Discussion

The first series of cases reported in China included 2135 children under 18 years of age with COVID-19,1 17 of whom 870 (40%) were less than 6 years old; of these, 379 (43.5%) were under 1 year of age. In our study, 204 641 children under 18 years of age were registered with COVID-19 (cumulative incidence of 516.2 per 100 000 children under 18 years of age), of whom only 2.9% were under 1 year of age, with the highest percentage of cases falling in the 10–17 years age group. The number of SARS-CoV-2-positive children under 18 years of age in Mexico increased substantially during December 2020 and January 2021, and during July and August 2021, which can be explained by an increased circulation and transmission of the virus, as has been seen in other countries. In the database used for this study, 51.8% of children under 18 years of age had a history of contact with another SARS-CoV-2-positive case, which contrasts with a study in Switzerland,31 where in 79% of households, one or more adults in the family had suspected or confirmed COVID-19 before the onset of symptoms in children. This difference may be attributable to the lack of an intentional case finding and contact study.

COVID-19 in children usually starts with mild respiratory symptoms, the main ones being fever, cough and irritability, followed by sneezing, rhinorrhoea, nasal congestion or even gastrointestinal symptoms7 9–12 20 21 24 26 28 32 for 2 or 3 days,6 and it has been reported that most children are in the early stages of the disease when they are hospitalised.16 According to data from the US Centers for Disease Control and Prevention (CDC), between 0.6% and 8.9% of COVID-19 cases in children under 18 years of age13 are hospitalised13 and only 1.5% (310 out of 20 133) of patients under 18 years of age in a report from the UK were hospitalised.14 When comparing these data with ours, we found a similar percentage (4.6%) as in the USA, contrary to that reported in a study in Madrid, where 60% of children with COVID-19 were hospitalised.33 According to a study in China in which more than 2000 children with COVID-19 were analysed, more than 90% of them were asymptomatic or had very mild symptoms; however, the youngest children were those who mainly required hospitalisation.1 17 In the case of Mexico, the percentage of children with COVID-19 under 1 year of age requiring hospitalisation was 35.3% and only 2.6% of those older than 10 years (table 1); even more, almost half of hospitalised children with COVID-19 were less than 6 years old. Also, as has been observed during the pandemic, males are hospitalised more frequently.

A systematic review and meta-analysis of 31 studies including 1181 children under 5 years reported that 49% of children who required hospitalisation (moderate/severe disease) required oxygen therapy (not inclusive of mechanical ventilation).34 In our study, one-third of hospitalised children had pneumonia and most of them (40%) were children aged 10–17 years; despite this, the proportion of children with pneumonia who required intubation and mechanical ventilation was very similar in children under 1 year of age and adolescents (table 2). This study also found that pneumonia substantially increases the probability of hospitalisation, and that it increases even more with age.

Other causes of hospitalisation related to COVID-19, such as multisystem inflammatory syndrome (MIS-C), have been identified in other studies; no cases of MIS-C were identified in the data source consulted for this analysis.

Regarding the need for intensive care, the US CDC Morbidity and Mortality Report (January 2021) reported that of 1 222 023 confirmed cases of COVID-19 in children under 18 years of age, 2.3% were hospitalised, 0.8% required ICU care and the case fatality was less than 0.1%.35 A systematic review of 31 studies reported that 7% of cases in children under 5 years were severe cases requiring ICU34; a European multicentre study reports that 8% of SARS-CoV-2-positive children required ICU admission and 4% required mechanical ventilation.10 By contrast, a study of paediatric ICUs in the USA and Canada reports that 38% of patients admitted to the ICU required invasive ventilation.36 In this analysis, we found that 8.4% (1034) of hospitalised children required ICU care, from which 64.7% were under 6 years of age. If only patients admitted to an ICU are considered, 79.5% (823/1034) were intubated; of them, one-third were children under 1 year and one-third were adolescents (table 2); also relevant is the finding that 39% of children intubated for a disease different from pneumonia were less than 1 year old, which could be related with the prevalence of respiratory and cardiovascular diseases in this age group.

The severity of COVID-19 depends on several factors. A multicentre study in Europe found that being male, being less than 1 month old, a pre-existing medical condition, as well as signs of lower respiratory infection were associated with ICU admission.10 It has been reported that approximately one-quarter of infected children may have associated diseases7 10 27 32 such as congenital heart disease, blood disorders, immunosuppression, chronic kidney, liver or lung disease,2 11 15 32 suggesting that these conditions lead to an increased risk of developing a severe form of the disease.2 11 26 37 38 In a systematic review, among 9353 paediatric patients with SARS-CoV-2 infection and underlying comorbidities, 481 (5.1%) had severe COVID-19 and/or were admitted to an ICU. In contrast, only 579 of the 275 661 (0.21%) pooled paediatric patients without comorbidities had a severe manifestation of COVID-19.39 However, a study of 260 children hospitalised in Wuhan in March 2020 reports that the likelihood of comorbidities was not different between the severe and non-severe COVID-19 groups,40 and even children with comorbidities who tested positive for SARS-CoV-2 had a good prognosis.41 According to US CDC data from January 2021, up to 27.6% of children aged 0–17 years with SARS-CoV-2 infection had a concomitant illness; the most prevalent were chronic lung disease (6%), other (2%) and disability (1.1%).35 An analysis of nationwide data from paediatric cases in Mexico reported that obese children were 39% more likely to have SARS-CoV-2 infection, and surprisingly, an Italian study reported a much lower prevalence of asthma in their paediatric COVID-19 cohort than in the general population (2% vs 11%).42 It has been reported that obesity was the most common comorbidity among hospitalised COVID-19-positive children, with a significant association between obesity and severe cases requiring mechanical ventilation in children 2 years and older.42 In addition, the number of comorbidities (one, two, or three or more vs none) increased the risk of death (0.60 (0.42–0.85)), as did all the main specific pre-existing medical conditions.43

In this study, we found that a pre-existing medical condition increases the probabilities of hospitalisation; pre-existing medical conditions and increased probability of being hospitalised varied with age group. In general, we can say that older children, who have higher prevalence of chronic diseases, have more probabilities to be hospitalised due to COVID-19. The lack of information regarding ‘other comorbidities’ and that these increase the risk of hospitalisation is worth noting.

It has been reported that paediatric deaths from COVID-19 are extremely rare,19 36 44 as shown in a report as of February 2021 with data in children aged 0–19 years from France, Germany, Italy, Korea, Spain, England and the USA, where 259 deaths occurred, for a mortality rate of 0.19 per 100 000.23 In our country, 934 deaths were recorded in children under 18 years of age in approximately 18 months’ follow-up period, which is equivalent to a mortality rate of 2.35 per 100 000 children under 18 years of age, a rate 12 times higher than the above-mentioned report. By contrast, the overall mortality rate for COVID-19 in Mexico for the same period was 234.4 per 100 000 people.45 Six hundred and twenty-five children who died were diagnosed with pneumonia, which represent 12.8% of total pneumonia cases due to COVID-19 in this age group for the study period; it also represents 66.9% of all deaths. For the same study period, it is recorded that 73% of deaths due to COVID-19 in adults in Mexico involved pneumonia, and up to 42% of all cases of COVID-19 pneumonia died.29

Regarding risk of death, age per se is identified as conferring a higher risk of death in children under 1 year of age (OR 10.59), which agrees with a study that mentions that age under 1 year and the presence of underlying conditions represent serious risk factors.46 The overall case fatality rate for COVID-19 has been reported to be 3% (0%–29%); however, it varies among countries and among different age groups.47 In children under 18 years of age, rates of 0%–0.03% have been reported, and in populations aged 85 years and older, rates of up to 30.5% have been reported.48 In a recent study in patients younger than 20 years with COVID-19 in Brazil, the estimated probability of death was 4.8% during the first 10 days after hospital admission, 6.7% during the first 20 days and 8.1% at the end of follow-up. Risk of death was increased in infants younger than 2 years (HR 2.36; 95% CI 1.94 to 2.88) and adolescents aged 12–19 years (HR 2.23; 95% CI 1.84 to 2.71) relative to children aged 2–11 years.43

The present study shows that, nationally, the COVID-19 case fatality in children under 18 years of age is 0.4%, and varies significantly by age, being 4.2% in children under 1 year, 0.8% in children 1–5 years and 0.2% in children 6–9 and 11–17 years (table 1). Age less than 1 year old, presence of pneumonia, being adolescent from an indigenous community, other comorbidities, immunosuppression, cardiovascular disease, high blood pressure, diabetes, obesity and chronic renal disease increase the probability of death in the studied population. Interestingly, we also found that the probability of death due to pneumonia increases with age. Another study that includes only Mexico City reported the relative risk attributable to the presence of comorbidities was highest among children and adolescents, comorbidities being accountable for 80%–98% of the age-specific mortality. In children under 10 years of age, comorbid conditions associated with increased mortality were mainly those coded as ‘other comorbidities’. In those between 11 and 20 years old, diabetes, obesity, immunosuppression and chronic renal disease were the most significant associated factors.49

In our country, the age group with the highest number of hospitalisations and deaths due to COVID-19 was children under 1 year of age. It is noteworthy that the higher the age, the lower the proportion of hospitalisations and deaths (table 1, figure 1).

The most important limitation of this study is the impossibility to verify the correct and complete registry of comorbidities, so it is possible that its prevalence is underestimated or overestimated, which can modify the real influence of a disease in the probability of hospitalisation and death.