Introduction
Influenza is an infectious respiratory disease caused by influenza A and influenza B viruses; it often occurs in outbreaks during the cold season and can cause serious consequences and even death.1,2 Young children, the elderly, and people with underlying medical conditions are particularly vulnerable.3–6 It was estimated that annually there were between 291,243 and 645,832 deaths worldwide. due to seasonal influenza during the period 1999–2015, and in this time period the annual global respiratory mortality associated with influenza among children under 5 years of age ranged from 9,243 to 105,690.7.
There was a significant decrease in influenza activity worldwide during 2020 and 2021 following the onset of the COVID-19 pandemic. strain) viruses responsible for more than 99% of cases.8 Not surprisingly, influenza B viruses (Victoria strain) were detected in the vast majority of children with influenza we treated between late 2021 and early 2022. Before of the COVID-19 pandemic, Cocirculation of Victoria and Yamagata strains of influenza B or dominance of the Yamagata B lineage was reported in some regions.15–17 Influenza can cause a substantial increase in ambulatory visits, hospitalizations and deaths among children. Recognizing the factors that contribute to the severity of influenza is key to improving treatment and reducing morbidity and mortality.3 The aim of this study was to identify factors associated with the severity of illness in children with influenza infection. influenza B virus during the COVID-19 pandemic, which has been sparsely described in the literature.
methods
Ethical approval
This study was approved, with approval no. 202012, by the Medical Research Ethics Committee of the Children’s Hospital of Hebei Province, in accordance with the principles of the Declaration of Helsinki, the Code of Ethics of the World Medical Association. As this study is retrospective, presenting no risk of harm to subjects, and all patients are de-identified, the Committee waived informed consent.
Study subjects
Children (under 18 years of age) admitted to our hospital from December 2021 to January 2022 and diagnosed with influenza B were included in this study. Patients who tested positive for COVID-19 were excluded. Demographic data, clinical characteristics, underlying medical conditions, laboratory test results, and treatment outcomes were retrieved and analyzed retrospectively.
Laboratory tests
Laboratory tests were performed in our Diagnostic Laboratory following the established protocols.
Detection of pathogens
A multiplex PCR-based platform, namely the ResP-CE system, was used to simultaneously detect the following pathogens: influenza A virus, influenza B virus, respiratory syncytial virus (RSV), adenovirus (ADV) , parainfluenza virus (PIV), human virus. rhinovirus (HRV), human metapneumovirus (HMPV), human bocavirus (HBOV), human coronavirus (HCOV), Chlamydia and Mycoplasma pneumoniae (MP). Multiplex PCR was performed as described elsewhere.18 Culture of respiratory secretions and blood samples for bacteria and fungi was done according to established protocols in our diagnostic laboratory.
Disease diagnosis and severity classification
Illness diagnosis and severity classification (severe or critical) were conducted according to the Chinese Expert Consensus on the Diagnosis and Treatment of Influenza in Children (2020 edition).19 The diagnosis was made if reported one of the following test results: 1) positive amplification of influenza B virus genomic nucleic acids by RT-PCR; 2) positive culture of influenza B virus; and 3) a ≥ 4-fold increase in serum influenza B virus-specific IgG antibody titer. Severe influenza was determined if one or more of the following manifestations were present: 1) body temperature >40°C for 3 days or more with cough or chest pain; 2) dyspnea accompanied by cyanosis; 3) vomiting and/or diarrhea with dehydration; 4) altered consciousness such as drowsiness or seizure; 5) complicated pneumonia; 6) deterioration of the underlying disease; or 7) hospitalization. Critical influenza was defined as having one or more of the following conditions: 1) respiratory failure; 2) septic shock; 3) multiple organ dysfunction syndrome; 4) acute necrotizing encephalopathy; or 5) other conditions requiring intensive care.
Treatment and results
All patients were treated according to the Chinese Expert Consensus on Diagnosis and Treatment of Influenza in Children (2020 edition).19 Outcomes were recorded as recovered and discharged, improved and transferred to hospitals community members or dead.
Statistical analyses
All statistical analyzes were performed using SPSS 20.0 software. Data normality was determined using the Shapiro-Wilk test. Normally distributed data were expressed as mean ± standard deviation and analyzed using Student’s t test. Non-normal data were presented as median (first quantile, third quantile) and analyzed using the Mann–Whitney test. Categorical data were analyzed using Chi-square or Fisher’s exact test. A p value of less than 0.05 was considered statistically significant.
results
A total of 88 patients with a mean age of 48 months (range: 7-144 months) were included in this study. Of these patients, 73 had severe influenza B and 15 were critical. The demographic and clinical characteristics of the patients in the two groups are shown in Table 1. The age, sex ratio, peak and duration of fever and the percentage of patients. with underlying conditions in the two groups were not significantly different. A significantly greater proportion of patients with critical influenza had extrapulmonary complications (Table 1).
Table 1 Demographic data and clinical characteristics among serious and critical patients
Laboratory tests revealed that white blood cell counts were not significantly different between the two groups; however, a significantly higher percentage of neutrophils and a significantly lower percentage of CD4+ cells were observed in the critical group (Table 2). C-reactive protein (CRP) levels in the two groups were not significantly different; the critical group had substantially higher levels of procalcitonin (PCT) and lactate dehydrogenase (LDH) (Table 2). Although critically ill children had substantially higher serum alanine aminotransferase (ALT) levels, serum aspartate transferase (AST) levels were not significantly different between the two groups (Table 2). There were no significant differences in serum concentrations of IL-1β and TNF-β between children with severe and critical influenza (Table 2).
Table 2 Results of the laboratory tests
Bacterial coinfections occurred in 15 severe cases (15/73, 20.5%) and 7 critical cases (7/15, 46.7%). The percentage of patients with bacterial coinfection was significantly higher in the critical group (p = 0.033, Table 3). The most detected bacterium was Streptococcus pneumoniae with 7 in serious patients and 4 in critical patients. Viral coinfections were identified in 21 and 4 cases in the severe and critical groups, respectively (p = 0.999), with adenovirus being the most detected. There were 21 and 3 positive cases for Mycoplasma pneumoniae in the severe and critical groups, respectively (p = 0.751) (Table 3).
Table 3 Co-infections detected in serious and critical cases
Patients with critical conditions had a significantly longer hospital stay (Table 4). All children in the severe group recovered or improved, while four patients with an age range of 5 to 21 months died in the critical group (Table 4). Of these four patients, three had underlying medical conditions: one with developmental delay, one with asthma, and one with spinal muscular atrophy.
Table 4 Treatment results
discussion
Influenza B viruses are less common than influenza A viruses in most seasons and cause relatively milder forms of infection that are less studied.20 We witnessed the dominance of the Victoria B strain in the 2021-2022 winter season and the characteristics of influenza B have not been described in children during the COVID-19 pandemic. In this study, we examined disease severity and its associated factors in children with influenza B between December 2021 and January 2022, and reported the following main findings: 1) a greater proportion of children who were severely patients had extrapulmonary complications and bacterial coinfections. and 2) critically ill children had higher PCT and LDH levels, a higher percentage of neutrophils, and a lower percentage of CD4+ lymphocytes.
Influenza can cause complications outside the respiratory system in both adults and children.21–27 A large series study of 2330 pediatric patients hospitalized with influenza A (H1N1 pdm09) during the 2009–2010 pandemic in the USA revealed that 709 (30 .4%) children had complications affecting the digestive, neurological, musculoskeletal and cardiovascular systems.23 Several recently published articles have described extrapulmonary complications in children hospitalized with influenza B before the COVID-19 pandemic.24–27 Geerdes-Fenge et 17 hospitalized children were treated. with influenza B in northern Germany during the 2017–2018 winter season, and revealed that 5 (29.4%) suffered extrapulmonary complications,24 lower than the 42% (37/88) found in the present study (Table 1). A few studies focusing on neurologic involvement in children hospitalized with influenza B observed that approximately 10–15% of patients had neurologic complications.25–27 A study in Hong Kong found that 7.3% of children (672 /9175) between 2014 and 2018 had neurological complications.25 Frankl et al reported that, during 2010-2017, 12.9% of hospitalized children (53/412) at a US tertiary pediatric hospital had complications neurological.26 Mattila et al showed that 16.1% of hospitalized patients (18/112) in a university hospital in Finland…