Clinico-Epidemiological Characteristics of Pediatric COVID-19 Patients in Bangladesh

Abstract

Background
To delineate the clinico-epidemiological characteristics of pediatric coronavirus disease-2019 (COVID-19) patients was the objective of the study.

Method
This observational study included 290 pediatric patients with a definite diagnosis of COVID-19 admitted to Dhaka Shishu Hospital, Bangladesh, from April 2021 to October 2021. Clinical and epidemiological characteristics were analyzed based on demographic data, medical history, laboratory tests, and outcome information. Data analysis was performed with SPSS 26. Ethical measures were taken in compliance with the current declaration of Helsinki, and final analysis was performed using SPSS 26.

Result
Of all, 42 (14.5%) were neonates (< 28 days), 88 (30.3%) were infants (28 days to < 1 year) and 160 (55.2%) were children (1–17 years). The median age of the children was 18 (0.3–204) months, 58.3% were male, 62% had malnutrition, and presented with various clinical presentations. The main symptoms were fever (5.7%) and breathlessness (20%). Approximately 22% of children were asymptomatic, and 57% had at least one comorbidity. Fever and abdominal pain were predominant presenting symptoms in children compared with neonates and infants (p < .01 for both), while cough and breathlessness were more frequent in infants (p < .01 for both). The infants suffered significantly from neutropenia and lymphocytosis than neonates and children (p < .001 for both). The discharge and death rates were 77.8% with 6.9%. Overall case fatality was higher among neonates than others.

Conclusion
Compared to other pediatric groups, neonatal case fatality was higher, and COVID-19 in neonates, infants, and children has similar epidemiological and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic of these particular age groups.

Full text

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Clinico-Epidemiological Characteristics of Pediatric
COVID-19 Patients in Bangladesh
Probir Kumar Sarkar
Dhaka Shishu (Children) Hospital
Kinkar Ghosh
Dhaka Shishu (Children) Hospital
Dr Reaz Mobarak
Dhaka Shishu (Children) Hospital
Md Kamruzzaman
Dhaka Shishu (Children) Hospital
Rizwanul Ahsan
Dhaka shishu (Children) Hospital
Dr Shireen Afroz
Dhaka Shishu (Children) Hospital
Maksudur Rahman
Dhaka Shishu (Children) Hospital
Nabila Akand
Dhaka Shishu (Children) Hospital
Nahid Farzana
Dhaka Shishu (Children) Hospital
Shah Ali Akbar Ashra
Dhaka Shishu (Children) Hospital
Maleeha Sheefa
World Health Organization: Bangladesh Oce
Nurun Nahar
Dhaka Shishu (Children) Hospital
Dr Syed Sha Ahmed
Dhaka Shishu (Children) Hospital
Sheikh Wasik Rahman
Child Health Research Foundation
Anjim Macsud
Pi Research Consultancy Center
Mohammad Jahid Hasan (  dr.jahid61@gmail.com )
Pi Research Consultancy Center https://orcid.org/0000-0001-9212-1739
Research Article

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Keywords: Children, COVID-19, Pandemic, Neonate, Infants, Clinical manifestations
DOI: https://doi.org/10.21203/rs.3.rs-591093/v1
License:   This work is licensed under a Creative Commons Attribution 4.0 International License.  Read Full
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Abstract
Background
To delineate the clinico-epidemiological characteristics of pediatric coronavirus disease-2019 (COVID-19)
patients was the objective of the study.
Method:
This observational study included 290 pediatric patients with a denite diagnosis of COVID-19 admitted to
Dhaka Shishu Hospital, Bangladesh, from April 2021 to October 2021. Clinical and epidemiological
characteristics were analyzed based on demographic data, medical history, laboratory tests, and outcome
information. Data analysis was performed with SPSS 26. Ethical measures were taken in compliance with the
current declaration of Helsinki, and nal analysis was performed using SPSS 26.
Result
Of all, 42 (14.5%) were neonates (< 28 days), 88 (30.3%) were infants (28 days to < 1 year) and 160 (55.2%)
were children (1–17 years). The median age of the children was 18 (0.3–204) months, 58.3% were male, 62%
had malnutrition, and presented with various clinical presentations. The main symptoms were fever (5.7%) and
breathlessness (20%). Approximately 22% of children were asymptomatic, and 57% had at least one
comorbidity. Fever and abdominal pain were predominant presenting symptoms in children compared with
neonates and infants (p < .01 for both), while cough and breathlessness were more frequent in infants (p < .01
for both). The infants suffered signicantly from neutropenia and lymphocytosis than neonates and children
(p < .001 for both). The discharge and death rates were 77.8% with 6.9%. Overall case fatality was higher
among neonates than others.
Conclusion
Compared to other pediatric groups, neonatal case fatality was higher, and COVID-19 in neonates, infants, and
children has similar epidemiological and clinical manifestations. The ndings from this study might help to
guide the development of measures to prevent and treat this ongoing global pandemic of these particular age
groups.
1. Background:
Since December 2019, an outbreak of undiagnosed pneumonia cases with presumptive viral origin started in
Wuhan, China, and began to spread rapidly throughout the world [1]. At the beginning of 2020, the International
Committee on Taxonomy of Viruses denominated this new virus severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) [2]. The World Health Organization (WHO) designates this pandemic disease as coronavirus
disease 2019 (COVID-19) [2–4] and later declares a public health emergency of international concern [5]. To
date, over 140million patients have been diagnosed with COVID-19 globally [6]. The cumulative number of

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laboratory-conrmed cases has been reported to be over 700,000, and more than 10,000 reported deaths [7].
The clinical spectrum of COVID-19 is wide, varying from completely asymptomatic forms to those
characterized by severe respiratory distress requiring intensive care resulting in death [8–10]. All ages are
susceptible to this infection. However, the number of conrmed cases in children with COVID-19 is relatively
small; hence, very limited information is available compared to adults [11, 12]. One of the largest surveys
revealed that 2.2% [13] of children were affected in China, while in the USA, the number was 1.7% [14]. The
exact prevalence of COVID-19 among Bangladeshi children is still lacking.
Ample evidence suggests that compared to adults, children with COVID-19 have distinct epidemiological and
clinical manifestations [15]. For example, when adult patients predominantly present with fever, cough,
breathlessness, sore throat, and headache, children present with cough, pharyngitis, fever, diarrhea, vomiting,
and a negligible amount of gustatory and olfactory symptoms [16–18]. In addition, there are fewer severe
cases than adults [17, 19, 20]. Most likely, therefore, very limited comprehensive guidelines are available
focusing on the management of COVID-19 in children rather than adults [16]. However, understanding the
clinical manifestation of the pediatric population and their variation in different age groups, including neonates
(< 28 days), infants (28 days to < 1 year), and children (1 year to < 18 years), is important for clinical and
containment strategies. Considering the lack of detailed epidemiological information of pediatric patients, we
conducted an observational study to record epidemiological and clinical features and outcome data up to
discharge among the different pediatric populations (neonates, infants, and children < 18 years) admitted to
Dhaka Shishu Hospital, Bangladesh.
2. Methods;
2.1 Study design and participants:
This observational study was approved by the institutional review board (IRB) of Dhaka Shishu Hospital (DSH),
Dhaka, Bangladesh [ethical approval no. 651(1)/DSH/2020)]. Children admitted to the hospital with clinical
features consistent with COVID-19 were initially quarantined prior to SARS-CoV-2 nucleic acid detection [21].
Bed-sided nasopharyngeal swab of suspected patients was collected using a swab stick by a skilled health
care worker for RT-PCR. Suspected COVID-19 cases were dened as the presence of at least one clinical
manifestation: fever, breathlessness, tachypnea, lethargy, poor feeding, cough, vomiting, diarrhea, sore throat, or
runny nose during admission. A reverse transcriptase-polymerase chain reaction (RT-PCR) test was performed
for all suspected cases with the samples collected from the respiratory tract. Laboratory-conrmed [positive RT-
PCR (qualitative) for SARS-CoV-2] cases were nally included within the period spanning from May 2020 to
December 2020. Parents who did not provide consent to participate in the study refrained from inclusion.
Assessment of the children and management was ensured according to the recommendation of the National
Guidelines on Clinical Management of COVID-19 [22] and interim guidance provided by the Bangladesh
Pediatric Association (BPA). Details of the patient selection are available in supplementary Fig.1.
Data collection procedure:
A preformed questionnaire was prepared based on published literature and was piloted among 15 cases
admitted to DSH. Experiences from the piloting were adjusted during the nalization of the questionnaire. The

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medical records of the included patients were accessed by the study research physicians. Prior to data
collection, all of the research physicians (a total number of four) were trained for data collection and clinical
record assessment. Clinical data were extracted, including demographic data, clinical symptoms, signs,
comorbidities, and laboratory ndings. Nutritional assessments were also performed by a growth monitoring
promotion (GMP) card. Mid upper arm circumference (MUAC) tape was used during the assessment of mid
upper arm circumference (MUAC), and body weights of neonates and infants were measured with WS590 -
Baby Weighing Scales. For children aged more than 1 year, a digital body weight measuring scale was used. All
patients were managed by standard care for COVID-19. Comorbidities were also managed based on the
diagnosis and treatment protocol of the disease. All patients were followed-up to the discharge. The outcome
was dened as recovery, death, referred to the superspecialized center, and left the hospital against advice. The
discharge criteria followed in the study were as follows: normal body temperature or no fever for at least three
consecutive days; alleviation of upper respiratory symptoms (in comparison to the admission day); and
negative RT-PCR (qualitative) results obtained for SARS-CoV-2 nucleic acid detection at day 14 (from the index
test). Written informed consent was provided by their parents or guardians before data collection.
Quality assurance of the data and reporting guidelines
The principal investigator and/or his team supervised the data collection procedures and randomly cross-
checked the collected data to ensure quality control. In case of any breach of the standard procedure observed,
the investigator team communicated with the research physicians and attending doctors to maintain the
standard care and data collection process. After completion of the data collection, all data were sorted and
stratied into three groups based on the age difference. Here, neonates were considered age less than 28 days,
infants less than 1 year, and children between 1 year and < 18 years of age.
Statistical analyses:
Statistical analyses were conducted using SPSS software (version 26, IBM statistics). Missing values were
managed by subtracting the data from the nal data set. No mean imputation was made. Continuous data are
expressed as the mean ± standard deviation or median (range), while categorical data are presented as a
number, frequency, or percentage. Both parametric and nonparametric tests were used whenever necessary. The
results are expressed with 95% condence intervals (CIs), and a p-value < .05 was considered statistically
signicant.
3. Results:
A total of 290 pediatric patients with COVID-19 were included in the study. The median age of the patients was
18 months, with a range between 1 day and 17 years. Of all, 42 (14.5%) were neonates, 88 (30.3%) were infants
and 160 (55.2%) were children. More than half of the pediatric patients were male (58.3%). Among all 73
(45.3%), 26 (16.1%) and 1 (0.6%) had severe malnutrition, moderate malnutrition and overnutrition, respectively.
Nearly half of the pediatric patients (n = 146, 50.3%) had at least one comorbidity, and 20 (6.9%) had more than
one comorbidity. Single comorbidities were signicantly more common among children than neonates and
infants, while more than one comorbidity was signicantly more common among neonates (p < 0.001)
(Table1). A detailed list of comorbidities found among the pediatric patients is presented in supplementary

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table 1. Acute leukemia and nephrotic syndrome were the comorbidities found in a signicantly higher
proportion in children (p < 0.05).
Table 1
Demographic characteristics, nutritional status and comorbidities of pediatric patients with COVID-19 (n =
290)
Variable Total
n (%)
Neonate
n(%)
Infant
n (%)
Children
n (%)
p-value
Number 290 42 (14.5) 88 (30.3) 160 (55.2) 
Age (months)     
Median 18 (0.3–204) 0.25 (0.03–0.87) 6 (0.97-12.00) 64 (13–204) 
Sex     
Male 169 (58.3) 27 (64.3) 53 (60.2) 89 (55.6) 0.542
Female 121 (41.7) 15 (35.7) 35 (39.8) 71 (44.4) 
Weight (kg)     
Mean ± SD 7.61 ± 4.63 2.84 ± 0.49 5.73 ± 2.07 12.28 ± 3.67 
Nutritional Status*     
Normal 61 (37.9) 12 (35.3) 23 (33.3) 26 (44.8) 0.448
Severe malnutrition 73 (45.3) 17 (50.0) 36 (52.2) 20 (34.5) 
Moderate malnutrition 26 (16.1) 5 (14.7) 10 (14.5) 11 (19.0) 
Overnutrition 1 (0.6) 0 0 1 (1.7) 
Number of comorbidities     
One 146 (50.3) 5 (11.9) 37 (42.0) 104 (65.0) < 0.001
More than one 20 (6.9) 1 (24) 7 (8.0) 12 (7.5) 
None 124 (42.8) 36 (85.7) 44 (50.0) 44 (27.5) 
p
-
value determined by Chi-square test
*Excluding 129 missing values
The common clinical presentation was fever (n = 150, 51.7%), followed by breathlessness (n = 58, 20.0%),
abdominal pain (n = 48, 16.6%), cough (n = 42, 14.5%), seizure (n = 37, 12.8%), and vomiting (n = 36, 12.4%),
among others. Fever, abdominal pain, vomiting, rash, and weakness were signicantly more common among
children (p < 0.05). Breathlessness, cough, seizure, and vomiting were signicantly more common among
infants (p < 0.05) (Table2).

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Table 2
Clinical presentation of pediatric patients with COVID-19 (n = 290)
Variable Total
n (%)
Neonate
n (%)
Infant
n (%)
Children
n (%)
p-value
 (n = 290) (n = 42) (n = 88) (n = 160) 
Asymptomatic 65 (22.4) 35 (83.3) 13 (14.8) 17 (10.6) < 0.001
Fever 150 (51.7) 5 (11.9) 47 (53.4) 98 (61.3) < 0.001
Breathlessness 58 (20.0) 4 (9.5) 33 (37.5) 21 (13.1) < 0.001
Abdominal pain 48 (16.6) 0 11 (12.5) 37 (23.1) 0.001
Cough 42 (14.5) 1 (2.4) 22 (25.0) 19 (11.9) 0.001
Seizure 37 (12.8) 3 (7.1) 15 (17.0) 19 (11.9) 0.268
Vomiting 36 (12.4) 0 9 (10.2) 27 (16.9) 0.009
Sepsis 17 (5.9) 5 (11.9) 7 (8.0) 5 (3.1) 0.059
Oedema 16 (5.5) 1 (2.4) 4 (4.5) 11 (6.9) 0.487
Loose motion 14 (4.8) 0 7 (8.0) 7 (4.4) 0.138
Rash 13 (4.5) 0 1 (1.1) 12 (7.5) 0.023
Seizure 12 (4.1) 0 5 (5.7) 7 (4.4) 0.321
Feeding problem 11 (3.8) 0 6 (6.8) 5 (3.1) 0.147
Weakness 9 (3.1) 0 0 9 (5.6) 0.021
Sore throat 3 (1.0) 0 0 3 (1.9) 0.722
Runny nose 2 (0.7) 0 1 (1.1) 1 (0.6) 1.000
Unconsciousness 2 (0.7) 0 1 (1.1) 1 (0.6) 1.000
Delayed Cry 2 (0.7) 2 (4.8) 0 0 0.021
Local Swelling 1 (0.3) 0 0 1 (0.6) 1.000
*p
-
value determined by Chi-square test
Table3 describes the investigation prole of the pediatric patients with COVID-19. The average hemoglobin
level was 10.95 ± 2.78 g/dl (SD), with a signicantly higher level among neonates than infants and children (p <
0.001). The average hematocrit was 34.54 ± 9.72% (SD), with a signicantly higher value in neonates than in
infants and children (p < 0.001). The median WBC count was 11.20 x 103/mm3, ranging from 0.01 to 127.80 x
103/mm3, with children having a signicantly lower WBC count than neonates and infants (p < 0.001). The
percentage of neutrophils was signicantly lower and lymphocytes was signicantly higher among infants
than among neonates and children (p < 0.001). The median platelet count among pediatric patients was 2.80 x
106/mm3, with a signicantly higher median value among infants than neonates and children (p < 0.001).
Serum creatinine was signicantly higher among neonates than among infants and children (p = 0.002).

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Table 3
Investigation prole of pediatric patients with COVID-19 (n = 290)
Investigation Total
Mean ± SD
Neonate
Mean ± SD
Infant
Mean ± SD
Children
Mean ± SD
p-
value
Hemoglobin (g/dl) 10.95 ± 2.78 14.64 ± 3.02 10.46 ± 1.75* 10.28 ± 2.45* <
0.001
Hematocrit (%) 34.54 ± 9.72 46.71 ± 10.10 33.43 ± 6.77* 32.07 ± 8.69* <
0.001
RBC (x 106/mm3)4.23 ± 0.95 4.42 ± 0.90 4.19 ± 0.77 4.04 ± 1.03 0.087
WBC (x 103 /mm3)11.20 (0.01–
127.80) 12.50 (3.80–
37.10) 12.30 (0.01–
126.00) 10.10 (1.10–
127.80)*!
0.001
Neutrophil (%) 53.00 (3.00–
91.00) 59.00 (17.00–
89.00) 38 (9.00–
85.00)* 54.50 (3.00–
91.00)!
<
0.001
Lymphocyte (%) 41.00 (6.00–
95.00) 31 (6.00–
72.00) 51.50 (10.00–
84.00)* 38.50 (7.00–
95.00)!
<
0.001
Monocyte (%) 5.00 (0–34.00) 6 (0–13.00) 6 (0–12.00) 4.00 (0–34.00)!0.004
Eosinophil (%) 1.00 (0–17.00) 1.00 (0–7.00) 1.00 (0–17.00) 1.00 (0–16.00) 0.933
Platelet (x
106/mm3)
2.80 (0.12–
8.06) 2.52 (0.24–
6.76) 3.70 (0.22–
8.06)* 2.57 (0.12–
7.76)!
<
0.001
Serum creatinine
(mg/dl) 0.49 (0.01–
10.71) 0.84 (0.33–
5.11) 0.42 (0.01–
5.72)* 0.50 (0.03–
10.71)* 0.002
Sodium (mmol/l) 141.38 ± 5.59 142.56 ± 6.49 140.88 ± 5.11 141.279 ± 5.53 0.371
Potassium
(mmol/l) 4.52 ± 1.04 5.28 ± 1.29 4.83 ± 0.97 4.13 ± 0.77*!<
0.001
Chloride (mmol/l) 102.29 ± 12.25 101.73 ± 14.37 103.76 ± 8.29 101.70 ± 13.28 0.571
Data is expressed as mean ± SD or median (min-max).
P-value determined by ANOVA and Kruskal Wallis Test where appropriate. Post-hoc analysis was conducted
using Bonferroni or Games-Howell test. p < 0.05 in relation to Neonate* and Infant!
Among 290 pediatric children, outcome data were available for 288. Out of 288 pediatric participants, 78%
recovered, 11% were referred, 7% died and 4% left against advice (Fig.1).
We compared the demographic, nutritional, comorbidity, and investigation proles between pediatric patients
with COVID-19 who died and those who recovered (Table4). The number of deaths was signicantly higher
among neonates than among infants and children (p < 0.05). Death did not vary signicantly with the sex,
nutritional status, or comorbidity of the patients. On investigation, hemoglobin, WBC count, neutrophil
percentage, serum creatinine, and serum potassium level were signicantly higher among those who died than
among those who recovered (p < 0.05). However, lymphocyte and monocyte percentages were signicantly
lower among patients who died than among those who recovered (p < 0.05).

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Table 4
Outcome of pediatric patients with COVID-19 in relation different characteristics (n = 290)
Variable Dead Recovered p-value
n (%) 20 (8.2) 224 (91.8) 
Age, n (%)   
Neonate 8 (19.5) 33 (80.5) 0.023*
Infant 5 (7.0) 66 (93.0) 
Children 7 (5.3) 125 (94.7) 
Sex, n (%)   
Male 12 (8.3) 132 (91.7) 0.926*
Female 8 (8.0) 92 (92.0) 
Nutritional Status, n (%)   
Normal 1 (2.0) 49 (98.0) 0.247*
Severe malnutrition 6 (9.7) 56 (90.3) 
Moderate malnutrition 1 (4.3) 22 (95.7) 
Overnutrition 0 1 (100.0) 
Number of comorbidities, n (%)   
One 7 (5.7) 115 (94.3) 0.176*
More than one 3 (16.7) 15 (83.3) 
None 10 (9.6) 94 (90.4) 
Investigation   
Hemoglobin (g/dl) 13.04 ± 4.02 10.93 ± 2.53 0.049***
Hematocrit (%) 41.43 ± 13.56 34.65 ± 8.81 0.059***
RBC (x 106/mm3)4.19 ± 0.92 4.18 ± 0.90 0.945***
WBC (x 103 /mm3)14.50 (1.10–37.10) 10.80 (0.01–127.80) 0.014
Neutrophil (%) 61.00 (41.00–89.00) 52.50 (3.00–89.00) 0.008
Lymphocyte (%) 30.00 (6.00–54.00) 41.00 (6.00–94.00) 0.012
Monocyte (%) 4.00 (0–11.00) 5.00 (1.00–25.00) 0.028
Eosinophil (%) 0 (0–6.00) 1.00 (0–16.00) 0.256
p
-
value determined by *Chi-square test, Fisher’s Exact test, ***Independent samples t test and Mann-
Whitney U test where appropriate

Page 10/16
Variable Dead Recovered p-value
Platelet (x 106/mm3)2.55 (0.24–5.78) 2.84 (0.12–7.76) 0.374
Serum creatinine (mg/dl) 0.70 (0.45–2.27) 0.47 (0.03–5.72) 0.011
Sodium (mmol/l) 142.47 ± 5.53 141.27 ± 5.58 0.402***
Potassium (mmol/l) 5.40 ± 0.90 4.41 ± 1.02 < 0.001***
Chloride (mmol/l) 104.44 ± 6.07 101.84 ± 13.52 0.436***
p
-
value determined by *Chi-square test, Fisher’s Exact test, ***Independent samples t test and Mann-
Whitney U test where appropriate
Discussion:
COVID-19 can affect any age. However, globally, the frequency and case fatality of COVID-19 is comparatively
low in the pediatric group[23]. Although several studies reported exclusively on children, a few studies
compared the demographic and clinical features across different age ranges[24, 25]. Our study presents a
comparative analysis of patient characteristics in neonates, infants, and children in the pediatric age group. We
also explored the factors affecting death among pediatric patients with COVID-19.
The median age of our participants was 18 months (1.5 years), and we obtained COVID-19-affected neonates
aged as low as one day and children as high as 17 years. Nearly half of the participants were aged less than
one year, which is higher than that found by Anwar
et al.
[26]. The median age of pediatric patients with COVID-
19 varies from study to study based on the target population and method of selection. A systematic review on
the pediatric group by Patel [24] found that the reported median age ranges from 1 to 11 years. The author also
presents a composite mean age of 7.9 years with an age range between 1 day and 17 years, similar to our
study. These ndings demonstrate the SARS-CoV-2 virus's ability to infect anyone and children most likely got
the virus from their infected parents or family members. This assumption is supported by studies among
neonates which showed that half of the patients had infections from their infected mother, and one-third were
admitted to the hospital [27].
Males were more common than females in our study, which corresponds to the ndings of other studies [24].
We found this true for all age range. The higher anity of SARS CoV-2 towards males than females might be
explained by the fact that angiotensin-converting enzyme 2 (ACE2), the receptor for the virus, is expressed more
in the former sex than in the latter along with other sex-based immunological and hormonal differences [28].
We found that more than 60 percent of pediatric patients had malnutrition irrespective of age group. This
nding is important, as nutrition shows a reciprocal relationship with infection, and good nutritional status is
associated with good immune function [29]. Additionally, more than half of them had at least one comorbidity,
with the frequency being signicantly higher among children and infants than among neonates. However, the
overall proportion of comorbidities found in our study was higher than that found in other studies [24] and
lower than that in those who needed neonatal intensive care unit admission[30]. Most of the comorbidities were
probably coincident or concomitant ndings in COVID-19 rather than precipitating factors. As the virus spreads
via airborne respiratory droplets and mostly causes mild or asymptomatic disease in the pediatric population,

Page 11/16
in most cases, it was a coincidental nding in children presenting with other diseases in the hospital. However,
some of the diseases might be consequent of COVID
-19 as well. We noted multisystem inammatory syndrome in 3 children, which was previously established as a
rare but severe complication of COVID-19 among children[31].
Fever was the most common presentation, followed by breathlessness, abdominal pain, cough, seizure, and
vomiting, among others. Two previous studies conducted among children with COVID-19 in Bangladesh[26, 32]
also noted fever, cough, breathlessness, abdominal pain, and vomiting among the most common presenting
features. In a systematic review of individual participant data, Christopher
et el
[33] reported similar patterns of
presentation. However, the proportion of individual symptoms varied among studies. SARS CoV-2 binds with
ACE2, which is ubiquitous in the human body with high expression in the lungs, heart, ileum, kidney, and
bladder[34]. Hence, despite its entry through the lung, it might produce symptoms involving multiple systems of
the body. However, respiratory and gastrointestinal intestinal intestinal presentation is the most common mode
of presentation of the disease. We found that neonates were relatively asymptomatic compared to infants and
children. Gastrointestinal complaints such as abdominal pain and vomiting were more common among
children, and respiratory complaints such as breathlessness and cough were more common among infants.
Christopher
et el
[33] noted that children less than 7 years old tended to present with gastrointestinal complaints
compared to older children. Our ndings also conform to their results, as most of the child participants in our
study were young with a median age of 64 months (5.33 years).
On laboratory investigations, we noted that children had signicantly lower WBC counts than neonates and
infants, with infants having signicantly lower neutrophils and higher lymphocyte counts than children.
However, laboratory data varied across pediatric participants based on the presence of various comorbidities
and were mostly within the normal range for the participants. Similarly, Patel noted that the test results
presented in various studies of COVID-19 children were mostly within the reference range used for that
particular study[24]. Interestingly, this is contrary to expected lymphopenia, and an elevated neutrophil-to-
lymphocyte ratio has emerged as a characteristic feature of severe COVID-19 [35], probably because of the
predominantly milder form of the disease in children.
Out of 288 participants for whom the outcome was known, 20 (6.9%) pediatric patients with COVID-19 died.
However, the case-fatality rate increased to 8.2% when referred patients were excluded. We found that age was
associated with death in pediatric patients with COVID-19, while sex, nutritional status, and the presence of
comorbidities did not show any association. The proportion of deaths was signicantly higher among neonates
than among infants and children. This rate is higher than that found by Ghosh et al[32] (1.4%) and Anwar et
al[26] (4.1%). The low number of neonates among their studies might explain the difference. However,
Trevisanuto
et al
[27] found zero case fatalities among 44 newborns with COVID-19. The provision of a well-
equipped and adequate number of neonatal intensive care units (NICUs) is an important requirement for the
appropriate management of these groups of patients. However, this is often not possible in developing
countries because of a lack of adequate treatment facilities. This could explain the high mortality among
neonates found in our study. Our analysis also revealed that certain investigation results were signicantly
different between dead and alive patients. However, this might have been inuenced by the higher number of
neonates dying instead of infants and children, as the physiology of neonates differs fundamentally from that
of older children.

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The current study was limited by the small sample size collected from a single center, lack of detection of
quantitative RT-PCR, radiological investigations, and dynamic detection of inammatory markers. However, our
study provided important insights into similarities and differences in characteristics, presentation, and outcome
of COVID-19 among neonates, infants, and children in the context of Bangladesh.
Conclusion
The study presents a detailed clinico-epidemiological pattern of COVID-19 among neonates, infants, and
children. About one-third of the patients remain asymptomatic. Fever and abdominal pain were the most
prominent manifestations among symptomatic patients. Slight variation in the symptoms and laboratory
investigations exists. In comparison to others, neonates are more vulnerable than other pediatric groups.
Declarations
Funding:None
Competing interest statement:The author declares no competing interest.
Consent to participate:Informed written consent was ensured before participation of all subjects from the
accompanying parents.
Availability of data and material:Data and material are available from the corresponding authors and could be
shared based on reasonable request.
Author contributions:
The conception and design: PKS, KG, MK, AM, MJH
Data acquisition and data collection: SA, MR, NA, NF, SAAA, MS, NN, SSA, SWR
Data analysis was done by AM, MJH, and KG
Interpretation of the result: PKS, KG, MK, AM, MJH, SA, MR, NA, NF, SAAA, MS, NN, SSA, SWR
Project administration: PKS, KG, SA, MR, NA, NF, SAAA, MS, NN, SSA, SWR
First draft of the manuscript: PKS, KG, MK, AM, MJH and NA
Review of the draft: PKS, KG, MK, AM, MJH, SA, MR, NA, NF, SAAA, MS, NN, SSA, SWR
Final approval: PKS, KG, and MJH
Acknowledgment:
The investigator team acknowledged the Department of Epidemiology & Research, Dhaka Shishu (Children)
Hospital for their constant support for data collection and data analysis, Child Health Research Foundation,

Page 13/16
Bangladesh for RT-PCR testing, and ‘Pi
Research Consultancy Center’ (www.pircc.org)
Bangladesh for their
cordial support for manuscript formatting and journal selection.
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Figures
Figure 1
Outcome of pediatric patients with COVID-19 (n=288)

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Supplementary Files
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1122.5.SupplementaryleV13.docx