2. PATIENTS AND METHODS
Twenty-one pediatric patients with COVID‐19 infection confirmed by
clinical and laboratory findings from 20 February to 19 April, 2020 in
Children’s Hospital (Rasht/Iran) were included in this study. All the
patients are in accordance to the “Diagnosis and Treatment Protocol for
COVID‐19 (Fifth Revised Edition)” distributed by the National Health
Commission5. The protocol for this retrospective study
was approved by the Ethics Committee of Guilan University of Medical
Sciences (IR.GUMS.REC.1399.028). Then, demography information, clinical,
laboratory and radiological findings, and treatment strategies of
pediatrics patients with COVID‐19 were evaluated. The demography
information include contact history, previous history, travel history
over the last 2 weeks, contact history with the suspected person,
contact history with definite positive person, hospital visits or
hospitalizations history over the last month, influenza vaccine history,
routine vaccination history, underlying disease, using corticosteroid
over the last month, chemotherapy or immunosuppressive drugs over the
last 3 months, antibiotic consumption over the past two weeks, types of
antibiotics before administration. The hospital stays were updated to 20
June 2020. The chest computed tomography (CTs) was obtained from
majority of subjects. Two experienced pediatric radiologists reviewed
the CT images as some ground-glass opacities, consolidations with
surrounding halo sign, nodules, fine mesh shadow, pleural effusion,
lymphadenopathy, unilateral or bilateral, subpleural/non-subpleural, and
residual fiber strips. To confirm the existence of COVID‐19 RNA,
pharyngeal and nasopharyngeal swab samples of the subjects were
collected and identified by a reverse transcription, polymerase chain
reaction. All statistical analyses were performed using SPSS
(Statistical Package for the Social Sciences) version 13.0 software
(SPSS Inc). Categorical variables were described as frequency rates and
percentages, and continuous variables were described using median and
interquartile range (IQR) values. Normally distributed continuous
variables were presented as means with standard deviations (SD).
Comparison of the differences between the two groups was conducted using
the t -test or Chi-square test. Variables with a two-tailedP -value<0.05 were considered statistically significant.
RESULTS
Demography information
Out of 21 pediatric participants with COVID-19, 12 patients were young
males 12(57.1%) and nine patients were young girls 9(42.9%) (Table 1).
The mean age of pediatric patients with COVID-19 was 91.5±68.38 months
(Table 1). Four pediatric patients 4(19.4%) had an identified history
of close contact with suspected COVID-19-diagnosed family members. Five
pediatric patients 5(23.8%) had had a history of hospital visits or
hospitalizations over the last month. We demonstrated two pediatric
patients 2(9.5%) who had asthma and two pediatric patients 2(9.5%) who
had malignancy (Table 1).
clinical findingRegarding complications (Table 2), 11(52/3%) pediatric patients with
COVID-19 presented with tachypnea. Among all patients 4(19%) of them
developed tachycardia. However, two (9%) of them had bradycardia.
About, 2 (9.5%) of pediatric patients with COVID-19 suffered from
fatigue. Out of 21 pediatric patients, 8(38.1%) and 4(19%) patients
suffered from dry and wet cough, respectively. None of the patients
complained about sputum during coughing. Four out of 21(19%) patients
complained about diarrhea and nausea during the disease. This study
also showed that vomiting existed in 8 (38.1%) pediatric patients
with COVID-19 (Table 2). Most common symptoms in pediatric patients
with COVID-19 were fever 11(52.4%), cough 7(33.3%), weakness
5(23.8%), and discomfort in breathing 5(23.8%) (Table 2). On the
comorbidity, most patients suffered from the acute respiratory
distress syndrome (ARDS) and the acute kidney injury (AKI) as the ARDS
was shown in 3(14.3%) of pediatric patients with COVID-19 (Table 2).
Laboratory finding
The RT-PCR test was performed on 18 patients, which RT-PCR test results
was shown positive for 17 patients (81%) (Table 3). The mean value of
laboratory findings was estimated as follows; white-blood-cells (WBC)
count was 8460±6438×10⁹/L (Table 3). Six (30%) of patients suffered
from a decrease in white blood cells (Table 3). This study shows
lymphocytes and polymorph nuclear leukocytes (PMN) count were 28±1963
(×10 9/L), and 64±19.31 (×10⁹/L), respectively. In
this study, platelets count of pediatric patients with COVID-19 was
152290±78030.48 (×10⁹/L). The hemoglobin serum levels of pediatric
patients with COVID-19 was 12.33±5.54 (g/L). In addition, the mean value
of blood urea nitrogen (BUN) was 24±4796 (mg/dL). The creatinine levels
of serum were 0.97±0.99 (mg/dL). In addition, the serum electrolytes
levels including potassium (K), sodium (Na) and calcium (Ca) were
4.57±1.14 (mmol/L), 131.84±30.53 (mmol/L) and 8.55±1.56 (mg/dL),
respectively (Table 3). This study shows that coagulation screening
tests values were 14.55±1.46 (s) for prothrombin time (PT), and 37.5±9
(s) for partial thromboplastin time (PTT). The findings revealed that
the mean international normalized ratio (INR) was 1.26±0.21 pediatric
patients with COVID-19. Serum bilirubin levels were 0.9±0.84
(mg/dl) (direct bilirubin), and 1.65±0.77 (μmol/L) (total bilirubin).
Two (100) of patients suffered from direct bilirubin >0.2
(Table 3). Alanine aminotransferase (ALT) and aspartate transaminase
(AST) were 28.08±21.1 (U/L) and 46.33±24.21 (U/L), respectively (Table
3). The creatine phosphokinase (CPK) was 190.67±162.58 (units/L), and
the lactate dehydrogenase (LDH) was 698.71±336.18 (U/L) in pediatric
patients with COVID-19. In this study a decrease in CPK level was seen
in 1(33%) of patients (Table 3). Also 3 (42%) of patients had high
levels of LDH (Table 3). Regarding with arterial blood gas (ABG), statue
was exactly measured and recorded in pediatric patients with COVID-19.
Based on ABG findings; PH of pediatric patients with COVID-19 was
7.32±0.11, PaCo2 of patients was 38.91±8.57,
PaO2 was 72.80±28.92, and finally HCO3of patients was 20.52±5.17 (Table 3).
Radiology findings
Chest X-Ray
Chest x-ray (CXR) of five pediatric patients with COVID-19 (23.81%) out
of 21 patients who were included in this study showed
peripheral-airspace opacities (Table 4). The study showed that the CXR
in five pediatric patients with COVID-19 (23.81%) revealed ground-glass
opacity characterized by hazy-increased attenuation that did not obscure
bronchial and vascular margins of the lung (Table 4). As we showed in
Table 4, 7(33.33%) five pediatric patients with COVID-19 had lung
consolidations. A few of pleural effusions appeared in six (28.57%)
pediatric patients with COVID-19. This study also demonstrated that
4(19.05%) of the pediatric patients with COVID-19 had patchy
infiltrations. Meanwhile, cavitation was observed in four (19.05%) of
pediatric patients with COVID-19. In addition, 3(14.28%) of the
pediatric patients with COVID-19 showed extensive peripheral
lymphadenopathy (Table 4).
Lung CT scans
The most prevalent findings in lung CT scans were ground-glass opacity
and cavitations (66.66%) (Table 4). Whereas, nine CT scans (42.85%)
demonstrated a halo sign (Table 4). More than half of these patients
(57.14%) had peripheral-airspace opacities in lung CT scans. Ten
patients’ CT scans revealed pleural effusion (47.62%) (Table 4). Seven
patients’ CT scans (33.33%) revealed patchy infiltrations and bilateral
crazy paving pattern was revealed in nine CT scans (42.85%)(Table 4).
Eight CT scans (38.09%) showed peripheral lymphadenopathy White lung
appearance. Centro lobular nodule were observed in six patients.
(28.57%). Lung consolidation and revers halo sign appearance were less
common with the incidence of 28.7% and 14.28% respectively (Table 4).
Treatment strategiesThis study showed that nine pediatric patients 9(57.1%) had a history
of antibiotics consumption over the past two weeks (Table 5). In the
treatment of pediatric patients with COVID-19, chloroquine,
oseltamivir and Kaletra (Lopinavir / Ritonavir) were used in
8(38.1%), 8(38.1%) and 6(28.6%), respectively (Table 5). This study
shows that 95.2% of pediatric patients with COVID-19 took antibiotics
repeatedly. During the treatment of pediatric patients with COVID-19,
2(9.5), 5(23.8), 3(14.33), 1(4.8) and 1(4.8) of patients consumed
azithromycin ceftriaxone, vancomycin, ceftriaxone, clindamycin,
ceftriaxone, vancomycin, ceftriaxone and azithromycin, respectively
(Table 5). Based on the results of our study, 6(28.6%), 2(9.5%) and
2(9.5%) of pediatric patients with COVID-19 were treated by oxygen
with mask, oxygen with hood and intubation, respectively (Table 5). In
current study, 4(19.04%) pediatric patients with COVID-19 died and
17(80.95%) patients were discharged from the hospital. One of the
patients who died suffered from acute respiratory distress syndrome
(ARDS).
Discussion
COVID‐19 viral pneumonia is an acute respiratory infectious disease
caused by the novel coronavirus (SARS-CoV-2). The onset of the COVID-19
could be asymptomatic (4%), but often as a mild-upper respiratory viral
illness (51%), with a lower incidence of pneumonia (39%) and rarely
severe cases such as hypoxia, respiratory distress (5%), occurs as ARDS
or multi-organ involvement (<1%)6. Because
the clinical presentation of pediatric patients with COVID-19 is vague
or similar to some respiratory infections, it is essential for
pediatricians to have more information and also consider
COVID-197. In this study, with the mentioned aim,
demographic, clinical, para clinical and imaging information, treatment
and its results in hospitalized children with definite and probable
diagnosis of COVID-19 were reviewed.
As we found out in this study, the COVID-19 was more common in
school-age infants and toddlers (Table 1). We realized that the COVID-19
was also more common in young males, which may indicate that young males
at school are more exposed to the COVID-19 and are more likely to be
infected with COVID-19. We believe that the age of the pediatrics plays
an important role in the incidence of COVID-19. This means that older
pediatrics have more social contact with other people and are more
likely to develop COVID-19. Huan Wu and colleagues found that common
large gender of pediatric patients with COVID-19 (59.5 %) were of the
young girls8. Ansel Hoang and colleagues came to
realize that 55.6% of COVID-19 children were males 9.
Remarkably, out of 21 patients 12 had a previous history of contact with
COVID‐19 infection. In other words, about 50% of pediatric patients
with COVID-19 had no previous contact history, which may indicate that
pediatric patients with no history of contact may be susceptible to
COVID‐19 infection. Ansel Hoang and colleagues found that 75.6% of
pediatric patients with COVID-19 exposure were infected via family
members9. In addition, eight out of 21 patients had a
previous history of congenital or acquired diseases, which may indicate
that pediatrics with underlying diseases such as asthma and malignancy
may be more prone to more severe COVID‐19 infection. Ansel Hoang and
colleagues found that immunocompromised pediatrics (30.5 %) or
pediatrics with respiratory (21.0 %), cardiac disease (13.7%)
comprised the largest subset of COVID-19 pediatrics with underlying
disease9. This study showed that fever, dyspnea or
rapid breathing, cough and nausea and vomiting were the most common and
the main complaints of pediatric patients with COVID-19. Our study
focused on the more severe COVID-19 of hospitalized patients. This study
is not comparable to asymptomatic or milder cases of COVID-19, because
asymptomatic or milder patients are not hospitalized. The most common
symptoms in pediatric patients with COVID-19 were fever (40.5%), dry
cough (44.6%), vomiting or diarrhea (21.6%), and headache (3.4%)8. Ansel Hoang and colleagues found that fever
(71.4%), cough (57.1%), and dyspnea (28.6%) comprised the largest
clinical characteristics among children with COVID-19 disease9. Also, this study showed that fever, cough, dyspnea
and weakness were the most common symptoms in pediatric patients with
COVID-19. Ansel Hoang and colleagues found that the most common symptoms
in pediatric patients with COVID-19 were asymptomatic (19.3%), fever
(59.1%), cough (55.9%), myalgia, fatigue (18.7%), sore throat
(18.2%), shortness of breath, dyspnea (11.7%), abdominal pain,
diarrhea (6.5%), and rhinorrhea, nasal congestion (20.0%)9. The most common clinical signs on examination were
fever 11(52.4%), cough 7(33.3%), weakness and lethargy 5(23.8%), and
discomfort in breathing 5(23.8%). At present, there is no certain
antiviral drug for covid19 virus treatment in children. However, some
antiviral and anti-inflammatory agents may have clinically useful
effects in reducing the manifestations of covid19 virus due to
overresponse of immune system through interleukins and other
inflammatory agents releasing10,11. Chloroquine as a
potential pharmacologic agent against covid19 has immunomodulatory
effects by inflammatory cytokines inhibition 12 In
this study, 38.1% of pediatric patients with COVID-19 were treated by
chloroquine. Combination Ritonavir with Lopinavir improved patients’
symptoms and reduced the need for intensive care unit in severe
cases13.28.6% were treated by Kaletra:Lopinavir
/Ritonavir, and 38.1% were treated by oseltamivir. There is no exact
evidence for efficacy of these drugs above. In this study, 14.33%of
pediatric patients with COVID-19 received vancomycin and ceftriaxone
during treatment. 23.8% recieved ceftriaxone. 14.33% of pediatric
patients with COVID-19 received vancomycin and ceftriaxone. Oxygen with
masks was used in 28.6% of pediatric patients with COVID-19. 4.8% of
pediatric patients with COVID-19 also used oxygen with hood intubation.
In current study, 4(19.04%) pediatric patients with COVID-19 died and
17(80.95%) patients were discharged from the hospital. One of the
patients who died suffered from ARDS.
Conclusion
We found out that pediatrics, especially boys are more susceptible to
COVID‐19 and it is more common in school-age and toddlers.
Manifestations are milder than adults and severe cases associated with
underlying disease. The effectiveness of drugs in the treatment of this
disease needs further study.