key: cord-1020475-rp9zgfs2
authors: See, Kwee Ching; Tan, Li Peng; Ong, Li Teng; Lee, Pei Yin
title: Clinical and epidemiological characteristics of children with COVID-19 in Selangor, Malaysia
date: 2021-12-05
journal: IJID Regions
DOI: 10.1016/j.ijregi.2021.11.012
sha: 5b0f272a46faeaa5edf84e839933f800308bb4c1
doc_id: 1020475
cord_uid: rp9zgfs2

Objectives To describe the clinical and epidemiological characteristics of children diagnosed with coronavirus disease 2019 (COVID-19) at Hospital Sungai Buloh (HSgB), Selangor. Methods A retrospective, observational study was performed on children aged below 12 years diagnosed with COVID-19 infection between 25 January to 31 December 2020. Comparative analysis was undertaken between asymptomatic and symptomatic children, and a subanalysis on their caretakers’ COVID-19 status. Results A total of 1498 children were included – 48.7% Female, 51.3% male; mean age 5.6 years (Standard deviation (SD): 3.5 years). 82.3% were detected through contact tracing of positive family members or from the same household. 56.9% were asymptomatic. The most common symptoms reported were fever, nasal congestion/rhinorrhoea and cough. Symptomatic compared to asymptomatic children had higher reported comorbidities; low total white cell, absolute lymphocyte and absolute neutrophil counts; raised C-reactive protein and aspartate transaminase (p<0.05). Median duration of illness was 10 days (Interquartile range: 3 days). Overall outcome was good. Only 19 (8.2%) negative caretakers seroconverted prior to discharge. Conclusion Majority of the children in the state of Selangor experienced mild COVID-19 illness in 2020 and did not appear to be key drivers in the transmission of the disease.

The novel-Coronavirus disease 2019 has become an international health priority, since its first appearance in December 2019. Its infection rate and disease progress appear to differ significantly between adult and paediatric populations. Published data and clinical experience indicate that the paediatric population have milder symptoms, lower rate of infection, lower prevalence of disease and lower mortality rate (Centers for Disease Control and Prevention, 2021; Gaythorpe et al., 2021) .

Malaysia with a young population of 32.6 million people -with 10.5 million aged ≤19 years old (Department of Statistics Malaysia), experienced the COVID-19 outbreak in three waves in 2020 -January 25 to February 15, February 27 to July 8, and Oct 8 till beyond December 31 2020. (Hashim et al., 2021) . Our first reported cases involved two paediatric patients who were admitted to Hospital Sungai Buloh (HSgB) on 25 January 2020 (See et al., 2020) . As part of the Malaysian containment strategy, initially all patients suspected or confirmed for COVID-19 infection were admitted. By the third wave, only confirmed cases regardless of severity required mandatory admission to healthcare facilities. In Malaysia, children are still classified as a highrisk group for COVID-19. As such, national policy, e.g. school closure, and hospitalisation protocol are targeted to protecting this group (Ministry of Health Malaysia, 2020) .

Sungai Buloh Hospital, located in the northern region of Selangor, was the first hospital in the country designated as a COVID-19 health facility -extending from its original role as the National Infectious Disease centre. Selangor is the most populous state in Malaysia with 6.53 million residents over 7,951km 2 . It encloses two federal territories -the Federal Territory of

Case was defined as a child confirmed with COVID-19 infection via reverse-transcriptasepolymerase chain reaction (RT-PCR) analysis or rapid test kit antigen (RTK-Ag) of nasopharyngeal and/or oropharyngeal swabs at designated National Public Health laboratories, Institute of Medical Research or accredited hospital laboratories. Viral detection using RTK-Ag without confirmatory RT-PCR was accepted in selected situations where there was strong epidemiology link and reduced laboratory capacity at the time due to caseload surge. Strong epidemiological link was taken as having multiple family or community members diagnosed with COVID-19 during the same period.

Date of onset (of illness) was defined as the date of earliest symptoms -up to two months before admission till up to discharge (Han et al., 2021) . If this date was unavailable, then the date of positive swab was taken as the date of onset. Duration of illness was calculated from date of onset to date of discharge. Standard duration of quarantine (thus admission) varied according to changes in national policy-but were between 10 to 14 days from positive detection.

All symptoms, including those possibly due to underlying comorbidities, or unrelated to COVID-19, or due to co-infection were reported. Illness severity was staged according to Ministry of Health guidelines (Ministry of Health Malaysia, 2020) -Category 1 (Cat 1): asymptomatic, Category 2 (Cat 2): symptomatic without pneumonia, Category 3 (Cat 3): symptomatic with pneumonia, without requiring supplemental oxygen, Category 4 (Cat 4): symptomatic with pneumonia, requiring supplemental oxygen and Category 5 (Cat 5): critically ill with multi-organ involvement. Illness severity was assigned based on worst symptoms experienced throughout illness, including before or during admission. Two children were restaged from Cat 2 to Cat 3, following retrospective analysis of radiographic images.

Only one caretaker was assigned per person, even though a child may have been accompanied by two or more caretakers. The caretaker of choice, for data collection, was the one positive for COVID-19.

Variables with missing data are reported in Supplementary Table S1 & S2. Missing data were omitted from statistical analysis. Continuous variables were described using mean and standard deviation if normally distributed and using median and interquartile range (IQR) if not normally distributed. Categorical variables were described using frequency (n) and percentage (%).

Results of blood investigations were categorised into normal, abnormally high or abnormally low, using reference values by age (See Supplementary Table S3 ). Statistical tests such as independent t-test, Mann Whitney U test and Chi-square test were performed to assess differences between asymptomatic (Category 1) and symptomatic (Category 2-5) children; and a targeted analysis comparing caretaker status with their children's epidemiology link, using IBM SPSS Stastistics Version 26.

The study was registered with the National Medical Research Register and approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia.

Baseline characteristics 3 A total of 1498 children below 12 years old were admitted to Hospital Sungai Buloh with median 4 age of 5.4 years (IQR: 2.5-8.5 years) and male-to-female ratio of 1.05 [ Table 1 ]. About 14.8% of children had comorbidities with bronchial asthma (2.9%), allergies (2.6%) and eczema (2%) 6 being the top three most frequently reported. The vast majority of children (96%) had completed 7 their routine vaccination up to age. About 56.9% of children were asymptomatic (Cat 1) during their entire illness. A further 41.5% 22 were symptomatic, but had no pneumonia (Cat 2). Only 11 (0.5%) patients were diagnosed with 23 COVID-19 pneumoniathree (0.5%) not requiring oxygen support (Cat 3) and four (0.3%) who 24 did (Cat 4). Frequency of symptoms in order from highest to lowest is shown in Table 3 . The 25 most common symptoms were: fever, nasal congestion / rhinorrhoea and cough.

Overall, investigations were normal in the majority of children, even amongst symptomatic patients. However, symptomatic children had higher incidence of low TWC (8.0% vs 3.6%, p<0.025), low ALC (7.0% vs 1.0%, p<0.001) and low ANC (19.4% vs 8.6%, p<0.001). High CRP was more frequent in symptomatic patients (12.5% vs 1.2%, p<0.001) [ Table 2 ].

Routine liver enzymes (AST & ALT) investigation showed normal liver enzyme function in 634 children (88.7% out of 715 children with both tests done). There was a higher incidence of raised AST amongst symptomatic children (8.1% vs 3%, p=0.004). But no children from Cat 4 had abnormal liver enzymes and only one child from Cat 3 [ Table 4 ].

Only 26 children had chest radiography performed (See Table 5 for findings breakdown based on illness severity). All asymptomatic children had normal x-rays. Three children had x-rays reported abnormal with changes probably due to COVID-19. Ten children had abnormal x-rays with changes not specifically attributed to COVID-19.

The majority of children recovered from their illness without any treatment. Only 10.4% required treatment -of this 83.9% were given symptomatic treatment (e.g. oral rehydration salts, nasal saline drops, metered dose salbutamol inhaler), 16.8% were given antibiotics to cover for bacterial infection and only one child (0.6%) was given antiviral for only 1 day. The remainder of treatment consisted of pre-existing medications, treatment for fungal rashes, etc. The median duration of illness was 10 days (IQR 3 days).

No children required ICU admission and all children were discharged alive and well from the hospital. Children who were newly diagnosed with any comorbidities during admission, e.g. obesity, bronchial asthma, were given referred back for follow up at their respective local healthcare facilities. Only 8 children had recurrent visits to HSgB for COVID-19 related issues.

For one child, the admission to HSgB was the second admission during his illness. Five children presented to the ED with mild symptoms and were discharged with treatment and extension of home quarantine. Range of duration to recurrent presentation for symptomatic patients (n=6) : 2-78 days. Two children were seen at the HSgB Paediatric Specialist clinic to follow up on biochemical abnormalities but were otherwise, clinically well.

There were more children with comorbidities in the symptomatic group (19.1% vs 12.9%, p=0.001). Particularly of those with self-reported allergies (3.9% vs 1.9%, p=0.022), eczema (3.1% vs 1.4%, p=0.028) or gastrointestinal pathology (1% vs 0, p = 0.005).

Children were most frequently cared for by their parent (90.0%) and only 11 children (0.7%) had no caretaker in the ward [ Table 1 ]. There were a total of 1101 caretakers for the 1498 children.

Majority of caretakers (819 people, 77.9%) tested positive for COVID-19 on admission [ Table   7 ].

As mentioned earlier, children were most frequently detected through case screening within a family cluster. Concurrent household contact was present in 97.6% of this group of children. In contrast, only 28% of children with school/child-care-linked epidemiology had concurrent household contacts (p<0.001) [ Table 6 ]. Children identified from school/childcare contact were more likely to be accompanied by a negative carer (78.6% vs 15.3% , p<0.001) and none of these negative carers seroconverted (p<0.001) [ Table 7 ].

Two main factors contributed to missing data in our study. These were different record handling when patient volume surged and non-standardised clerking. With regards to investigations, standard blood investigations (full blood count (FBC), liver function tests (LFT) +/-renal profile (RP), C-reactive protein (CRP) were sent for all positive patients until 1 December 2020.

Subsequently, blood investigations were only performed on a case-to-case basis, depending on the attending clinician's discretion. Chest x-rays were not performed routinely from the start of the pandemic.

Our data is consistent with international reports of the reduced severity of COVID-19 in children (Alsharrah et al., 2020; Arslan et al., 2021; Hoang et al., 2020; Ng et al., 2021; Parcha et al., 2021; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Xu et al., 2020) , with the overwhelming proportion only being detected through contact tracing, predominantly of a family contact. The most common symptoms, when manifested, were fever, nasal congestion/rhinorrhoea and cough. Similar to observations reported by the International Paediatric Association (Klein et al., 2020) , children less than 1 years old and with comorbidities were more likely to be symptomatic. The prevalence of comorbidities in our study population was 15% compared to 25 % in adults (Sim et al., 2020) . Atopic disease was the most common reported comorbidities. The presence of symptoms or comorbidities did not affect overall outcome. Most children did not require any treatment during the course of their illness, none required ICU admission, all recovered fully prior to discharge and only a handful were seen at Hospital Sungai Buloh after 6 months.

There were some significant differences in laboratory values between asymptomatic and symptomatic children. For instance, low total white cell count (TWC), low absolute lymphocyte count (ALC), low absolute neutrophil count (ANC) and raised aspartate transaminase (AST).

However, as all the children fully recovered with minimal intervention, we maintain routine blood sampling is not recommended.

By the low number of recurrent visits to our hospital post-discharge, we presume that there were no serious complications e.g. multisystem inflammatory syndrome in children (MIS-C) amongst this study population. Although this needs confirmation with data from surrounding healthcare facilities where children may have been seen without referrals to ourselves.

Children, with their developing immune systems, have more frequent respiratory infections compared to adults. Toddlers and school children have on average 8 respiratory infections a year, compared to 2-3 in adults (Thomas, 2021) . There is an on-going concern on the infectivity of children and their potential as the asymptomatic reservoir for the transmission of SARS-COV-2 virus (CodeBlue, 2021; Han et al., 2021; Lu et al., 2020) .

The current study supports the hypothesis that children may not be a potent source of COVID-19 infection, although there are obvious limitations in the localised nature of our population and lack of detailed analysis of related factors. Only 50 children were detected through school/childcare contact, albeit school/childcare were closed for a significant portion of the year in Malaysia (Buonsenso et al., 2021) . These children were more likely to be accompanied by a negative caretaker. Furthermore, only about 8% of all negative caretakers seroconverted after accompanying their positive child during their admission. Ng et.al. (2021) showed that despite a rise in cases coinciding with school reopening, this rise was simultaneously preceded by an increase in adult cases. This suggests a general reopening of community activities as contributing to the rise in cases, rather than school per se. In Sweden (Ludvigsson et al., 2020) and Norway (Brandal et al., 2021) where schools were allowed to stay open during their outbreaks, there was minimal child-to-child and child-to-adult transmission of COVID-19.

School closure is a containment strategy to target child-to-child and child-to-adult transmission.

However, the evidence suggests that transmission through school or childcare is not the main driver for this disease.

Children have been largely spared from direct COVID-19 infection. But children may suffer its long-term consequences through its impact on driving their families into poverty, interruption in learning, overall effect on safety and health, through reduction in income, social and health services (United Nations, 2020).

As with any childhood illness, family and community involvement is crucial to their recovery.

We had 1101 carers admitted together with 1498 children. Granted the majority of them were admitted in their own right, at least 20% of them (negative caretakers) were admitted solely as caretakers. The pandemic has resulted in double-income households becoming single-income households, or single-to nil-income households. This effect extends beyond a child's admission to hospital, due to school/childcare services closure.

Article 28 of the United Nations Convention on the Rights of the Child (1989) upholds a child's right to education. In recognition of this right, primary schooling is mandatory in Malaysia (Education Act, 1996) . Schools provide the environment for both formal and informal education; provide safeguarding and supervision to enable their working parents to earn a living; and in some communities, are a main source access to nutritous food, safe water and healthcare services (Armitage & Nellums, 2020) . Strategies undertaken to mitigate the loss of school hours, such as online learning, may serve to replace formal education but are inadequate to address the loss of other equally important school functions. While school closure has been one of the methods employed to reduce the spread of COVID-19, a continuing review with scientific evidence of the benefits and harm is necessary.

The COVID-19 disease was mild in children of Selangor in the year 2020. However, even as this report is being finalised, variants of concern ravage our communities with children being increasingly affected. Therefore, we remain cautious on the applicability of our findings going forward and urge our fellow practitioners to be vigilant on the acute disease and possible complications in previously asymptomatic children (e.g. MIS-C).

The health of our children is not the only parameter by which we should analyse the impact of COVID-19. Overall child welfare includes consideration of missed schooling, socialising and learning opportunities, missed routine vaccination, psychological impact, and alteration of family dynamics. One of our study's limitations was its inability to analyse the impact of these pyschosocio-economic factors and warrants future further investigation.

Nonetheless, we believe our findings will contribute to the global pool of knowledge. Our understanding of COVID-19 in children and adult must grow in tandem so that we may better combat this disease and its ill effects on our health and lives.

Nations. ---* 4 children (3 Cat 2, 1 Cat 1) no AST taken -ALT normal ** 1 child (Cat 2) no ALT taken -AST high; 1 child (Cat 2) no ALT taken -AST normal 

Clinical characteristics of pediatric SARS-CoV-2 infection and coronavirus disease

Considering inequalities in the school closure response to COVID

Clinical Characteristics of Pediatric COVID-19 and Predictors of PCR Positivity

Paediatric activities and adherence to vaccinations during the COVID-19 epidemic period in Tuscany, Italy: a survey of paediatricians

Schools Closures During the COVID-19 Pandemic

Minimal transmission of SARS-CoV-2 from paediatric COVID-19 cases in primary schools

GitHub-MoH-Malaysia/covid19-public: Official data on the COVID-19 epidemic in

Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea

COVID-19 Epidemic in Malaysia: Epidemic Progression, Challenges and Response

COVID-19 in 7780 pediatric patients: A systematic review

Promoting and supporting children's health and healthcare during COVID-19 -International Paediatric Association Position Statement

Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden

Clinical and epidemiological characteristics of children with COVID-19 in Negeri Sembilan

A retrospective cohort study of 12,306 pediatric COVID-19 patients in the United States

Royal College of Paediatrics and Child Health

Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration -United States

COVID-19: Four Paediatric Cases in Malaysia

Clinical characteristics and risk factors for severe COVID-19 infections in Malaysia: A nationwide observational study. The Lancet Regional Health -Western Pacific

The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital Surveillances: The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) -China

Upper Respiratory Tract Infection -StatPearls -NCBI Bookshelf

We would like to thank the Director General of Health Malaysia for his permission to publish this manuscript. In addition, sincerest thanks to the Hospital Sungai Buloh Paediatric team, Dr