Clinical and epidemiological features of Children with COVID 19

1. Clinicaland
epidemiologicalfeaturesof
Childrenwithcoronavirus
disease2019(COVID-19)
Ramin Nazari, MD, FAAP, FCCM
Assistant Professor of Pediatric at UCF
COM
March 2020

2. INTRODUCTION
● Coronaviruses are important human and animal pathogens.
● At the end of 2019, a novel coronavirus was identified as the cause of a cluster
of pneumonia cases in Wuhan, China.
● It rapidly spread, resulting in an epidemic throughout China, followed by an
increasing number of cases in other countries throughout the world.
● In February 2020, the WHO designated the disease COVID-19.
● The virus that causes COVID-19 is designated severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV.

3. Virology
● COVID-19 is a betacoronavirus in the same subgenus as the (SARS) virus (as well
as several bat coronaviruses), but in a different clade.
● The structure of the receptor-binding gene region is very similar to that of the
SARS coronavirus, and the virus has been shown to use the same receptor, the
ACE2, for cell entry.

4. EPIDEMIOLOGY
● Geographic distribution — Globally, >685,000 confirmed cases of COVID-19 with
>32,000 deaths have been reported.( March 29th)
● Route of transmission: The virus that causes COVID-19 probably emerged from an
animal source,
○ But is now spreading from person to person which is thought to occur mainly
via respiratory droplets.
○ Infection can also occur if a person touches an infected surface and then
touches his or her eyes, nose, or mouth.
○ Droplets typically do not travel more than six feet (2 meters) and do not linger
in the air; however, there are evidence that remained viable in aerosols under
experimental conditions for at least three hours.
○ Given the current uncertainty, airborne precautions are recommended routinely
in some countries and in the setting of certain high-risk procedures in

5. ○ SARS-CoV-2 RNA has been detected in blood and stool specimens, but according to a
joint WHO-China report, fecal-oral transmission did not appear to be a significant factor
in the spread of infection
● Period of infectivity — The interval during which an individual with COVID-19 is infectious is
uncertain.
○ Viral RNA levels appear to be higher soon after symptom onset compared with later in
the illness ; this raises the possibility that transmission might be more likely in the earlier
stage of infection.
○ The duration of viral shedding is also variable;
○ There appears to be a wide range, which may depend on severity of illness.
○ In one study of 21 patients with mild illness (no hypoxia),10 days after the onset of
symptoms;, In another study of 137 patients who survived COVID-19, the median duration
of viral RNA shedding from oropharyngeal specimens was 20 days
EPIDEMIOLOGY

6. ● The reported rates of transmission from an individual with symptomatic
infection vary by location and infection control interventions.
● According to a joint WHO-China report, the rate of secondary COVID-19
ranged from 1 to 5 percent among tens of thousands of close contacts of
confirmed patients in China .
● Among crew members on a cruise ship, 2 percent developed confirmed
infection .
● In the United States, the symptomatic secondary attack rate was 0.45
percent among 445 close contacts of 10 confirmed patients.
● Transmission of SARS-CoV-2 from asymptomatic individuals (or within the
incubation period) has also been described. However, the extent to which
this occurs remains unknown
EPIDEMIOLOGY-Periodofinfectivity:

7. ● Immunity — Antibodies(Abs) to the virus are induced in those who have become infected.
○ Preliminary evidence suggests that some of these Abs are protective.
○ Moreover, it is unknown whether all infected patients mount a protective immune response and
how long any protective effect will last.
○ Data on protective immunity following COVID-19 are emerging but still in very early stages.
○ One study derived monoclonal antibodies from convalescent patients' B-cells that targeted the
receptor-binding domain of the spike protein and had neutralizing activity in a pseudovirus
model.
○ However, neither of these studies has been published in a peer reviewed journal, and further
confirmation of these findings is needed.
EPIDEMIOLOGY

8. CLINICALFEATURES
● Incubation period :
○ within 14 days following exposure, with most cases occurring approximately four to
five days after exposure.
○ In a study of 1099 patients with confirmed symptomatic COVID-19, the median
incubation period was four days].
○ Using data from 181 publicly reported, confirmed cases in China with identifiable
exposure, one modeling study estimated that symptoms would develop in 2.5
percent of infected individuals within 2.2 days and in 97.5 percent of infected
individuals within 11.5 days. The median incubation period in this study was 5.1 days.

9. ● Mild (no or mild pneumonia) was reported in 81 percent.
● Severe disease (eg, with dyspnea, hypoxia, or >50 percent lung involvement on imaging within
24 to 48 hours) was reported in 14 percent.
● Critical disease (eg, with respiratory failure, shock, or multiorgan dysfunction) was reported in 5
percent.
● The overall case fatality rate was 2.3 %; no deaths were reported among noncritical cases.
● Joint WHO-China fact-finding mission, the case-fatality rate ranged from 5.8% in Wuhan to 0.7
% in the rest of China. Most of the fatal cases occurred in patients with advanced age or
underlying medical comorbidities.
● The proportion of severe or fatal infections may vary by location. in Italy, 12% of all detected
COVID-19 cases and 16 % of all hospitalized patients were admitted to the ICU; the estimated
case fatality rate was 7.2% in mid-March.
● In contrast, the estimated case fatality rate in mid-March in South Korea was 0.9%. This may be
related to distinct demographics of infection; in Italy, the median age of patients with infection
was 64 years, whereas in Korea the median age was in the 40s.
CLINICALFEATURES-Spectrumofillnessseverity

10. ● Severe illness can occur in otherwise healthy individuals of any age, but it predominantly
occurs in adults with advanced age or underlying medical comorbidities.
● Comorbidities that have been associated with severe illness and mortality include:
○ Cardiovascular disease
○ Diabetes mellitus
○ Hypertension
○ Chronic lung disease
○ Cancer
○ Chronic kidney disease
● In a subset of 355 patients who died with COVID-19 in Italy, the mean number of pre-
existing comorbidities was 2.7, and only 3 patients had no underlying condition [43].
CLINICALFEATURES-Riskfactorsforsevereillness

11. ● Particular lab features have also been associated with worse outcomes:
● Lymphopenia
● Elevated liver enzymes
● Elevated lactate dehydrogenase (LDH)
● Elevated inflammatory markers (eg, C-reactive protein [CRP], ferritin)
● Elevated D-dimer (>1 mcg/mL)
● Elevated prothrombin time (PT)
● Elevated troponin
● Elevated creatine phosphokinase (CPK)
● Acute kidney injury
CLINICALFEATURES-laboratoryfeatures

12. ● Individuals of any age can acquire (SARS-CoV-2) infection.
● In several cohorts of hospitalized patients with confirmed COVID-19, the median
age ranged from 49 to 56 years.
● In a report from the Chinese CDC and Prevention that included approximately
44,500 confirmed infections, 87% of patients were between 30 and 79 years old .
● Older age associated with increased mortality, with case fatality rates of 8 and 15%
among those aged 70 to 79 years and 80 years or older, respectively.
● Similar findings from Italy, with case fatality rates of 12 and 20% among those aged
70 to 79 years and 80 years or older, respectively.
● In the United States, 2449 patients diagnosed with COVID-19 between February 12
and March 16, 2020 had age, hospitalization, and ICU information available ; 67% of
cases were diagnosed in those aged ≥45 years, and, similar to China, MR was
highest among olders, with 80 % of deaths occurring in those aged ≥65 years.
CLINICALFEATURES-Impactofage:

13. ● Clinical manifestations
● Initial presentation — Pneumonia appears to be the most frequent serious
manifestation of infection, characterized primarily by fever, cough, dyspnea,
and bilateral infiltrates on chest imaging.
● No specific clinical features that can yet reliably distinguish COVID-19 from
other viral respiratory infections.
● In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the
most common clinical features at the onset of illness were :
● Fever in 99 %
● Fatigue in 70 %
● Dry cough in 59 %
● Anorexia in 40 %
● Myalgias in 35 %
● Dyspnea in 31 %
● Sputum production in 27 %
CLINICALFEATURES

14. Clinical and epidemiological features of
Children
with coronavirus disease 2019 (COVID-19)

15. InGeneral
● Symptomatic infection in children appears to be uncommon;
● when it occurs, it is usually mild, although severe cases have been reported.
● In the large Chinese report, only 2% of infections were in individuals younger
than 20 years old
● Similarly, in South Korea, only 6.3% of nearly 8000 infections were in those
younger than 20 years old.

17. ● Children are less likely to become severely ill than older adults
● There are subpopulations of children with an increased risk for more significant
illness.
● One viral surveillance study in a PICU in China reported that coronavirus was
detected in more children with ARDS than human metapneumovirus.
● Another study in hospitalized Norwegian children detected coronaviruses in
10% of hospitalized children with respiratory tract infections.
● Younger age, underlying pulmonary pathology, and immunocompromising
conditions have been associated with more severe outcomes with nonCOVID-19
coronavirus infections in children.

18. ● Prior studies have shown that children from whom coronaviruses are detected
from the respiratory tract can have viral co-infections in up to two-thirds of
cases.
● Children without virologic confirmation were more likely to have severe disease
than children from whom COVID-19 was detected, potentially because their
symptoms were caused by other pathogens.

19. ● Children may play a major role in community-based viral transmission.
● Available data suggest that children may have more upper respiratory tract
(including nasopharyngeal carriage), rather than lower respiratory tract
involvement.
● There is also evidence of fecal shedding in the stool for several weeks after
diagnosis, leading to concern about fecal-oral transmission of the virus,
particularly for infants and children who are not toilet-trained, and for viral
replication in the gastrointestinal tract.
● Prolonged shedding in nasal secretions and stool has substantial implications for
community spread in daycare centers, schools, and in the home.

20. ● Non-COVID-19 coronaviruses are detectable in respiratory secretions in a large
percentage of healthy children, and the extent to which this is also seen in
COVID-19 is unclear.
● Prolonged viral shedding in symptomatic individuals, combined with
shedding in asymptomatic persons, would render contact tracing and other
public health measures to mitigate spread less effective.
● While vertical transmission has not yet been reported,11 many of the infants
born to COVID-19-infected mothers were delivered surgically and quickly
separated from their mothers.

21. ● Widespread availability of testing will allow for us to more accurately
describe the spectrum of illness and may result in adjustment of the
apparent morbidity and mortality rate as fewer ill individuals are
diagnosed.

23. Results
● By Feb 8, 2020, 2143 pediatric patients with COVID-19 were reported to China CDC
○ 731 (34.1 %) laboratory-confirmed cases
○ 1412 (65.9 %) were suspected cases
○ The median age of all patients was 7 years (Interquartile range: 2-13).
○ 1213 cases (56.6 %) were boys(no statistically significant difference in the number of pediatric
patients between boys and girls).
○ Severity:(both confirmed and suspected cases),
■ Asymptomatic 94 (4.4 %)
■ Mild 1091 (50.9 %)
■ Moderate 831 (38.8 %)
○ totally accounted for 94.1 % of all cases.

24. ● Severity of illness by age reveals that young children, particularly infants, were
vulnerable to 2019-nCoV infection.
● The proportion of severe and critical cases was
○ <1 y: 10.6 %
○ 1-5 y: 7.3%,
○ 6-10 y: 4.2%,
○ 11-15 y: 4.1% and
○ >16 y: 3.0%
○ a 14-year-old boy died on Feb 7, 2020
Results

25. Results
● Among the 2143 pediatric patients, there was a trend of the rapid increase of
disease onset in the early stage of the epidemic, and then, a gradual and steady
decrease (Fig 1).
● The earliest date of illness onset was Dec 26, 2019, while the earliest date of
diagnoses was Jan 20, 2020.
● The median days from illness onset to diagnoses was 2 days (range: 0 to 42
days).
● Most cases were diagnosed in the 1st week after illness onset occurred
● Compared with the adults’ cases, the severity of children’s COVID-19 cases was
milder, and the case fatality rate was much lower.

26. Conclusions
● Children at all ages were sensitive to COVID-19, and there was no significant
gender difference.
● Clinical manifestations of children’s COVID-19 cases were less severe than those
of adults’ patients.
● However, young children, particularly infants, were vulnerable to 2019-nCoV
infection.
● The distribution of children’s COVID-19 cases varied with time and space.,
● Furthermore, the results of this study provide strong evidence for human-to-
human transmission as children were unlikely to visit the Huanan Seafood
Wholesale Market where the early adult patients were reported to obtain 2019-
nCoV.

47. Thank you