R.S. serves as an Associate Editor for The Journal of Pediatrics. The other authors
declare no conflicts of interest.
Despite worldwide spread of SARS-CoV-2, few publications have reported the potential
for severe disease in the pediatric population. We report 177 infected children and
young adults, including 44 hospitalized and 9 critically ill patients, with comparison
of patient characteristics between infected hospitalized and non-hospitalized cohorts,
as well as critically ill and non-critically ill cohorts. Children <1 year and adolescents
/young adults >15 years of age were over-represented among hospitalized patients (P
= .07). Adolescents/young adults were over-represented among the critically ill cohort.
(P = .02).
Since the emergence and worldwide spread of Severe Acute Respiratory Syndrome Coronavirus-
2 (SARS-CoV-2), published summaries have predominantly highlighted that children represent
a small proportion (<2%) of COVID-19 cases, including hospitalizations and deaths.1,
2, 3 Although children and young adults clearly are susceptible to SARS-CoV-2 infection,
attention has focused primarily on their potential role in influencing spread and
community transmission rather than the potential severity of infection in children
and young adults themselves. Reanalyzed data from the epicenter of the Chinese outbreak
noted that children represented 12% of infections.
4
To date, reports of severe disease in international pediatric populations have been
limited, primarily descriptive, and in the United States, limited only to incomplete
public health epidemiologic data.5, 6, 7, 8, 9
Methods
This observational retrospective cohort study included 177 children and young adults
with clinical symptoms and laboratory confirmed (177/1804; 9.8% of tested) SARS-CoV-2
infection treated between March 15 and April 30, 2020 at the Children’s National Hospital,
a large freestanding medical center located in Washington DC. These 177 patients came
to medical attention for clinical evaluation of symptoms to our emergency departments,
ambulatory clinics, inpatient units, or by referral for admission from external facilities.
From these 177 infected patients, we identified cohorts of non-hospitalized (N=133)
and hospitalized (N=44) patients. Of the 44 hospitalized patients, we identified cohorts
of non-critically ill (N=35) and critically ill (N=9) patients. The objective of the
study was to determine if specific epidemiologic and clinical patient characteristics
were more likely to be associated with hospitalization and/or critical care. Data
were extracted from medical records and recorded in a RedCap database, including age,
sex, presence or absence of underlying medical condition and presence or absence of
fever or respiratory symptoms (rhinorrhea, sore throat, cough, shortness of breath),
as well as other symptoms (diarrhea/vomiting, myalgia, chest pain, loss of sense of
taste or smell, headache). The Fisher exact test was performed to examine differences
in the distribution of categorical variables between hospitalized vs. non-hospitalized
patients, as well as between hospitalized critically ill patients vs. non-critically
ill patients. Continuous variables were evaluated using logistic regression. This
project was submitted to the IRB and was determined to be a Quality Improvement initiative
and not human subjects research.
Results:
Of the 177 pediatric and young adult SARS-CoV-2 infected patients, 44/177 patients
(25%) required hospitalization, of which 35/44 (80%) were non-critically ill and 9/44
(20%) were critically ill.
Age: Children and young adults from all age groups were infected by SARS CoV-2, with
a median age of 9.6 years (range 0.1-34.2 years of age). The median age of SARS-CoV-2
infected hospitalized patients compared with non-hospitalized patients was not significantly
different (9.6 years versus 9.5 years), but the median age of critically ill patients
compared with non-critically ill patients was significantly higher (17.3 years versus
3.6 years; P =.04) (
Table I
). We found no overall difference in the representation of different age groups within
the hospitalized and non-hospitalized cohorts, nor between the critically ill and
non-critically ill cohorts. However, we noted a bimodal distribution of patients less
than one year of age and patients >15 years of age representing the largest proportion
of patients within the SARS CoV-2 infected hospitalized and critically ill cohorts.
Children <1 year of age and children/young adults >15 years of age each represented
32% (14/44) of all hospitalized patients, accounting for a total of 64% of hospitalizations
(p=0.07). Adolescents and young adults > 15 years of age represented 66% (6/9) of
critical care admissions (p=0.02). (Figure
).
Table 1
Epidemiologic Characteristics and Clinical Features of 177 Children and Young Adults
with Symptomatic SARS-CoV-2 Infection
Characteristic
Total, Non-hospitalized and Hospitalized (N=177)
Non-Hospitalized (N=133)
Hospitalized (N=44)
p value
Hospitalized, Non-Critical Care (N=35)
Hospitalized, Critical Care (N=9)
p value
Age (years)
Median (range)
9.6 (0.1-34.2)
9.5 (0.1-34.2)
9.6 (0.1-25.6)
0.75
3.6 (0.1-21.5)
17.3 (0.1-25.6)
0.04
Distribution — no. (%)
<1 yr
43 (24%)
29 (22%)
14 (32%)
0.22
13 (37%)
1 (11%)
0.15
1–4 yr
26 (15%)
19 (14%)
7 (16%)
6 (17%)
1 (11%)
5–9 yr
23 (13%)
21 (16%)
2 (5%)
2 (6%)
0 (0%)
10-14 yr
36 (21%)
29 (22%)
7 (16%)
6 (17%)
1 (11%)
15-20 yr
37 (21%)
28 (21%)
9 (20%)
6 (17%)
3 (33%)
>20 yr
12 (7%)
7 (5%)
5 (11%)
2 (6%)
3 (33%)
Sex – no (%)
Male
92 (52%)
70 (53%)
22 (50%)
0.76
16 (46%)
6 (67%)
0.26
Female
85 (48%)
63 (47%)
22 (50%)
19 (54%)
3 (33%)
Underlying Medical Condition
Yes
69 (39%)
42 (32%)
27 (63%)
0.001
20 (57%)
7 (78%)
0.45
No
96 (55%)
80 (60%)
16 (37%)
14 (40%)
2 (22%)
Unknown
11 (6%)
11 (8%)
0
-
0
0
-
Reported underlying medical condition
Asthma
35 (20%)
28 (21%)
7 (16%)
0.46
5 (14%)
2 (22%)
0.62
Diabetes
5 (3%)
3 (2%)
2 (5%)
0.43
1 (3%)
1 (11%)
0.37
Neurologic
11 (6%)
3 (2%)
8 (19%)
<0.001
5 (14%)
3 (33%)
0.33
Obesity
4 (2%)
3 (2%)
1 (2%)
1.00
0 (0%)
1 (11%)
0.21
Cardiac
5 (3%)
1 (1%)
4 (9%)
0.004
2 (6%)
2 (22%)
0.18
Hematologic
6 (3%)
2 (2%)
4 (9%)
0.004
4 (11%)
0 (0%)
0.57
Oncologic
2 (1%)
0 (0%)
2 (5%)
0.013
2 (6%)
0 (0%)
1.00
Symptoms Present at the time of visit
nbsp
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nbsp
nbsp
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Fever
116 (66%)
82 (62%)
34 (77%)
0.06
27 (77%)
7 (78%)
0.97
Sore throat or congestion
77 (44%)
66 (50%)
11 (25%)
0.004
10 (29%)
1 (11%)
0.28
Cough
99 (56%)
83 (62%)
16 (37%)
0.003
12 (34%)
4 (44%)
0.57
Shortness of breath
27 (15%)
16 (12%)
11 (26%)
0.04
7 (20%)
4 (44%)
0.13
Diarrhea or vomiting
27 (15%)
20 (15%)
7 (15%)
0.89
5 (14%)
2 (22%)
0.56
Myalgia
25 (14%)
21 (16%)
4 (9%)
0.27
2 (6%)
2 (22%)
0.59
Chest Pain
16 (9%)
10 (8%)
6 (14%)
0.22
4 (11%)
2 (22%)
0.40
Loss of Sense of Taste and/or Smell
15 (9%)
13 (10%)
2 (5%)
0.28
2 (6%)
0 (0%)
1.00
Headache
25 (14%)
24 (18%)
1 (2%)
0.01
1 (3%)
0 (0%)
1.00
Figure 1
Age Distribution of SARS-CoV-2- Infected, Hospitalized, and Critically Ill Cases
Sex: Males and females were equally represented within the total SARS CoV-2 infected
cohort (52% male, 48% female), as well as the infected hospitalized cohort (50% male,
50% female). There was a predominance of males in the critically ill hospitalized
cohort (67% male, 33% female); but this was not statistically significant (p=0.26)
Underlying Medical Conditions: Underlying medical conditions were also present in
69/177 (39%) of all patients with SARS-CoV-2 infection. The most frequent underlying
diagnosis overall was asthma (35/177; 20%), but also included neurologic (6%), diabetes
(3%), obesity (2%), cardiac (3%), hematologic (3%) and oncologic (1%) underlying conditions
Underlying conditions were more common as a whole in the SARS-CoV2 infected hospitalized
cohort (27/44; 63%) compared with the infected non-hospitalized cohort (42/133; 32%;
p=0.001). Several specific underlying conditions were more common in the hospitalized
as non-hospitalized patients. Specifically, neurological disorders were more common
in the hospitalized cohort (8/44; 19%; p<0.001) compared with the non-hospitalized
cohort (3/133; 2%; p<0.001). Additionally, cardiac (p=0.004), hematologic (p=0.004),
and oncologic (p=0.013) diagnoses were more common in the hospitalized as compared
with the non-hospitalized cohort. Although asthma was the most prevalent underlying
condition overall, it was not more common in the hospitalized cohort (7/44; 16%) compared
with the non-hospitalized cohort (28/133; 21%; p =0.46), nor more common in the critically
ill cohort (2/11; 22%) compared with the non-critically ill cohort (5/35; 14%; p=0.62).
Comparing the SARS-CoV-2 infected non-critically ill and critically ill hospitalized
patients, there were no significant difference in the presence of underlying conditions
overall or any specific underlying diagnosis. Of note, there was no underlying condition
present in 96/177 (55%) SARS-CoV-2 infected patients overall, 16/44 (37%) hospitalized
patients and 2/9 (22%) critically ill patients.
Symptoms: The majority (134/177; 76%) of SARS-CoV-2 infected patients came to medical
attention with respiratory symptoms (rhinorrhea, congestion, sore throat, cough or
shortness of breath) with or without fever. However, only 85/177 (48%) had both fever
and respiratory symptoms present. Fever was present in 116/177 (66%) of SARS-CoV-2
infected patients but was not more common in the infected hospitalized cohort (34/44,
77%) compared with the infected non-hospitalized cohort (82/133, 62%; p=0.46). Shortness
of breath was more common in the hospitalized cohort (11/44, 26%) compared with non-hospitalized
(16/133, 12%; p=0.04). However, less severe respiratory symptoms including sore throat/congestion
(p=0.004), or cough (p=0.003) as well as headache (p=0.01) were more common in the
non-hospitalized cohort. Other symptoms were also present, including diarrhea/vomiting
(27/177, 15%), myalgia (25/177, 14%), chest pain (16/177, 9%) and loss of sense of
smell or taste (15/177, 9%), but presence of these symptoms did not vary significantly
between cohorts. Patients in the critically ill cohort were not more likely to have
fever or any other specific symptom compared with the non-critically ill cohort.
Critically Ill Cohort: Eight (8) of 9 (89%) SARS-CoV-2 infected critically-ill patients
required some level of respiratory support, with 4 requiring mechanical ventilation
(3 meeting the definition of Acute Respiratory Distress Syndrome, 2 meeting the definition
of multiple organ failure), 3 requiring Bi-level positive airway pressure (BiPAP),
1 requiring nasal non-invasive ventilation via a RAM cannula and 1 via high-flow nasal
cannula. One patient had features consistent with the recently emerged Kawasaki disease-like
presentation with hyper-inflammatory state, hypotension and profound myocardial depression.
Details regarding these critically-ill patients including the maximum respiratory
support required are summarized in the Table 2
(available at www.jpeds.com
).
Table 2
(Online): Details of Critically Ill SARS-CoV-2 Infected Children and Young Adults
Age
Sex
Underlying Diagnosis
Clinical Features
Ventilatory Support
7 weeks
Female
Trisomy 21Atrial Septal Defect
Symptom onset 12 days prior to admission: Tachypnea, vomiting, diarrhea. Admitted
on days 3-5 of symptoms for NC 02; SARS CoV-2 PCR negative. Readmission 3 days later
due to progressive tachypnea, fever. CXR with right lower lobe pneumonia. Repeat SARS
Cov-2 PCR positive.
RAM cannula
4 years
Male
None
Symptom onset 5 days prior to admission: consistent with Kawasaki Disease (fever,
rash, strawberry tongue, cervical lymphadenopathy) presenting in hypotensive shock.
Markedly decreased myocardial function consistent with myocardial injury. Initial
2 COVID tests negative, 3rd positive (lower respiratory specimen). Presentation consistent
with severe hyper-inflammatory state (affecting myocardium) . Treated with IVIG, aspirin
and anakinra.
Intubated-PRVC supportHighest FiO2:1.00 at intubation, but stabilized to 0.40 FiO2PEEP-8
10 years
Male
Static EncephalopathyGlobal Developmental DelayChronic Lung DiseaseSeizure disorderAsthma
Acute onset fever, increased work of breathing and decreased oxygen saturation from
baseline 1-2 liter oxygen overnight requirement (no baseline daytime oxygen requirement).
BiPAPHighest FiO2-0.50
16 years
Male
Microcephaly, Global Developmental Delay, Seizures, Gastrostomy
Symptom onset 3 days prior to admission: Fevers. Admitted after seizures, presented
in septic shock. CXR with lobar pneumonia. Elevated troponin, acute kidney injury,
liver injury, hypotensive (required pressors), hemodialysis. Treated with hydroxychloroquine.
Intubated-PRVCHighest FiO2: 0.60Highest PEEP: 10
17 years
Female
None
Symptom onset several days prior to admission: cough, congestion, myalgia. Presented
with fever and dyspnea, shortness of breath. +COVID exposure
BiPAPHighest FiO2: 0.35
19 years
Female
Type 1 Diabetes, Brian injury from prior DKA,Mild cognitive impairment
Symptom onset 5 days prior to admission: Fever, CXR with LLL consolidation. COVID
+ exposure in group home setting.
Nasal CannulaHighest O2: 100% 4L/min flow
20 years
Male
Static Encephalopathy, Traumatic Brain Injury
Symptom onset 2-3 days prior to admission: Cough, dyspnea, fever. + COVID exposure
(father)
BiPAPHighest FiO2: 0.35
23 years
Male
None
Symptom onset 5 days prior to CNH admission: Cough, fever, progressing to shortness
of breath, pleuritic chest pain, fatigue, chills, sputum production. Admitted to outside
hospital 2 days prior to transfer and received hydroxychloroquine and azithromycin,
tocilzumab, but progressed to intubation and transferred to Children’s National on
day 5 of illness. Multifocal pneumonia, MRSA bacteremia, multiorgan dysfunction, venous
thrombosis, pulmonary embolism. Received second dose tocilzumab, antibiotics.
Intubated—PRVCHighest FiO2: -1.00 (not weaned below 50%O2 since admission)Highest
PEEP: 20 (while on 100% O2)Nitrous oxide X 6 days
25 years
Male
Morbid ObesityAsthmaHypertensionTobacco Use
Symptom onset 11 days prior to admission: Mylagias, cough. Progressive respiratory
distress, hypotension leading to admission, intubation, pressor support 5 days prior
to transfer to CNH. Hypotension, diarrhea, hypokalemia, elevated troponin. Treated
with antibiotics, hydroxycholoroquine, azithromycin, tocilzumab. Transferred to CNH
on day 11 of illness. Treated with convalescent immune plasma.
Intubated-PRVCHighest FiO2: 0.60Highest PEEP: 12
Co-infection: Sixty-three (63) of the first 105 (60%) SARS-CoV-2 infected patients
underwent concomitant multiplex molecular testing for respiratory pathogens; of these,
59/63 (94%) had no evidence of co-infection. 4/63 (6%) had co-detection of routine
coronavirus, respiratory syncytial virus, or rhinovirus/enterovirus, of unclear clinical
significance.
Discussion:
The Washington, DC metropolitan region (Maryland, Virginia, and the District of Colombia)
is in the midst of a steady increase of SARS-CoV-2 circulation in the 6 weeks since
March 15, 2020 In contrast to published and anecdotal reports from other countries
and regions of the United States, our freestanding Children’s Hospital has already
evaluated and cared for a large number of children infected with SARS-CoV-2, including
a significant number of children and young adults requiring hospitalization and critical
care. This has occurred even prior to reaching the predicted peak surge of cases in
our region at the time of this interim report. Twenty-five (25) percent of patients
presenting to our hospital with symptoms required hospitalization and 5% required
critical care, including need for intubation and mechanical ventilation, BiPAP and
high-flow nasal cannula. No deaths have been reported to date, but critically ill
patients remain hospitalized on mechanical ventilation at the time of this interim
report.
Although all age groups were infected with SARs-CoV-2, the youngest (<1 year) and
oldest children/young adults (15-25 years of age) were more likely to be hospitalized,
and the oldest were the most likely to require critical care. Underlying conditions
were also present in 39% of patients with SARS-CoV-2 infection overall but hospitalized
and critically ill patients were more likely to have underlying conditions. Conversely,
approximately 55% overall, 37% of hospitalized and 22% of critically ill patients
had no underlying conditions, reinforcing the concept that social distancing and hygienic
measures to avoid infection should be taken seriously in the pediatric age group,
as well as adults.
Although asthma was the most common underlying diagnosis present in the overall group
of children and young adults with SARS-CoV-2 infection, children and young adults
with asthma were not over-represented in the hospitalized cohort or in the critically
ill cohort. This suggests that although children and young adults with asthma may
commonly experience exacerbation in response to SARS-CoV-2 infection, asthma exacerbation
is not the primary determinant of more severe disease requiring hospitalization. Many
underlying diagnoses that have been associated with more severe disease in adults
were also present in our pediatric and young adult patients. However, only neurologic,
cardiac, hematologic, and oncologic underlying diagnoses were significantly more common
in the hospitalized cohort compared with the non-hospitalized cohort, and none was
more common in the critically ill compared with the non-critically-ill cohort.
With regard to symptoms, shortness of breath was more common in hospitalized compared
with non-hospitalized children/young adults, but other features did not clearly distinguish
them from less ill children, including presence of fever. Minor symptoms such as congestion/rhinorrhea,
sore throat, cough and headache were also present more commonly in the non-hospitalized
cohort. As has been the case in adult reports, fewer than half of the patients had
both fever and respiratory symptoms present at the time of their diagnosis, but the
majorities have one or the other. Our critically ill cohort includes a previously
well child with the newly emerged hyper-inflammatory phenotype of SARS-CoV-2- associated
KD-like shock syndrome that has been identified concurrently within the same time
frame at other centers internationally. The pathogenesis of this phenotype is not
yet fully characterized but it is important to recognize as yet another potential
severe presentation in the pediatric population.
Co-infection with other viruses was distinctly uncommon in SARS-CoV-2 infected children
and young adults; 94% of those in whom this was assessed had no co-infection detected.
Of the 6% who had an additional virus detected, enterovirus/rhinovirus was responsible
for half, which is of unclear significance since enteroviruses are known to be shed
asymptomatically and detectable for months after initial infection. There was no association
between viral co-detection and severity of disease.
The reasons for the observed increased severity of disease in our pediatric and young
adult cohort requires additional detailed analysis, but potentially includes the comparatively
higher population density in our region compared with the Western United States and/or
the higher representation of African American race and/or Latino/Hispanic ethnicity
in our patient population, which has recently emerged as a risk factor for more severe
disease in adult populations. It recently has been noted that introduction of SARS-CoV-2
to the Eastern United States most likely occurred as a result of importation of European
strains, rather than Asian strains. Although no significant mutations conferring increased
pathogenicity have yet been described, this is another potential difference that merits
further analysis.
Limitations of this study include the retrospective design and the fact that transmission
is still ongoing at a steady rate of increase in our region, thus this represents
interim data, which will only be augmented further in the coming weeks. We plan to
address the role of race and ethnicity after validation of current administrative
data and have elected to defer this analysis until completed. One potential bias of
this study is our regional role in providing critical care for young adults age 21-35
years of age with COVID-19. However only two such hospitalized patients were present
in this study at the time of this interim report. Our study results would be expected
to be generalizable to other regions on the East Coast with similar patient populations
and population density, but may differ from other regions in the US that have yet
to experience expansion and surge of SARS-CoV2 cases, including rural areas.
In summary, our findings highlight the potential for severe disease in this age group
and inform other regions to anticipate and prepare their COVID-19 response to include
a significant burden of hospitalized and critically ill children and young adults.
As SARS-CoV-2 spreads within the United States, regional differences may be apparent
based on virus and host factors that are yet to be identified.