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Comorbidities, clinical characteristics and outcomes of COVID-19 in pediatric patients in a tertiary medical center in the Netherlands

  • Amsterdam University Medical Centers location Academic Medical Center
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World Journal of Pediatrics
Comorbidities, clinical characteristics andoutcomes ofCOVID‑19
inpediatric patients inatertiary medical center intheNetherlands
AmritaBiharie1 · Maya W.Keuning1· Katja C.Wolthers2· DasjaPajkrt1
Received: 29 December 2021 / Accepted: 27 April 2022
© Children's Hospital, Zhejiang University School of Medicine 2022
* Amrita Biharie
1 Department ofPediatric Infectious Diseases, Rheumatology
andImmunology, Amsterdam University Medical
Centers Location Academic Medical Center, University
ofAmsterdam, Meibergdreef 9, 1105AZAmsterdam,
2 Department ofMedical Microbiology, Amsterdam University
Medical Centers Location Academic Medical Center,
University ofAmsterdam, Amsterdam, Netherlands
Having pre-existing comorbidities is described as a risk
factor for more severe disease in adult corona virus disease
2019 (COVID-19) and in infections with SARS-CoV-1 and
MERS-CoV [1]. In adult SARS-CoV-2 infections, patients
with pre-existing underlying comorbidities, such as chronic
obstructive pulmonary disease, cardiovascular disease, dia-
betes and obesity, are more likely to have severe disease
compared to healthy adults [2]. An inconsistency is seen in
current findings on the association with comorbidities and
pediatric COVID-19 severity. An important limitation in cur-
rently available studies is limited data: severe disease is rare
in children compared to adults, and most studies describe
COVID-19 severity merely by reporting intensive care unit
(ICU) admission or mortality rates instead of detailed data
on clinical presentation and outcomes.
A severe manifestation of SARS-CoV-2 infection is multi
inflammatory syndrome in children (MIS-C), which usually
follows weeks after SARS-CoV-2 infection and is charac-
terized by gastrointestinal symptoms, muco-cutaneous signs
and cardiovascular involvement. Several studies describe the
association between comorbidities and incidence or mortal-
ity of MIS-C [3, 4]. To our knowledge, there are no data on
the association between pre-existing comorbidities and the
severity of MIS-C.
Thus, the primary aim of this retrospective study was
to describe in detail the pre-existing comorbidities and the
severity of SARS-CoV-2 infections in pediatric patients in a
tertiary medical center in the Netherlands. Second, we aimed
to assess the association between comorbidities and disease
severity of both acute COVID-19 and MIS-C in pediatric
patients. These data will help to determine which groups
of children are more vulnerable to severe acute COVID-19
and severe MIS-C, which could aid development of clinical
SARS-CoV-2 infection care and management strategies.
This retrospective, observational cohort study was car-
ried out at the tertiary medical center, Amsterdam UMC,
the Netherlands. Inclusion criteria were in- and outpatients
younger than or equal to 18years with a positive polymer-
ase chain reaction (PCR) test or serum antibodies (total Ig)
against SARS-CoV-2 between March 2020 and April 2021.
Patients were excluded when no data on clinical characteris-
tics of the SARS-CoV-2 infection were available.
Data describing pre-existing comorbidities, COVID-19
severity and clinical outcomes were retrieved from medi-
cal records. Comorbidities were assessed by extracting data
on pre-existing disorders based on ICD-10 codes and body
mass index (BMI). A pre-existing disorder was found to be
relevant when the disorder could potentially interact with
the immune system or other bodily functions which could
influence disease severity. The pre-existing comorbidities
were classified into comorbidity groups based on the affected
organ system. We used the definition of childhood obesity
using BMI corrected for age and sex in 2000 by Cole etal.,
to assess the prevalence of obesity for patients aged 2 years
or older [5].
Disease severity of pediatric acute COVID-19 was classi-
fied by Dong etal. into five categories: asymptomatic, mild,
moderate, severe and critical [6]. For statistical analyses,
asymptomatic, mild and moderate cases were combined
as non-severe disease, and severe and critical cases were
combined as severe disease. Based on the WHO criteria for
MIS-C and parallel to the classification mentioned above,
the severity of MIS-C was described as moderate, severe or
critical [6, 7]. Moderate cases were classified as non-severe,
and severe and critical disease were combined as severe dis-
ease for the statistical analysis. Clinical outcome described
hospitalization, ICU admission and mortality rates in both
World Journal of Pediatrics
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acute COVID-19 and MIS-C. Long-term symptoms after
acute COVID-19, known as post-COVID-19 syndrome, were
reported based on the clinical definition of post-COVID-19
syndrome according to the NICE guidelines [8]; symptoms
that developed during or after acute COVID-19 continuing
for more than 12weeks.
Data analysis was performed with Statistical Package for
the Social Sciences (SPSS) using Fisher’s or Fisher–Free-
man–Halton exact tests. A P value < 0.05 was considered
statistically significant. Odds ratios were calculated to
describe strengths of associations. In case of contingency
tables containing a value of zero, Firth’s penalized logistic
regression was used to calculate a corresponding odds ratio
for the Fisher’s exact test to mitigate sparse data bias [9].
A total of 83 patients were included in this study, among
which 46 patients had pre-existing comorbidities. In Table1,
data on demographics and patient characteristics are summa-
rized. Most common pre-existing comorbidities were obe-
sity (n = 10, 21.7%), respiratory disorders (n = 9, 19.6%) and
neurological disorders (n = 8, 17.4%). For a detailed descrip-
tion of pre-existing comorbidities in each comorbidity group
(Supplementary table).
From the 58 patients with acute COVID-19, 38 (65.5%)
had a pre-existing comorbidity. Most patients had mild
COVID-19 disease, in the patient group without comor-
bidities (n = 16, 80.0%) as well as in the patient group with
comorbidities (n = 24, 63.2%). All the eight patients with
severe or critical disease (13.8%), had pre-existing comor-
bidities. One of these patients died due to the consequences
of COVID-19. Table2 summarizes data on severity and hos-
pital admission per group (comorbidities versus no comor-
bidities). More severe acute COVID-19 was seen in patients
Table 1 Patient characteristics and key demographics
a Patients with negative or unknown PCR results were included only when (IgM and/or IgG) antibodies against SARS-CoV-2 in serum were pre-
sent. IQR interquartile range.
Patient characteristics No comorbidities
(n = 37)
(n = 46)
Sex, n (%)
Male 23(62.2) 23 (50.0)
Female 14 (37.8) 23 (50.0)
Age, year, median (IQR) 11.0 (4.5–14.5) 11.5 (4.8–16.0)
Weight, kg, median (IQR) 44.3 (26.6–57.3) 45.7 (19.5–64.0)
Height, cm, median (IQR) 154.0 (122.5–168.0) 145.0 (110.0–168.0)
BMI, median (IQR) 18.6 (16.6–20.7) 18.9 (16.0–23.8)
Pre-existing comorbidities, n (%)
Obesity 10 (21.7)
Respiratory disorder 9 (19.6)
Systemic auto immune disorder 3 (6.5)
Neurological disorder 8 (17.4)
Cardiovascular disorder 5 (10.9)
Endocrine system disorder 4 (8.7)
Hematological disorder 2 (4.3)
Gastrointestinal disorder 3 (6.5)
Urogenital system disorder 6 (13.0)
Genetic/chromosomal abnormalities 6 (13.0)
Cancer 2 (4.3)
Other comorbidities 4 (8.7)
Pharmacological treatment, n (%) 27 (58.7)
Immunosuppressant medication 7 (15.2)
PCR confirmed SARS-CoV-2 infection, n (%) 22 (59.5) 37 (80.4)
PCR result negative or unknown, n (%)a15 (40.5) 9 (19.6)
Reason for testing, n (%)
Unknown 5 (13.5) 4 (8.7)
Clinical suspicion of SARS-CoV-2 infection 31 (83.8) 39 (84.8)
Symptoms suspicious for COVID-19 31 (83.8) 33 (71.7)
Contact with COVID-19 case 10 (27.0) 15 (32.6)
Routinely (before procedure) 1 (2.7) 2 (4.3)
World Journal of Pediatrics
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with pre-existing comorbidities compared to those without
comorbidities (P = 0.041, OR 11.42, 95% CI 1.29–1507.49).
Patients with a pre-existing comorbidity also had a higher
risk of being admitted to the ICU (P = 0.032, OR = 11.72,
95% CI 1.31–1547.79) than those without comorbidities.
In particular, the presence of a neurological disorder
was found to be associated with acute COVID-19 severity
(P = 0.004, OR 16.11, 95% CI 2.51–103.55). In the group
of neurological disorders, 63% had epilepsy or frequent sei-
zures, 50% had cerebral palsy, and other disorders included
hydrocephalus and myasthenia gravis. Other main groups of
disorders, such as obesity or respiratory disorders, did not
show a significant association with disease severity. Table3
contains the difference in acute COVID-19 severity (non-
severe vs severe) between all comorbidity groups.
Twenty-eight patients were diagnosed with MIS-C as a
manifestation of SARS-CoV-2 infection. Twenty-five per-
cent of MIS-C patients (n = 7) had a pre-existing comor-
bidity. Twelve patients (42.9%) met the criteria for critical
disease (Table2). The majority of MIS-C patients did not
have comorbidities, and no significant associations between
comorbidities and severity of MIS-C were found. The key
findings of this study indicate that, although most pediatric
patients have non-severe disease, children with pre-existing
comorbidities are more likely to have more severe acute
COVID-19 than children without comorbidities. In particu-
lar, pediatric neurological disorders were associated with
more severe COVID-19.
Considerable inconsistency is seen in current evidence on
the association between comorbidities and pediatric COVID-
19 severity. A meta-analysis by Tsankov etal. combined
the findings of several heterogeneous articles, concluding
an association between comorbidities and acute COVID-
19 severity [10]. However, most of the included studies
had a small sample size and only described the association
between comorbidities and ICU admission or mortality rate
instead of severity as a detailed description of clinical char-
acteristics. This could create selection bias because children
with comorbidities could be admitted to the ICU as a preven-
tative measure instead of due to clinical deterioration [10].
Our study methods included a detailed clinical evaluation to
describe COVID-19 disease severity following a classifica-
tion system in addition to ICU admission.
Corroborating our findings, two studies, performed in
other countries and using a similar classification system,
found that children with comorbidities have a higher risk
for more severe COVID-19, including a larger cohort of
3837 pediatric patients [11, 12]. The other study also found
an association between more severe COVID-19 and neuro-
logical disorders, which included mostly epilepsy or severe
neuro-disability similar to the patients in our study [11].
Another multicenter observational study in the UK also
found that among comorbidities in patients who needed criti-
cal care due to COVID-19, neurological disorders (such as
neurodisability) were one of the most common [13]. Neuro-
logical disabilities, such as cerebral palsy, which influence
motor functions, could lead to difficulties in spontaneous
breathing and clearing respiratory secretions, which could
worsen respiratory infections and thus explain this associa-
tion with more severe acute COVID-19. Moreover, SARS-
CoV-2 can affect the nervous system through damage to
neuronal cells, muscle tissues and vascular cells, which are
likely to be more vulnerable in children with comorbidities
In contrast, three of the studies that used a similar
classification of severity, all with relatively small sample
sizes, found that having comorbidities was not associated
with disease severity in pediatric patients [1517]. This
inconsistency is possibly due to the missing consensus
on definitions of relevant pre-existing comorbidities and
to a missing universal classification of disease severity
of acute COVID-19. In our results, we particularly did
not find an association between obesity and severity of
acute COVID-19, which has been seen in some other stud-
ies [10, 11]. It is thought that higher visceral adiposity is
associated with higher inflammatory cytokine levels cor-
related with COVID-19 severity, which might explain why
more severe acute COVID-19 can be seen in obese patients
[10]. We also do not report an association between res-
piratory disorders, such as asthma, and acute COVID-19
severity, which is in accordance with findings related to
SARS-CoV-1 and MERS-CoV infections [18]. It is sug-
gested that human coronaviruses may not have the capac-
ity to enhance asthmatic inflammation, unlike the human
rhinovirus or respiratory syncytial virus [18].
Our findings imply that having comorbidities is not a
risk factor for having more severe MIS-C compared to
having no comorbidities. This is in accordance with previ-
ous findings that pre-existing comorbidities among MIS-C
patients are rare [3]. Healthcare professionals should be
aware of the association between pre-existing comorbidi-
ties and severity of COVID-19 to determine adequate man-
agement strategies for this specific group. Furthermore,
the implications made in this study should be taken into
consideration in the debate on SARS-CoV-2 vaccination
in children. It is worth noting that the absolute numbers
of severe disease due to acute pediatric COVID-19 are
low and that the size of the effect comorbidities has on
disease severity remains uncertain. However, effects of
the COVID-19 pandemic on children in particular, such as
social isolation and interruption in education, also should
be considered in future management or prevention strate-
gies [19]. This study substantiates the need for large-scale
studies with well-defined evaluation and classification
World Journal of Pediatrics
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of disease severity to determine the true strength of the
The strengths of this study include the detailed informa-
tion on clinical characteristics and outcomes to carefully
assess the severity of COVID-19 infection and the asso-
ciation between the severity of MIS-C and pre-existing
Our study has a few limitations. First, the retrospec-
tive observational study design may cause residual con-
founding. Second, because severe COVID-19 and hospital
admission is rare in children, our study consisted of a small
sample size. Selection bias may have affected the results,
because asymptomatic or mild children are not always
PCR-confirmed and, therefore, are under-represented.
Owing to the small sample, there was sparsity in numbers
included for statistical analyses, which contributes to the
broad confidence intervals. Various international databases
have been set up to prospectively study COVID-19 sever-
ity in patients with comorbidities, a promising develop-
ment [10]. Third, the study was carried out at a tertiary
center where mostly severely ill children or children with
complex comorbidities are treated, which can cause selec-
tion bias.
In conclusion, our findings show that pediatric acute
COVID-19 is mostly non-severe, but children with pre-
existing comorbidities are at risk for developing more severe
acute COVID-19 compared to patients without comorbidi-
ties. MIS-C is generally more severe than acute COVID-19.
However, no association was found between comorbidities
and severity of MIS-C. More prospective large-scale data
on the susceptibility of children with comorbidities for
severe acute COVID-19 are needed, as well as more data on
Table 2 Severity of disease and outcomes
Outcomes No comorbidities Comorbidities
Acute COVID-19 (n = 58) n = 20 n = 38
Severity, n (%)
Asymptomatic 0 (0) 2 (5.3)
Mild 16 (80.0) 24 (63.2)
Moderate 4 (20.0) 25 (10.5)
Severe 0 (0) 4 (13.2)
Critical 0 (0) 3 (7.9)
Hospital admission, n (%) 7 (35.0) 12 (31.6)
ICU admission, n (%) 0 (0) 6 (15.8)
Hospitalization duration, d, median (IQR)
Hospital admission 3.0 (0.0–6.0) 4.0 (2.0–11.0)
ICU admission 0 (0) 2.5 (1.8–10.3)
Mortality, n (%) 0 (0) 1 (2.6)
Post COVID syndrome, n (%) 6 (30.0) 2 (5.3)
Fatigue 4 (20.0) 2 (5.3)
Dyspnea 2 (10.0)
Concentration problems 2 (10.0)
Dizzines 1
MIS-C, n = 28 n = 21 n = 7
Severity, n (%)
Moderate 7 (33.3) 1 (14.3)
Severe 6 (28.6) 2 (28.6)
Critical 8 (38.1) 4 (57.1)
Hospital admission, n (%) 21 (100.0) 7 (100.0)
ICU admission, n (%) 11 (52.4) 5 (71.4)
Hospitalization duration, d, median (IQR)
Hospital admission 7.0 (5.0–8.0) 7 (7.0–10.0)
ICU admission 5.0 (3.0–6.0) 3.0 (2.5–6.5)
Mortality, n (%) 0 (0) 1 (0)
Long term complaints, n (%) 3 (14.3) 1 (14.3)
World Journal of Pediatrics
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risk factors for developing severe MIS-C to establish man-
agement strategies for SARS-CoV-2 infections in specific
groups of pediatric patients.
Supplementary Information The online version contains supplemen-
tary material available at https:// doi. org/ 10. 1007/ s12519- 022- 00564-y.
Author contributions AB: conceptualization, data curation, formal
analysis, investigation, methodology, project administration, visualiza-
tion, writing—original draft, and writing—review and editing; MWK:
conceptualization, project administration, visualization, writing—origi-
nal draft, and writing—review and editing; KCW: data curation and
resources; DP: conceptualization, project administration, resources,
software, supervision, and validation.
Funding None.
Data availability The data sets generated during and/or analyzed dur-
ing the current study are available from the corresponding author on
reasonable request.
Ethical approval Approval and a waiver for the Medical Research
Involving Human Subjects Act was provided by the local medical
ethics review committee of Amsterdam UMC (Reference number
Conflict of interest No financial or non-financial benefits have been re-
ceived or will be received from any party related directly or indirectly
to the subject of this article.
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P value
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... In adult SARS-CoV-2 infections, patients with pre-existing underlying comorbidities, such as chronic obstructive pulmonary disease, cardiovascular disease, diabetes, and obesity, are more likely to have severe disease compared to healthy adults [15]. An inconsistency is seen in current findings on the association with comorbidities and pediatric COVID-19 severity [16]. Patients with comorbidities may have conflicting COVID-19 vaccine attitudes. ...
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Background To date, information on COVID-19 pediatric patients is still sparse. We aimed to highlight the epidemiological and clinical data regarding SARS-CoV-2 infection in children and adolescents to improve the understanding of the disease in this age group and inform physicians during the ongoing COVID-19 pandemic. Methods We conducted a retrospective, observational study in “Marie Curie” Emergency Children’s Hospital from Bucharest, Romania. We analyzed clinical and epidemiological characteristics of the patients confirmed with SARS-CoV-2 infection, between April 1, 2020–October 31, 2020. Results A total of 172 patients aged 0–18 years were included, 79 (45.93%) female and 93 (54.07%) male patients. 28 (16.28%) patients had co-morbidities (more often identified in asymptomatic group; p < 0.0001). 47 (27.32%) had exposure to an identified source. 30 (17.44%) patients were asymptomatic; 142 (85.56%) had mild or moderate disease. The most frequent symptoms were: pyrexia (78.87%), digestive symptoms (50%), cough (40.14%). Chest X-ray was performed in 50 patients and it was abnormal in half of them, all being symptomatic. About 2/3 of the evaluated patients had normal leukocytes. The most common hematological change was lymphopenia; monocytes tended to be higher in symptomatic patients. About 40% of the patients were admitted; none required admission to ICU. No significant differences were found between symptomatic and asymptomatic patients regarding gender, age distribution, and exposure to a source. Conclusions All the patients had asymptomatic, mild or moderate disease. Patients with comorbidities, classically considered high risk patients, presented the same pattern of disease.
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An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases. Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial.What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.
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Objective There is limited information on the severity of COVID-19 infection in children with comorbidities. We investigated the effects of pediatric comorbidities on COVID-19 severity by means of a systematic review and meta-analysis of published literature. Methods PubMed, Embase, and Medline databases were searched for publications on pediatric COVID-19 infections published January 1st to October 5th, 2020. Articles describing at least one child with and without comorbidities, COVID-19 infection, and reported outcomes, were included. Results 42 studies containing 275,661 children without comorbidities and 9,353 children with comorbidities were included. Severe COVID-19 was present in 5.1% of children with comorbidities, and in 0.2% without comorbidities. Random-effects analysis revealed a higher risk of severe COVID-19 among children with comorbidities than for healthy children; relative risk ratio 1.79 (95% CI 1.27 – 2.51;I² = 94%). Children with underlying conditions also had a higher risk of COVID-19-associated mortality; relative risk ratio 2.81 (95% CI 1.31 – 6.02; I² = 82%). Children with obesity had a relative risk ratio of 2.87 (95% CI 1.16 – 7.07 I² = 36%). Conclusions Children with comorbidities have a higher risk of severe COVID-19 and associated mortality than children without underlying disease. Additional studies are required to further evaluate this relationship.
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Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 10 ⁹ /L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group. Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). Study registration ISRCTN66726260.
Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.
MIS-C occurs among persons aged <21 years following SARS-CoV-2 infection. Among 2,818 MIS-C cases, 35 (1.2%) deaths were reported, primarily affecting racial/ethnic minority persons. Being 16–20 years old or having comorbidities was associated with death. Targeting COVID-19 prevention among these groups and their caregivers might prevent MIS-C–related deaths.
Purpose of review: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes coronavirus disease 2019 (COVID-19), has caused substantial morbidity and mortality. Operation Warp Speed aims to accelerate the development of a safe and effective vaccine by early 2021. Multiple vaccine candidates with reassuring safety and efficacy profiles have advanced to phase 3 clinical trials in adults. The purpose of this review is to describe the burden of COVID-19 in children, to update pediatricians about adult COVID-19 vaccine clinical trials, to discuss the importance of COVID-19 vaccine trials in children and to instill confidence in the established vaccine development and licensure processes. Recent findings: Children of all ages are at risk for SARS-CoV-2 infection and severe disease manifestations. Children are also susceptible to downstream effects of COVID-19, including social isolation and interruption in education. Developing a pediatric COVID-19 vaccine could prevent disease, mitigate downstream effects and enable children to re-engage in their world. Summary: Children could benefit both directly and indirectly from vaccination. In light of the safety and immunogenicity results from recent adult COVID-19 vaccine clinical trials, children should have the opportunity to be included in clinical trials in parallel to ongoing adult phase 3 clinical trials in a manner that is careful, methodical and transparent.
There are growing evidence of clinical manifestations other than acute respiratory syndrome in severe acute respiratory syndrome associated with coronavirus 2-infected children. In our multicenter retrospective analysis, we observed among 127 severe acute respiratory syndrome associated with coronavirus 2 positive children that the presence of gastrointestinal symptoms was more frequently associated with severe and critical phenotype (P = 0.029). Moreover, having gastrointestinal symptoms was more frequently reported in patients who developed cardiac impairment.
Human coronaviruses (HCoVs) such as HCoV‐229E or OC43 are responsible for mild upper airway infections, whereas highly pathogenic HCoVs, including SARS‐CoV, MERS‐CoV and SARS‐CoV‐2, often evoke acute, heavy pneumonias. They tend to induce immune responses based on interferon and host inflammatory cytokine production and promotion of T1 immune profile. Less is known about their effect on T2‐type immunity. Unlike human rhinoviruses (HRV) and rhinosyncytioviruses (RSV), HCoVs are not considered as a dominant risk factor of severe exacerbations of asthma, mostly T2‐type chronic inflammatory disease. The relationship between coronaviruses and T2‐type immunity, especially in asthma and allergy, is not well understood. This review aims to summarise currently available knowledge about the relationship of HCoVs, including novel SARS‐CoV‐2, with asthma and allergic inflammation.