key: cord-0771135-5tmcbomt authors: Zhang, Zhen‐Zhen; Chen, Da‐Peng; Liu, Quan‐Bo; Gan, Chuan; Jiang, Li; Zhu, Kun; Zhang, Xia‐Yi; Xu, Hong‐Mei; Huang, Ai‐Long; Long, Quan‐Xin; Deng, Hai‐Jun; Chen, Juan title: Clinical features of Chinese children with COVID‐19 and other viral respiratory infections date: 2021-10-21 journal: Pediatr Pulmonol DOI: 10.1002/ppul.25700 sha: 5d29a70f08e9a587288e1bf5bb2b381e58bfe0ad doc_id: 771135 cord_uid: 5tmcbomt OBJECTIVE: Few studies have explored the clinical features in children infected with SARS‐CoV‐2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID‐19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID‐19 positive, 58 patients with ARTI, and 20 age and sex‐matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID‐19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one‐third of patients in the COVID‐19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID‐19 group had lower white blood cells, platelet counts as well as a neutrophil‐lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID‐19 group than in healthy individuals. Seven cytokines (IL‐1Ra, IL‐1β, IL‐9, IL‐10, TNF‐α, MIP‐1α, and VEGF) changed serum concentration in COVID‐19 compared with other ARTI groups. CONCLUSION: Patients with COVID‐19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID‐19. The coronavirus disease-2019 infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) caused a global pandemic. 1 The clinical spectrum of COVID-19 varies from asymptomatic carriers to severe pneumonia characterized by acute respiratory distress syndrome (ARDS) and multiorgan failure with mortality. [2] [3] [4] Emerging evidence suggests that older age, male, obesity, and comorbidities such as diabetes, and cardiovascular diseases, are major risk factors among patients with COVID-19. 5, 6 Although both adults and children are vulnerable to SARS-CoV2, children are relatively spared from this disease, with significantly reduced prevalence, severity, and mortality. The potential mechanisms of this disparity remain to be clarified. The entry of SARS-CoV-2 into host cells relies upon the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor and the priming of the S protein by host proteases, such as TMPRSS2. 7 Therefore, one hypothesis is that reduced viral entry and replication in the lung resulted in mild symptoms in children. However, several studies have discovered similar viral load in children and adult. [8] [9] [10] Furthermore, recently another study compared the mRNA level of ACE2 and TMPRSS2 in nasal mucosa between children and adults, which showed that the expression of ACE2 and TMPRSS2 was not correlated with age and viral infection. 11 The role of the SARS-CoV-2 receptor in pediatric COVID-19 needs further study. Another plausible theory is that children might have a distinct response to SARS-CoV-2 compared to adults, attributed to the differences in the composition and functional responsiveness of the immune system. 12, 13 Recently, Suratannon All continuous variables were described as mean with standard deviation (SD), while categorical characteristics were described as counts and percentage (%). Mann-Whitney U test was applied for comparison between two groups, and analysis of variance (ANOVA) was used to compare COVID-19 and ARTI groups, respectively. p < 0.05 was considered statistically significant, and p < 0.001 was considered highly statistically significant. Statistical analysis was performed using the R software, version 3.6.0. There was a significant difference between COVID-19 and other ARTI in demographic features and clinical manifestations (Table 1 ). In general, patients with COVID-19 were older and showed milder symptoms and disease severity than the other three groups. The median age of the COVID-19 group was 14.5 years (0.64-17.0 years). All patients in the COVID-19 positive group were either asymptomatic or showed mild infection. In contrast, two (10.53%) cases in the RSV group, four (21.03%) cases in the FLU group, and five (25%) cases in the ADV group showed moderate to severe symptoms respectively, and four (20%) patients in the ADV group showed severe disease after infection. As to clinical symptoms, cough and fever were the most frequent symptoms of all four groups. Except for the COVID-19 group, patients in the other three groups had high fever with peak body temperature exceeded 39°C. In addition, dyspnea, wheezing, and diarrhea were absent in the COVID-19-infected group but common in the remaining three groups. Next, we compared the peripheral blood abnormalities among the four groups. There were significant differences between the COVID-19-infected and other groups in white blood cells (WBC), platelet (PLT) counts as well as neutrophil-lymphocyte ratio (NLR). Albeit there was no statistical significance of the C-reaction protein (CRP) and procalcitonin (PCT) level, the ARTI resulting from RSV, IVA/B, and ADV showed a higher rate of CRP(>8 mg/L) and PCT (>0.25 ng/L) level. These results suggested that the inflammation response was stronger in ARTI caused by RSV, IVA/B, and ADV. Finally, we compared the radiology characteristics of different pathogens. For most patients with COVID-19, there were few positive lesions observed through radiology exam, and ground-glass opacity (GGO) was the main finding ( Figure 1A,B) . By contrast, patients with other ARTI showed extensive injuries, including consolidation, tree-in-bud sign, extensive interlobular septa thickness mosaic signs ( Figure 1C-H) . Taken together, SARS-CoV-2 is prone to affect the school-age and adolescents, with milder symptoms and lower inflammation response compared to other respiratory pathogens. Since children with COVID-19 showed mild disease with normal laboratory tests, we speculate the inflammatory reaction might be mild or absent in patients with these mild cases. We first compared the circulating cytokines levels in COVID- 19 Figure 3H ; Table S1 ). These results suggested a stronger inflammation with more cytokines perturbed in the ARTI groups, especially in the FLU and ADV subgroup. Cytokines dysregulated children infected with SARS-CoV-2. Blood samples were collected from pediatric patients with COVID-19 and healthy children match with age and sex [Color figure can be viewed at wileyonlinelibrary.com] REFERENCES 1. 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