Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread globally since its emergence in late 2019 (Baker et al., 2022). As the virus continues to mutate, different COVID-19 variants have emerged with varying characteristics. The Omicron variant (B.1.1.529), first identified in South Africa in November 2021, became the predominant strain during the fourth wave of the global COVID-19 pandemic (World Health Organization, 2021). The Chinese government implemented strict epidemic control measures, including the “zero COVID” policy, which remained in effect until December 2022. After the zero-tolerance policy on COVID-19 ended in 2022, China experienced a widespread COVID-19 epidemic driven by the Omicron variant (Chinese Center for Disease Control and Prevention, 2023). Between December 2022 and February 2023, the cumulative number of confirmed cases increased by approximately 89.4 million, bringing the cumulative total to 99 million in China (World Health Organization, 2023a). During this period, all locally transmitted SARS-CoV-2 cases were confirmed to be caused by the Omicron variant according to the Chinese Center for Disease Control and Prevention.

Studies have shown that while the Omicron variant is more transmissible than previous variants, it is generally associated with lower disease severity and a reduced incidence of multisystem inflammatory syndrome in children (MIS-C) (Tian et al., 2022; Wang et al., 2022; Whittaker et al., 2022; Wolter et al., 2022; Choi et al., 2023; Ross et al., 2023; Wang et al., 2023). However, extra-pulmonary organ involvement, the need for invasive mechanical ventilation (IMV), and mortality rates in severe and critical cases have not significantly decreased (Corriero et al., 2022; de Prost et al., 2022). The high transmissibility of Omicron led to an increased medical burden on both adult and pediatric healthcare systems. Studies have reported a rapid rise in pediatric SARS-CoV-2 infections and hospitalizations during the first Omicron wave (Cloete et al., 2022; Menni et al., 2022). Although most pediatric cases are mild to moderate, some children develop severe illness requiring intensive care unit (ICU) admission (Bhalala et al., 2022; Uka et al., 2022; Zhang et al., 2023). There is limited research on children who have experienced severe or critical illness due to first-time infection with the Omicron variant.

In this study, we investigated children with severe and critical COVID-19 who were admitted to the pediatric ICU (PICU) of the National Regional Medical Center in Northeast China during the first Omicron epidemic and explored factors associated with poor outcomes.

In this study, we described the clinical characteristics of severe and critically ill children diagnosed with the first wave of SARS-CoV-2 Omicron infection who were admitted to the PICU of the National Regional Children’s Medical Center in Northeast China. Our findings indicate that chest CT score based on CO-RADS, serum AST levels at admission, and the PELOD-2 score may predict adverse outcomes in this specific population.

Our data showed that 61% of severely and critically ill children were younger than 3 years old. A statistical analysis of children in France with acute COVID-19 infections in the PICU found that 45.1% of patients were aged <2 years (excluding those under 1 month), while 60.7% were aged <5 years (Recher et al., 2023). Similarly, a British study reported that 61% (36/59) of PICU patients were aged <5 years (Ward et al., 2023). With the emergence of the Omicron variant, mathematical modeling and quantitative analyses of empirical data predict that first-time infections may occur at younger ages due to rising population immunity from prior Omicron infections and vaccination efforts (Koelle et al., 2022). A plausible explanation for this trend is that children aged <3 years remain unvaccinated (Tachikawa et al., 2025), making them more vulnerable to severe initial infections and increasing likelihood of requiring PICU admission.

Comorbidities have been consistently associated with severe SARS-CoV-2 infection in pediatric populations, with studies reporting that 15.6% to 83% of pediatric patients have at least one pre-existing condition across various cohorts (Ungar et al., 2023; Kulkarni et al., 2024). Our study aligns with this range, revealing that 24% of patients had comorbidities, with 13% requiring IMV and 8% receiving non-IMV. Although the clinical symptoms of Omicron infection are mild in the vast majority of healthy children, those with comorbidities may experience further deterioration of underlying conditions and a decline in quality of life (Dryden et al., 2022; Jassat et al., 2023; Calcaterra et al., 2024). Compared to the Alpha variant, the Omicron group had a higher prevalence of comorbidities, worse initial laboratory data, and higher in-hospital mortality rates (40.6% vs 15.2%, p = 0.004). The Charlson Comorbidity Index was identified as an independent risk factor for in-hospital mortality (Cheng et al., 2025). These findings highlight the heightened risk of adverse outcomes in pediatric patients with comorbidities, emphasizing the need for closer monitoring and targeted interventions.

At admission, 25 children (66%) were diagnosed with respiratory failure, and four (16%) developed ARDS. A previous study in southern China (Guangdong) supports our findings (Lin et al., 2024b). Similarly, research on critically ill adults and children in the northeastern United States (New York) found that 90% of patients who developed ARDS initially presented with dyspnea (Derespina et al., 2020). Accurate identification of these presentations, combined with the early administration of respiratory support, may improve patient outcomes by minimizing disease progression and alleviating stress in healthcare facilities (Mizuno et al., 2023). Initial studies during the pandemic linked respiratory system impairment at hospital admission to adverse outcomes with ARDS, serving as an independent predictor of disease severity (Ni et al., 2024). Some research suggests that COVID-19 comorbidities increase with latitude, but we found no evidence to confirm an association between geographic location and complications or comorbidities in children.

COVID-19 is known to cause neurological complications (Bhalala et al., 2022). Studies report that approximately one-third of hospitalized children with Omicron infection experience neurological disorders, such as convulsions (Choi et al., 2023; Tang L. et al., 2024), with higher incidence rates in severe cases (LaRovere et al., 2023). A study by Lin et al. found that 70% of critically ill children with SARS-CoV-2 Omicron infection (Lin et al., 2024b) developed encephalopathy. Among the cohort, 21 (55%) had neurological complications, with convulsion being the most common manifestation (39%). However, we could not determine whether SARS-CoV-2 infection was the primary cause of these neurological symptoms. There are some potential pathogenic mechanisms of SARS-CoV-2 infection affecting the central nervous system (CNS): direct invasion of the CNS, excessive release of pro-inflammatory cytokines, and the immune escape effect of the virus (Viviani et al., 2003; Hautala et al., 2021; Kurd et al., 2021; Shi et al., 2023).

In our study, 12 patients had abnormal head MRI findings. A single-center study conducted in the United States found that the most prevalent imaging findings among adults were nonspecific white matter microangiopathy (55.4%), chronic infarcts (19.4%), acute or subacute ischemic infarcts (5.4%), and acute hemorrhage (4.5%) (Radmanesh et al., 2020). Additionally, a study focusing on ICU patients in France reported that 23% (6/26) of patients experienced cerebrovascular events (Cleret de Langavant et al., 2021). Research in South China involving children supports our findings, indicating that all cases exhibited bilateral involvement, particularly in the thalamus and basal ganglia (Lin et al., 2024a). Possible reasons for these differences in brain involvement or clinical manifestations may relate to age and cardiovascular risk factors (Lu et al., 2024), or the likelihood of children developing acute necrotizing encephalopathy may be higher (Karami et al., 2023). Multicenter cohort studies on the adverse neurological functional outcomes and exploring factors are needed.

Our research shows that chest CT score is associated with the need for IMV in severe and critically ill children. Li et al. did not calculate chest CT scores but described CT findings of consolidation, linear opacities, crazy-paving pattern, bronchial wall thickening, high CT scores, and extrapulmonary lesions as features of severe or critical COVID-19 pneumonia (Li et al., 2020). A study conducted in Brazil on non-invasive respiratory support and IMV concluded that alternating non-invasive respiratory support with HFNO increased IMV rates, regardless of comorbidities and chest CT scores among patients with COVID-19. The chest CT scores were significantly different among all groups (da Cruz et al., 2024). For immunocompromised patients, the total chest CT score was associated with longer hospitalization and ICU admission (Ghadery et al., 2024). Compared with prior studies, the results in our cohort accurately predicted the need for IMV in severe and critically ill children with first-time Omicron infection. Our findings further support the predictive value of chest CT scores for IMV requirements, which could be enhanced by combining CT analysis with other clinical parameters (Orlandi et al., 2021). The results above suggest that the chest CT score based on CO-RADS could be an important factor in predicting poor outcomes for severe and critically ill children.

The study showed that PELOD-2 and serum AST levels ≥52.5 U/L at admission were associated with increased mortality or prolonged PICU stays. A multi-center survey on prolonged mechanical ventilation (MV) showed that the use of vasoactive agents and higher PELOD-2 scores at the time of the prolonged MV diagnosis were significantly associated with an increased risk of prolonged MV-related death. Meanwhile, early rehabilitation intervention was identified as crucial for improving patient outcomes (Zhang et al., 2024). Several studies used the PELOD-2 to predict mortality and prognosis (El-Nawawy et al., 2017; Schlapbach et al., 2018; Lee et al., 2022). These findings suggest that the predictive power of PELOD-2 may vary across specific subpopulations.

The results of this study indicated that abnormalities in various laboratory indicators were more pronounced in critically ill children within the IMV group. Notably, serum AST levels were a predictor of PICU duration. Other indicators included CK-MB isoenzyme (µg/L) ≥10, IL-6 ≥20 pg/mL, and coagulation indices (PT, INR, D-dimer). Early Omicron infection may induce subclinical cholangiocyte damage through a multifactorial and complex pathogenic process, differing from earlier strains of SARS-CoV-2 (Iheanacho and Enechukwu, 2022). Cao et al. (2024) observed that patients with abnormal liver enzyme levels exhibited significantly elevated inflammatory markers, including PCT, IL-6, and CRP. IL-6, as an inflammatory factor, may be attributed to stress responses in the liver, characterized by the release of major acute-phase cytokines in response to Omicron infection (Dufour et al., 2022). A study on adenovirus (ADV) infection found that AST levels were also associated with longer hospital stays in children (Tang S. et al., 2024). Based on these findings, serum AST levels can be considered a reliable indicator of prolonged PICU stays.

This study has some limitations. First, the relatively small sample size might limit the generalizability of our conclusions to patients in other regions. Second, since this was a retrospective study, potential biases and confounding factors might have influenced the results. Additionally, long-term follow-up data were not collected. Finally, standardized scores were not used to assess disease severity in patients, which should be considered in future research.

Respiratory failure and COVID-19-associated neurological disorders are major complications in severe and critically ill children with first-wave SARS-CoV-2 Omicron infection. Chest CT score based on CO-RADS may predict severe and critically ill children with SARS-CoV-2 Omicron infection requiring intensive mechanical ventilation. Additionally, serum AST levels at admission and the PELOD-2 score may predict prolonged PICU stays and mortality, helping to avert the development of potentially life-threatening complications.