified participant data may be available on reasonable request by sending an e-mail to francois.angoulvant{at}aphp.fr.

    • FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

    • FUNDING: Association Clinique et Thérapeutique Infantile du Val de Marne and the Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France.

    • POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

    References

    1. ↵
      1. Zhu N,
      2. Zhang D,
      3. Wang W, et al.; China Novel Coronavirus Investigating and Research Team
      . A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733
      OpenUrlCrossRefPubMed
    2. ↵
      1. Dong E,
      2. Du H,
      3. Gardner L
      . An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20(5):533–534
      OpenUrlCrossRefPubMed
    3. ↵
      1. Wu Z,
      2. McGoogan JM
      . Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239–1242
      OpenUrlCrossRefPubMed
    4. ↵
      1. Gudbjartsson DF,
      2. Helgason A,
      3. Jonsson H, et al
      . Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med. 2020;382(24):2302–2315
      OpenUrlCrossRefPubMed
    5. ↵
      1. Levy C,
      2. Basmaci R,
      3. Bensaid P, et al
      . Changes in RT-PCR-positive SARS-CoV-2 rates in adults and children according to the epidemic stages. medRxiv. Preprint posted online June 9, 2020. doi:10.1101/2020.05.18.20098863
    6. ↵
      1. Dong Y,
      2. Mo X,
      3. Hu Y, et al
      . Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145(6):e20200702
      OpenUrlAbstract/FREE Full Text
    7. ↵
      1. Castagnoli R,
      2. Votto M,
      3. Licari A, et al
      . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174(9):882–889
      OpenUrl
    8. ↵
      1. Lu X,
      2. Zhang L,
      3. Du H, et al.; Chinese Pediatric Novel Coronavirus Study Team
      . SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663–1665
      OpenUrlCrossRefPubMed
    9. ↵
      1. Shekerdemian LS,
      2. Mahmood NR,
      3. Wolfe KK, et al.; International COVID-19 PICU Collaborative
      . Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA Pediatr. 2020;174(9):868–873
      OpenUrlPubMed
    10. ↵
      1. Tagarro A,
      2. Epalza C,
      3. Santos M, et al
      . Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain [published online ahead of print April 8, 2020]. JAMA Pediatr. doi:10.1001/jamapediatrics.2020.1346
    11. ↵
      1. Verdoni L,
      2. Mazza A,
      3. Gervasoni A, et al
      . An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771–1778
      OpenUrlCrossRefPubMed
    12. ↵
      1. Toubiana J,
      2. Poirault C,
      3. Corsia A, et al
      . Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020;369:m2094
      OpenUrlAbstract/FREE Full Text
    13. ↵
      1. Pouletty M,
      2. Borocco C,
      3. Ouldali N, et al
      . Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis. 2020;79(8):999–1006
      OpenUrlAbstract/FREE Full Text
    14. ↵
      1. Cheung EW,
      2. Zachariah P,
      3. Gorelik M, et al
      . Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. JAMA. 2020;324(3):294–296
      OpenUrlCrossRefPubMed
    15. ↵
      1. Whittaker E,
      2. Bamford A,
      3. Kenny J, et al.; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia
      . Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020;324(3):259–269
      OpenUrlCrossRefPubMed
    16. ↵
      1. Feldstein LR,
      2. Rose EB,
      3. Horwitz SM, et al
      . Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334–346
      OpenUrlCrossRefPubMed
    17. ↵
      1. Zachariah P,
      2. Johnson CL,
      3. Halabi KC, et al
      . Epidemiology, clinical features, and disease severity in patients with coronavirus disease 2019 (COVID-19) in a Children’s Hospital in New York City, New York. JAMA Pediatr. 2020;174(10):e202430
      OpenUrl
    18. ↵
      1. Mehta NS,
      2. Mytton OT,
      3. Mullins EWS, et al
      . SARS-CoV-2 (COVID-19): what do we know about children? A systematic review. Clin Infect Dis. 2020;71(9):2469–2479
      OpenUrl
    19. ↵
      1. Levy C,
      2. Vie le Sage F,
      3. Varon E,
      4. Chalumeau M,
      5. Grimprel E,
      6. Cohen R
      . Pediatric ambulatory and hospital networks for surveillance and clinical epidemiology of community-acquired infections. J Pediatr. 2018;194:269–270.e2
      OpenUrlPubMed
    20. ↵
      1. Ouldali N,
      2. Levy C,
      3. Varon E, et al.; French Pediatric Meningitis Network
      . Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis. 2018;18(9):983–991
      OpenUrlCrossRefPubMed
    21. ↵
      European Centre for Disease Prevention and Control. Case definition for coronavirus disease 2019 (COVID-19), as of May 29, 2020. Available at: https://www.ecdc.europa.eu/en/covid-19/surveillance/case-definition. Accessed July 7, 2020
    22. ↵
      1. Shi H,
      2. Han X,
      3. Jiang N, et al
      . Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20(4):425–434
      OpenUrlPubMed
    23. ↵
      1. Xia W,
      2. Shao J,
      3. Guo Y,
      4. Peng X,
      5. Li Z,
      6. Hu D
      . Clinical and CT features in pediatric patients with COVID-19 infection: different points from adults. Pediatr Pulmonol. 2020;55(5):1169–1174
      OpenUrlCrossRefPubMed
    24. ↵
      1. Public Health France
      . Définition de Cas D’infection Au SARS-CoV-2. Saint-Maurice, France: Santé Publique France; 2020
    25. ↵
      1. Shah SN,
      2. Bachur RG,
      3. Simel DL,
      4. Neuman MI
      . Does this child have pneumonia?: the rational clinical examination systematic review. JAMA. 2017;318(5):462–471
      OpenUrlPubMed
    26. ↵
      1. Heude B,
      2. Scherdel P,
      3. Werner A, et al
      . A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts. Lancet Digit Health. 2019;1(8):e413–e423
      OpenUrl
    27. ↵
      World Health Organization. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Available at: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19. Accessed August 27, 2020
    28. ↵
      1. Oualha M,
      2. Bendavid M,
      3. Berteloot L, et al
      . Severe and fatal forms of COVID-19 in children. Arch Pediatr. 2020;27(5):235–238
      OpenUrlPubMed
    29. ↵
      1. Swann OV,
      2. Holden KA,
      3. Turtle L, et al.; ISARIC4C Investigators
      . Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ. 2020;370:m3249
      OpenUrlAbstract/FREE Full Text
    30. ↵
      1. Parri N,
      2. Magistà AM,
      3. Marchetti F, et al.; CONFIDENCE and COVID-19 Italian Pediatric Study Networks
      . Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks. Eur J Pediatr. 2020;179(8):1315–1323
      OpenUrlCrossRef
    31. ↵
      1. Gomez B,
      2. Mintegi S,
      3. Bressan S,
      4. Da Dalt L,
      5. Gervaix A,
      6. Lacroix L; European Group for Validation of the Step-by-Step Approach
      . Validation of the “step-by-step” approach in the management of young febrile infants. Pediatrics. 2016;138(2):e20154381
      OpenUrlAbstract/FREE Full Text
    32. ↵
      1. Götzinger F,
      2. Santiago-García B,
      3. Noguera-Julián A, et al.; ptbnet COVID-19 Study Group
      . COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4(9):653–661
      OpenUrlCrossRefPubMed
    33. ↵
      1. Cohen R,
      2. Delacourt C,
      3. Gras-Le Guen C,
      4. Launay E; French Pediatric Society; Guidelines of the French Pediatric Society
      . COVID-19 and schools. Arch Pediatr. 2020;27(7):388–392
      OpenUrlPubMed
    34. ↵
      1. Fernandes DM,
      2. Oliveira CR,
      3. Guerguis S, et al
      ; Tri-State Pediatric COVID-19 Research Consortium Authors. SARS-CoV-2 clinical syndromes and predictors of disease severity in hospitalized children and youth [published online ahead of print November 13, 2020]. J Pediatr. doi:10.1016/j.jpeds.2020.11.016
    35. ↵
      1. Garg S,
      2. Kim L,
      3. Whitaker M, et al
      . Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458–464
      OpenUrlCrossRefPubMed
    36. ↵
      1. Kim L,
      2. Whitaker M,
      3. O’Halloran A, et al.; COVID-NET Surveillance Team
      . Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 1-July 25, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1081–1088
      OpenUrlPubMed
    37. ↵
      1. Williams N,
      2. Radia T,
      3. Harman K,
      4. Agrawal P,
      5. Cook J,
      6. Gupta A
      . COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review of critically unwell children and the association with underlying comorbidities [published online ahead of print September 10, 2020]. Eur J Pediatr. doi:10.1007/s00431-020-03801-6
      OpenUrlCrossRef
    38. ↵
      1. Belot A,
      2. Antona D,
      3. Renolleau S, et al
      . SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill. 2020;25(22):2001010
      OpenUrl
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    Factors Associated With Severe SARS-CoV-2 Infection
    Naïm Ouldali, David Dawei Yang, Fouad Madhi, Michael Levy, Jean Gaschignard, Irina Craiu, Tamazoust Guiddir, Cyril Schweitzer, Arnaud Wiedemann, Mathie Lorrot, Anne-Sophie Romain, Aurélie Garraffo, Hervé Haas, Sébastien Rouget, Loïc de Pontual, Camille Aupiais, Alain Martinot, Julie Toubiana, Laurent Dupic, Philippe Minodier, Manon Passard, Alexandre Belot, Corinne Levy, Stephane Béchet, Camille Jung, Mayssa Sarakbi, Sarah Ducrocq, Nevena Danekova, Imen Jhaouat, Olivier Vignaud, Nathalie Garrec, Elisabeth Caron, Robert Cohen, Vincent Gajdos, François Angoulvant, on behalf of the investigator group of the PANDOR study
    Pediatrics Mar 2021, 147 (3) e2020023432; DOI: 10.1542/peds.2020-023432

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    Factors Associated With Severe SARS-CoV-2 Infection
    Naïm Ouldali, David Dawei Yang, Fouad Madhi, Michael Levy, Jean Gaschignard, Irina Craiu, Tamazoust Guiddir, Cyril Schweitzer, Arnaud Wiedemann, Mathie Lorrot, Anne-Sophie Romain, Aurélie Garraffo, Hervé Haas, Sébastien Rouget, Loïc de Pontual, Camille Aupiais, Alain Martinot, Julie Toubiana, Laurent Dupic, Philippe Minodier, Manon Passard, Alexandre Belot, Corinne Levy, Stephane Béchet, Camille Jung, Mayssa Sarakbi, Sarah Ducrocq, Nevena Danekova, Imen Jhaouat, Olivier Vignaud, Nathalie Garrec, Elisabeth Caron, Robert Cohen, Vincent Gajdos, François Angoulvant, on behalf of the investigator group of the PANDOR study
    Pediatrics Mar 2021, 147 (3) e2020023432; DOI: 10.1542/peds.2020-023432
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