Analysis of clinical characteristics and risk factors of influenza-related deaths in children

Abstract

Objective: To explore the clinical characteristics and risk factors of influenza-related deaths in children and to raise awareness of the disease among clinicians. Methods: Clinical data of 31 influenza-related deaths hospitalized in Pediatric Intensive Care Unit (PICU) of Shenzhen Children's Hospital from January 2009 to December 2019 (death group) were retrospectively analyzed. A control group enrolled 188 patients with severe influenza who were successfully cured and hospitalized in PICU at the same time. Independent Student's t test, Mann-Whitney U test and chi square test were used to compare the general conditions, clinical manifestations, laboratory tests and antiviral therapy between two groups. Risk factors of mortality in children with severe influenza were identified by multivariate Logistic regression. Results: In a total of 219 cases with severe influenza, 31 cases progressed to influenza-related deaths, 19 males and 12 females, with age of (4.2±3.3) years; 29 cases had influenza A virus infection and 2 cases had influenza B virus infection. Deaths occurred more in winter and spring (23/31). Eight patients had underlying diseases. In 188 patients who were successfully cured, 138 were males and 50 females, with an average age of (3.4±2.7)years. There were 151 patients with influenza A virus infection, and 37 patients with influenza B virus infection. Twenty patients underlying diseases. None of the patients in the death group has received the influenza vaccine within 1 year before infection. Common symptoms were fever (n=31), cough (n=21), and seizures (n=17) in the death group. The complications were influenza associated encephalopathy (IAE) (n=17), pneumonia (n=17), plastic bronchitis (n=1), air leak syndrome (n=3), acute respiratory distress syndrome (ARDS) (n=8), and multiple organ dysfunction syndrome (n=24). In the death group, 13 patients had secondary infections, of whom 9 cases had gram-positive Cocci infection. Complete blood count of the patients showed that white blood cells count increased in 15 cases and the lymphocyte count decreased in 13 cases. Meanwhile, high sensitivity C-reactive protein increased in 18 patients. All the 31 patients in the death group were treated with neuraminidase inhibitors for antiviral therapy, of whom 24 cases received the first dose 48 h after fever (late neuraminidase inhibitor (NAI) treatment). The causes of death in 31 patients were further analyzed, including 23 cases died of influenza complications, 4 cases died of underlying diseases and 4 cases died of secondary infections. Compared with the control group, the death group had more underlying diseases (25.8% (8/31) vs. 10.6% (20/188), χ²=4.215, P=0.040), higher incidence of secondary infection (41.9% (13/31) vs. 20.2% (38/188), χ²=7.029, P=0.008), and more late NAI treatment (77.4% (24/31) vs. 53.7% (101/188), χ²=6.099, P=0.014). Logistic regression analysis showed that secondary infection, late NAI treatment, complicated with ARDS and IAE were risk factors for death of patients with severe influenza (all P<0.05). Conclusions: Influenza can cause multi-system disorder, especially lung infections and IAE. It can improve the success rate of treatment for children with severe influenza, identification and early treatment of secondary infection and complications, and timely administration of NAI treatment.