Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

Abstract

Background Coronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19. Methods This systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection. Results Among 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19. Conclusion Children with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.

Clinical Factors Associated with COVID-19 Severity in Chronic Hospitalized Infants and Toddlers: Data from a Center in the West Part of Romania

“…In the study presented, the majority of infected children were males (M/F: 3.2/1.0), but half of the girls developed a severe outcome. In our relatively small group, the male gender was not a risk factor for severe COVID-19 disease, as also stated in other papers [4,25].…”

“…The effect of prematurity was evaluated among children younger than 2 years of age in several studies [24,25]. They concluded that the risk of severe infection was two-fold higher in premature infants than in full-term infants (RR, 2.00; 95% CI, 1.63-2.46) [25].…”

“…The effect of prematurity was evaluated among children younger than 2 years of age in several studies [24,25]. They concluded that the risk of severe infection was two-fold higher in premature infants than in full-term infants (RR, 2.00; 95% CI, 1.63-2.46) [25]. However, these results were not confirmed by our results, where most premature babies (11 of 18) remained negative and just two children developed severe symptoms.…”

Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age

“…Previous studies have shown higher risks of severe Covid-19 and admission to an intensive care unit among children with coexisting conditions, 26 , 27 but we could not assess this because data were not available in the national Covid-19 vaccination registry. Nonetheless, the prevalence of coexisting conditions predisposing children to severe Covid-19 is probably low in this age group.…”

Air pollution might affect the clinical course of COVID-19 in pediatric patients

“…However, studies show that other air pollutants, i.e., nitrogen oxides and ozone, may also affect the COVID-19 severity and mortality ( Mele et al, 2021 , Khorsandi et al, 2021 , Achebak et al, 2021 ). One should also note that the present investigation did not include the potential differences in socioeconomic factors, health behaviors (e.g., physical activity) and presence of comorbidities (e.g., chronic lung disease, diabetes, heart disease, immune deficiencies, seizure disorders, obesity,) that may affect the susceptibility of children to COVID-19 ( Choi et al, 2022 , Størdal et al, 2022 ). Moreover, the patient data were collected over 17 months, during which various SARS-CoV-2 variants emerged and dominated ( Hryhorowicz et al, 2021 , Jabłońska et al, 2021 ).…”