Coronavirus Disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020 (1) and led to approximately 7 million confirmed deaths in both pediatric and adult populations (2). The clinical presentation of COVID-19 varies, ranging from asymptomatic cases to those involving multiple organs (3). Compared to adults, children generally experience a lower incidence, milder symptoms, and reduced mortality rate (3–9). Common symptoms in children include fever and cough, with additional manifestations such as shortness of breath, sore throat, headache, dizziness, myalgia, and gastrointestinal symptoms (6, 10, 11).

Some pediatric patients, especially infants and toddlers, may require hospitalization and face a higher risk of complications and mortality (7, 10). Certain underlying medical conditions are associated with more severe symptoms and outcomes (12). Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are vulnerable to severe complications, including acute respiratory distress syndrome, myocarditis, acute renal and multi-organ failure, and multisystem inflammatory syndrome in children (MIS-C) (13). MIS-C represents a hyperinflammatory state linked to SARS-CoV-2 infection, posing a significant risk of morbidity and mortality (6). It's noteworthy, however, that the overall mortality rate among children remains relatively low, as indicated by a meta-analysis reporting a rate of 2.4 percent (13, 14).

In Iran, over 140,000 deaths related to COVID-19 have been reported in general population (11). However, the actual number of COVID-19 cases is likely higher (15). Numerous studies have described the clinical characteristics of children with COVID-19 in Iran since the outbreak began (7, 16–23). In a comprehensive report covering 18 months of the epidemic and 20,506 admitted patients, intensive care unit (ICU) admission, ventilator use, and total mortality rates were reported at 14.5%, 5.7%, and 2.9% of the cases, respectively (7). Another multicenter study involving 645 patients reported a mortality rate of 2.5%, primarily among individuals with comorbidities and dyspnea (18).

The vaccination rates for COVID-19 are remarkably lower in children, with many countries refraining from recommending vaccines for those under 5 years old (24, 25). Moreover, the risk of infectious disease transmission, including COVID-19, is significantly heightened within densely populated pediatric settings such as schools. In response to these concerns, this multicenter and retrospective study was conducted to analyze the demographic and clinical characteristics of children with COVID-19 in Mazandaran province. Furthermore, our study aimed to evaluate the case severity and identify risk factors influencing ICU admissions.

In this study, the demographic and clinical presentations of confirmed or probable pediatric COVID-19 were reported. These patients sought medical attention over six months, coinciding with the second and third waves of the pandemic in Iran. During these waves, variants such as B.1.1.7 (Alpha in the WHO classification), B.1.351 (Beta), and B.1.617.2 (Delta) were predominant, while more recent variants like Omicron had not yet emerged. The Delta variant likely led to a higher pneumonia rate, more severe disease, and increased mortality compared to other variants. However, analysis of laboratory test results did not show significant differences between variants in children (17, 28). None of the children were vaccinated during this period, but vaccination programs had been initiated for adults.

The median age of our patients was 6 years. The majority of children with COVID-19 in our study were mild to moderate, aligning with findings from other research studies (29–33). With increasing age, the hospitalization and the severity of the disease decreased. Nevertheless, approximately half of our hospitalized patients were over 5 years old. This finding is consistent with previous studies (16, 22, 34). Male gender was slightly more prevalent (1.17:1), and its frequency was a bit higher in the severe/critical group. Similar ratios have been observed in some other studies and across newborns and adults (3, 9, 16, 34–38).

Along with other studies, fever and cough were the most prevalent symptoms in our study (4, 16, 36, 39–41). Contrary to previous reports, fever was significantly more prominent in our study (37, 42, 43). In some studies, including one involving 6,610 hospitalized children with COVID-19 in Iran, dyspnea was reported as the third common symptom, supporting our findings (4, 37, 44).

After adjusting for the impact of other factors, the presence of underlying diseases, gastrointestinal symptoms, and obesity significantly increased the risk of ICU admission by 4.16, 3.10 and 2.17 times, respectively. Notably, besides ICU admission and the need for oxygen therapy, none of the other factors emerged as a risk factor for the severity of the disease. Assessing factors influencing mortality was challenging due to the limited number of fatalities.

In our study, although the specific details of underlying medical conditions (aside from abnormal BMI) were not provided, the presence of such conditions showed a significant association with the development of severe or critical disease. Furthermore, having an underlying medical condition independently increased the risk of ICU admission by more than 4-fold. This finding aligns with some prior studies, consistently highlighting underlying medical conditions as an established risk factor (36, 45).

Obesity is a known risk factor for COVID-19 (45–47). In this study, data on height and weight were available for half of the patients, in which 36.25% had a BMI above the normal range. The majority of the mild (outpatient) cases had normal BMI. O'Neill et al. reported obesity as the most significant risk factor for hospitalization, followed by diabetes (45). A lower BMI correlated with increased hospitalization, appears to have no association with the severity of the disease. One possible explanation for the impact of a low BMI was observed in the study by Crespo et al., where circulating CD3, CD4 and B lymphocytes were found to be lower in underweight children (41).

Among hospitalized patients, the ICU admission and mortality rates were 19.77% and 0.91%, respectively. Large reports from Iran indicated a significantly higher mortality rate in children, with inpatient mortality of 2.9%–5.3% in various studies (7, 37). Moreover, ICU admission rates in these studies were 14.5% and 13%, which are lower compared to our study (7, 37). Apart from methodological differences, this variation might stem from a better understanding of the presentation and management of the new disease one year after its emergence. Moreover, a well-established referral system existed in the province, facilitating the identification and transfer of severe or critical cases to referral centers. In these centers, the threshold for ICU admission was lower, and patients were admitted to the ICU earlier if possible.

In our hospitalized patients, 61 (6.97%) were diagnosed with MIS-C, constituting 37.5% (3 individuals) of our overall mortality. In a systematic review, 11.28% of examined children exhibited symptoms consistent with MIS-C (48). However, a single-center long-term study in Mexico reported a 0.6% prevalence of MIS-C (36). Therefore, MIS-C is recognized as one of the most severe consequences/presentations of COVID-19, demanding vigilant attention from the healthcare team. In our study, 4.91% of MIS-C patients succumbed to the illness. A similar study in Iran reported a 5.99% mortality rate in children, indicating comparable findings (3).

In conclusion, our study emphasized the critical significance of understanding the severity and clinical presentation of pediatric patients with COVID-19, shedding light on key symptoms and risk factors for severe illness. While fever, cough, and dyspnea remained prevalent symptoms, our findings suggested a relatively low mortality rate among pediatric patients. However, underlying comorbidities, obesity, and gastrointestinal symptoms independently correlated with ICU admission, emphasizing the need for early intervention and monitoring. In addition, our analysis highlighted the role of BMI in disease severity and hospital admission. Moving forward, vaccination efforts and targeted interventions are important in protecting vulnerable pediatric populations and reducing the burden on healthcare systems.