ABSTRACT
Background and Aims
There is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID‐19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID‐19 in Iran.
Methods
A retrospective study was performed to assess medical records of children with COVID‐19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded.
Results
In this study, 600 medical records of pediatric COVID‐19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID‐19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID‐19 had substantially higher levels of various inflammatory markers (C‐reactive protein (CRP), fibrinogen, and d‐dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma‐glutamyl transferase (GGT) compared to children with mild COVID‐19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID‐19 (p < 0.001). In addition, children with severe or moderate COVID‐19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID‐19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID‐19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate‐to‐severe COVID‐19 compared to patients with mild COVID‐19 (p < 0.001).
Conclusion
The outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID‐19 compared to those with mild COVID‐19.
Keywords: children, clinical features, COVID‐19, epidemiology, malnutrition, pediatric
1. Introduction
Coronavirus disease 2019 (COVID‐19) is a highly pathogenic, contagious, and easily transmissible infection [1]. The outbreak of COVID‐19 has created a global public health challenge and an emerging threat [2]. The majority of children with COVID‐19 experienced less severe COVID‐19 disease progression and had better outcomes than adults [3, 4]. The global prevalence of pediatric deaths and severe cases was approximately 0.3% and 0.6%–5%, respectively [5]. At the population level, children comprise a small percentage of COVID‐19 infections, and they are typically acquired through adult contact [6, 7].
The severity and prevalence of COVID‐19, along with its diverse spectrum of symptoms, are lower in children compared to adults [8]. The lower expression of the angiotensin‐converting enzyme‐2 (ACE‐2) receptor, the reactive immune system, and the balance between immune tolerance and inflammatory response are some theories that explain these characteristics in children [9]. It was reported that COVID‐19 was more prevalent among boys [10]. Cough, fever, sore throat, diarrhea, dyspnea, and vomiting were the most frequent symptoms in children with COVID‐19 [10]. In pediatric patients with COVID‐19, the most common laboratory findings were elevated d‐dimer and decreased oxygen saturation levels [10]. The severe course of COVID‐19 in children revealed a range of symptoms, such as prolonged fever, cardiac dysfunction, abdominal pain, and shock to the multisystem inflammatory syndrome in children (MIS‐C) [11, 12]. Patients with comorbidities have a greater risk of severe COVID‐19 and its related mortality than those without underlying disease; the most common comorbidities that increase the risk are neurological conditions, cardiac disease, and obesity [13, 14]. The potential role of nutrition has been highlighted in the progression and vulnerability to COVID‐19 [15].
The majority of pediatric patients with COVID‐19 are asymptomatic or presymptomatic, which highlights the importance of ongoing monitoring to track the spread of this disease in the pediatric population and improve prompt laboratory identification for clinical management [16]. A limited number of studies have been performed among children with COVID‐19 in Iran [17, 18, 19, 20, 21, 22, 23]. However, all aspects of COVID‐19 in children were not thoroughly investigated. Therefore, this study aimed to identify clinical and epidemiological characteristics of pediatric COVID‐19 in Iran.
2. Material and Methods
The current retrospective study evaluated the medical records of 657 pediatric patients with COVID‐19 (aged 1–16 years) admitted to Abuzar Hospital in Ahvaz (Iran), from May 2022 to May 2023. The real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) method [24] was employed to establish a definitive diagnosis of COVID‐19. The extent of pulmonary involvement in patients with moderate‐to‐severe COVID‐19 was evaluated using computed tomography (CT) imaging. The study excluded patients with incomplete or inaccurate medical information, as well as those without RT‐PCR confirmation of COVID‐19. Ultimately, the medical records of 600 children and adolescents were analyzed after excluding 57 patients based on predetermined criteria. Written consent from the parents or guardians of the children was not obtained, as the research did not involve any patient‐identifiable information and utilized a retrospective design.
COVID‐19 infection severity was classified into three categories: severe, moderate, and mild, based on clinical symptoms, chest radiography results, and laboratory tests [25]. Mild cases of COVID‐19 were identified by normal respiratory function tests and symptoms resembling upper respiratory tract infection (URTI), including nasal congestion, sore throat, fatigue, cough, myalgia, and fever [26]. Moderate cases of COVID‐19 were characterized by pneumonia with fever or cough, radiographic evidence of COVID‐19 on chest CT scan CT, and the absence of dyspnea and hypoxemia [26]. Severe cases of COVID‐19 in children were defined by symptoms such as fever, cough, dyspnea, and central cyanosis (arterial oxygen saturation below 92%) [26].
The extracted data included clinical, laboratory, and demographic information, length of hospital stay (LOS), nutritional status (assessed through standard Z‐scores), presence of comorbidities, and discharge conditions. Children with serum vitamin D levels of more than 20 ng/mL, less than 12 ng/mL, and between 12 and 20 ng/mL had normal levels of vitamin D, deficiency, and insufficiency, respectively [27].
Anemia in children was classified based on the criteria set by the World Health Organization (WHO) that defined anemia as a hemoglobin level below 11.0 g/dL for children aged 6–59 months, below 11.5 g/dL for children aged 5–11 years, and below 12.0 g/dL for children aged 12–14 [28]. The evaluation of nutritional status in children using a single anthropometric measurement, such as weight‐for‐age z‐score (WAZ), is employed when only one data point is available for assessment [29, 30]. Malnutrition was categorized into three classifications based on WAZ. Mild, moderate, and severe malnutrition were defined according to specific z‐score thresholds: < −1, < −2, and < −3, respectively [29, 30, 31].
2.1. Statistical Analysis
The study utilized the SPSS statistical software (version 25) for data analysis. The normal distribution of data was evaluated applying the Kolmogorov–Smirnov test. Descriptive statistics such as mean, percentage, and standard deviation (SD) were employed to examine the data. The analysis of the data was conducted using the independent‐sample t‐test, Chi‐square (χ 2), and ANOVA (analysis of variance) tests. A two‐tailed p‐value lower than 0.05 was used to determine statistically significant outcomes.
3. Results
This study included 600 medical records of children with COVID‐19. Clinical and demographic characteristics of the patients categorized by disease severity of COVID‐19 are summarized in Table 1. More than 50% of the children were boys between the ages of 1 and 5 years. Significant gender and age differences were found between the three groups of patients who were categorized based on COVID‐19 disease severity (Table 1). The average age of the children was 71 months (range: 1–16 years). Mild, moderate, and severe COVID‐19 were identified in 250, 200, and 150 children, respectively. Seventy‐five patients (12.5%) had an underlying disease (diabetes and pulmonary diseases), and the majority of them had severe to moderate COVID‐19. The most prevalent symptoms were dry cough and fever. In addition, 50.6% and 31.5% of patients had malnutrition and anemia, respectively. The prevalence of anemia in children with mild, moderate, and severe courses of COVID‐19 was 10%, 31%, and 68%, respectively (Table 1). Seventy‐six children (50.7%) with severe COVID‐19 were admitted to the pediatric intensive care unit (PICU) and a mortality rate of 3.3% was recorded. Malnutrition was observed among all patients in the PICU. The prevalence of malnutrition was higher in children under the age of five compared to children in other age groups. Moreover, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate to severe COVID‐19 compared to those with mild COVID‐19. The incidence of vitamin D insufficiency or deficiency in patients with moderate, mild, and severe courses of COVID‐19 was 34.1%, 8.6%, and 57.3%, respectively (Table 1).
Table 1.
Clinical and demographic characteristics of COVID‐19 patients categorized by disease severity (n = 600).
| Parameters | Mild (n = 250) | Moderate (n = 200) | Severe (n = 150) | p‐Value | |
|---|---|---|---|---|---|
| n (%) | |||||
| Age | 1–5 years | 98 (39.2) | 187 (93.5) | 20 (13.3) | < 0.001 |
| 5–10 years | 98 (39.2) | 6 (3) | 104 (69.3) | ||
| > 10 | 54 (21.6) | 7 (3.5) | 26 (17.3) | ||
| Gender | Male | 164 (65.6) | 109 (46.6) | 74 (49.3) | < 0.01 |
| Female | 86 (34.4) | 91 (45.5) | 76 (50.7) | ||
| Fever > 38°C | 20 (8) | 92 (46) | 127 (84.7) | < 0.001 | |
| Dry cough | 32 (12.8) | 76 (38) | 127 (84.7) | < 0.001 | |
| Nutritional status (weight/age) | Malnourished | 17 (7) | 159 (79.5) | 128 (85) | < 0.001 |
| Anemia | 25 (10) | 62 (31) | 102 (68) | < 0.001 | |
| Vitamin D deficiency or insufficiency | 22 (8.6) | 87 (34.1) | 146 (57.3) | < 0.001 | |
| Comorbidities | 5 (2) | 20 (10) | 50 (33.3) | < 0.001 | |
| PICU ward | 0 | 0 | 76 (50.7) | < 0.001 | |
| Mean ± SD | |||||
| Age (months) | 81 ± 4 | 39 ± 2 | 96 ± 3 | < 0.001 | |
| Length of hospital stay (days) | 0 | 6 ± 2 | 10 ± 4 | < 0.001 | |
| Serum vitamin D (ng/ml) | 30 ± 13 | 25 ± 12 | 14 ± 4 | < 0.001 | |
| ALT (U/L) | 20.4 ± 0.5 | 23 ± 0.7 | 29.5 ± 0.4 | < 0.001 | |
| GGT (U/L) | 20.6 ± 0.2 | 25 ± 0.1 | 32.5 ± 0.7 | < 0.001 | |
| AST (U/L) | 17.5 ± 0.4 | 21.2 ± 0.2 | 25 ± 0.3 | < 0.001 | |
| LDH(U/L) | 164 ± 0.3 | 195.5 ± 0.4 | 282 ± 0.2 | < 0.001 | |
| CPK (μg/L) | 60.4 ± 0.5 | 80.4 ± 0.3 | 108.5 ± 0.4 | < 0.001 | |
| BUN (mmol/L) | 4.2 ± 0.1 | 6.1 ± 0.2 | 7.2 ± 0.1 | < 0.001 | |
| Hb (g/dL) | 12.1 ± 1.4 | 11.8 ± 1.3 | 11.2 ± 1.1 | < 0.001 | |
| Cr (μmol/L) | 22.1 ± 0.1 | 24.2 ± 2 | 32.1 ± 0.2 | < 0.001 | |
| Fibrinogen (mg/dL) | 237 ± 35 | 311 ± 21 | 352 ± 25 | < 0.001 | |
| Bilirubin (µmol/L) | 6.1 ± 1 | 9.1 ± 0.1 | 12.4 ± 2.4 | < 0.001 | |
| Lymphocyte count (103 μL) | 2.5 ± 0.4 | 2.1 ± 0.3 | 1.7 ± 0.2 | < 0.001 | |
| d‐dimer (mg/L) | 0.4 ± 0.1 | 0.8 ± 0.1 | 1.3 ± 0.1 | < 0.001 | |
| Neutrophil count (103 μL) | 2.5 ± 0.3 | 3.2 ± 0.4 | 3.5 ± 0.7 | < 0.001 | |
| CRP (mg/L) | 17.3 ± 4.2 | 24 ± 2.6 | 29 ± 3.2 | < 0.001 | |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; COVID‐19, coronavirus disease 2019; CPK, creatine kinase; CR, creatinine; CRP, C‐reactive protein; GGT, gamma glutamyl‐transferase; Hb, hemoglobin; LDH, lactate dehydrogenase; PICU, pediatric intensive care unit; SD, standard deviation.
Children with moderate or severe courses of COVID‐19 had substantially higher levels of inflammatory markers (fibrinogen, C‐reactive protein (CRP), and d‐dimer), gamma‐glutamyl transferase (GGT), alanine transaminase (ALT), creatinine (Cr), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), neutrophils, creatine kinase (CPK), aspartate aminotransferase (AST), and bilirubin compared to children with mild COVID‐19 (p < 0.001); they had lower values of lymphocytes, hemoglobin (Hb), and vitamin D than the mild COVID‐19 cases (p < 0.05). Furthermore, they had a considerably higher prevalence of dry cough or fever and longer hospital stays than those with mild COVID‐19 (p < 0.001). Moreover, 17.6% (n = 106) and 33% (n = 198) of patients were moderately and mildly underweight, respectively. In addition, 87 (14.5%) and 118 (19.6%) patients were moderately and mildly stunted, respectively. The majority of underweight and stunted children had moderate and severe courses of COVID‐19. Table 2 displays the anthropometric characteristics of the children based on the severity of COVID‐19 and gender.
Table 2.
Anthropometric assessment of COVID‐19 patients categorized by disease severity and gender (n = 600).
| Anthropometric profile | Severity of COVID‐19 | |||||
|---|---|---|---|---|---|---|
| Mild (n = 250) | Moderate (n = 200) | Severe (n = 150) | ||||
| Boys (n = 164) | Girls (n = 86) | Boys (n = 109) | Girls (n = 91) | Boys (n = 74) | Girls (n = 76) | |
| Mean ± SD | Mean ± SD | Mean ± SD | ||||
| Weight (kg) | 24 ± 12 | 22 ± 9 | 13 ± 4 | 15 ± 7 | 23 ± 9 | 30 ± 7 |
| Height (cm) | 116 ± 25 | 112 ± 27 | 88 ± 14 | 99 ± 18 | 115 ± 23 | 135 ± 10 |
| Weigh‐for‐age Z‐Score | n (%) | n (%) | n (%) | |||
| Moderate underweight (–3 to −2.01 WAZ) | 9 (5.5) | ‐ | 25 (23) | 2 (2) | 40 (54) | 30 (39.5) |
| Mild underweight (−2 to ‐1.01 WAZ) | 1 (0.6) | 7 (8.1) | 64 (59) | 68 (75) | 22 (30) | 36 (47.4) |
| Normal (±1.00 WAZ) | 154 (93.9) | 79 (91.9) | 20 (18) | 21 (23) | 12 (16) | 10 (13.1) |
| Height for age Z‐score | ||||||
| Moderate stunting (–3 to −2.01 HAZ) | 9 (5.5) | 6 (7) | 28 (25.7) | 20 (22) | 21(28.4) | 3 (4) |
| Mild stunting (−2 to ‐1.01 HAZ) | 46 (28) | 3 (3.5) | 20 (18.3) | 21(23) | 15 (20.3) | 13 (17) |
| Normal (±1.00 HAZ) | 109 (66.5) | 77 (89.5) | 61 (56) | 50 (55) | 38 (51.3) | 60 (79) |
4. Discussions
This study identified 250, 200, and 150 pediatric patients with mild, moderate, and severe COVID‐19, respectively. It was indicated that children with severe or moderate manifestations of COVID‐19 had substantially elevated levels of various inflammatory markers (fibrinogen, d‐dimer, and CRP), neutrophils, ALT, BUN, CPK, AST, LDH, Cr, GGT, and bilirubin in comparison to those with mild COVID‐19. Conversely, they had decreased levels of lymphocytes, Hb, and vitamin D compared to patients with mild COVID‐19. Furthermore, children with severe or moderate COVID‐19 had a higher incidence of dry cough or fever and longer hospital stays than those with mild COVID‐19. These observations align with prior studies [32, 33, 34]. It was reported that the level of d‐dimer was considerably increased in patients with severe COVID‐19 [35]. A study revealed that over a third of COVID‐19 patients displayed abnormal liver function [36]. Changes in the concentrations of serum biomarkers were also observed in COVID‐19 patients [37]. A potential biomarker for disease severity is CRP, which had abnormal values in pediatric patients with COVID‐19 [37]. Another study identified that the fibrinogen level upon admission served as a prognostic indicator for severe COVID‐19 [17]. In addition, it was stated that AST, LDH, BUN, and ALT could independently predict the progression from mild to severe COVID‐19 [35].
In the current study, the prevalence of insufficient or deficient levels of vitamin D in children with moderate, mild, and severe manifestations of COVID‐19 was 34.1%, 8.6%, and 57.3%, respectively. It was suggested that the deficiency of vitamin D may contribute to hyperinflammation and decreased lymphocyte levels in COVID‐19 cases [38]. In addition, significant reductions in lymphocyte counts have been observed in patients with severe COVID‐19 [39, 40, 41]. These findings are consistent with the outcomes documented in this study and other research conducted among pediatric COVID‐19 patients in Iran [17] and Turkey [38]. A cohort study has identified a correlation between vitamin D deficiency and elevated susceptibility to COVID‐19 [42]. Furthermore, patients with sufficient levels of vitamin D had notably reduced LOS in hospital and decreased levels of inflammatory markers [42], findings that align with the findings of the current study.
An increased likelihood of mortality and severe COVID‐19 among patients with COVID‐19 may be linked to elevated CRP levels, which are associated with vitamin D deficiency [42, 43]. In this study, 50.7% of children with severe COVID‐19 (12.6% of the total cases) were admitted to the PICU and a mortality rate of 3.3% was recorded. Malnutrition was detected in all COVID‐19 patients in the PICU. The presence of malnutrition upon hospital admission has been correlated with an increased probability of ICU admission and higher mortality rates in COVID‐19 patients [44]. In addition, it has been associated with adverse outcomes in patients hospitalized with COVID‐19 [45]. A significant inverse relationship has been reported between the mortality rate and the levels of vitamin D in patients with COVID‐19 [46]. A meta‐analysis and systematic review revealed that children with vitamin D deficiency were at higher risk of COVID‐19 and experienced worse outcomes compared to patients with sufficient vitamin D levels [47].
In this study, more than 50% of the children were boys between the ages of 1 and 5 years, which was consistent with previous studies [5, 48, 49]. There was a significant gender difference. Seventy‐five patients (12.5%) had an underlying disease (diabetes and pulmonary diseases) and the majority of them experienced moderate or severe cases of COVID‐19. A similar trend was noted in a study conducted among 1019 pediatric COVID‐19 cases in Thailand, where a significantly higher proportion of severely or critically ill patients had an underlying health condition [5]. Patients with lower respiratory tract infections (LRTIs) experienced a more severe form of COVID‐19 [5].
In the present study, 17.6% of the patients were moderately underweight, while 33% were mildly underweight. In addition, 50.6% and 31.5% of children had malnutrition and anemia, respectively. Furthermore, 14.5% and 19.6% of patients were moderately and mildly stunted, respectively. The majority of underweight and stunted children had moderate and severe COVID‐19. The incidence of malnutrition was higher among children under the age of five compared to children in other age groups. It was reported that children aged between 6 and 17 years with a history of malnutrition had a higher risk of COVID‐19 [50]. In this study, the incidence of anemia in children with mild, moderate, and severe COVID‐19 was 10%, 31%, and 68%, respectively. There was a considerably higher prevalence of malnutrition, anemia, vitamin D insufficiency, or deficiency in children with severe to moderate COVID‐19 than those with mild COVID‐19. It was reported that anemia is related to an elevated risk of severe COVID‐19 [51, 52]. In addition, the progression to severe COVID‐19 was independently associated with anemia (based on hemoglobin status) [53, 54]. The nutritional status of individuals may play a critical role in immune function and significantly influence their susceptibility to the risk of COVID‐19 [15].
The current study was one of a limited number of studies conducted among children with COVID‐19 in Iran. The findings have the potential to improve perceptions of the clinical and epidemiological status of pediatric patients with COVID‐19 in a Middle Eastern country with a middle‐income status. The study had some limitations, such as having a retrospective design. In addition, it was performed in a single‐center setting. The medical records of children may probably be incomplete or incorrect. It was not possible to assess some of the clinical parameters. However, it may provide a better insight for further studies on pediatric COVID‐19. This study may be relevant to other research on COVID‐19 [17, 18], LRTIs [55, 56], and PICU [57] among pediatric patients in the same hospital.
5. Conclusions
This study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated levels of liver and kidney function tests, and increased inflammatory markers in children with moderate to severe COVID‐19 compared to those with mild symptoms. Further studies are required to comprehensively assess all clinical aspects of COVID‐19 in children.
Author Contributions
Mohammadreza Mirkarimi: conceptualization, data curation, investigation, methodology, project administration, resources, supervision, writing–review and editing. Solmaz Heidari: data curation, methodology, project administration, supervision, writing–review and editing, resources. Ahmad Shamsizadeh: project administration, writing–review and editing, supervision. Kia Tahouri: data curation, investigation, writing–review and editing. Mohsen Alisamir: conceptualization, data curation, writing–review and editing, project administration, supervision, investigation, methodology, resources. Mohammadreza Fathi: writing–review and editing, supervision, project administration. Shooka Mohammadi: writing–review and editing, writing–original draft, formal analysis, data curation.
Ethics Statement
The medical ethics committee of Ahvaz Jundishapur University of Medical Sciences (AJUMS) approved the protocol of the study (IR.AJUMS.REC.1399.821).
Conflicts of Interest
The authors declare no conflicts of interest.
Transparency Statement
The lead author Mohsen Alisamir affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as plannedhave been explained.
Standard of Reporting
The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist has been followed in this study.
Acknowledgments
This study did not receive any specific grant from any funding agency.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.