Long COVID syndrome in children: neutrophilic granulocyte dysfunction and its correlation with disease severity

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BACKGROUND: Many children suffer from lingering symptoms after COVID-19, known as long COVID syndrome (LCS), otherwise called Post COVID-19 Condition (PCC). Despite extensive research, the prevalence of symptoms, its impact on quality of life, and underlying mechanisms still need to be fully understood. As neutrophilic granulocytes play an essential role in COVID-19, and their prolonged disruption was found to cause immunological diseases, we hypothesized their ongoing disturbed functionality in LCS. METHODS: We studied 129 children with LCS, 32 convalescent children (CG+), and 8 uninfected children (CG-). Online questionnaires and in-person examinations assessed symptoms, quality of life, and functioning (QoL-F). Effector functions of neutrophilic granulocytes obtained from the venous blood of 29 LCS and 17 CG+ children were also investigated. RESULTS: Persistent fatigue was the most common symptom in children with LCS, while both control groups complained about anxiety most frequently. LCS children experienced significantly more symptoms, impairing their QoL-F compared to CG+. Neutrophilic granulocyte dysfunction was found in LCS children, with decreased superoxide-producing activity and phagocytosis compared to CG+. The number of complaints of children with LCS correlated significantly with altered neutrophil effector functions. CONCLUSION: Neutrophil dysfunction in children with LCS may be part of the disease pathogenesis or a predisposing factor. IMPACT: Using online questionnaires validated during in-person medical examinations and including two different control groups, our study compellingly supports and adds to previous clinical observations in the field. Our study provides valuable insights into the prevalence and characteristics of pediatric LCS, highlighting the significant quality of life and functioning impairment compared to control groups. By detecting neutrophilic granulocyte dysfunction in children with LCS, we shed light on a previously overlooked pathophysiological component of the condition. We demonstrate a significant correlation between clinical symptoms and superoxide production, further enhancing our understanding of the underlying mechanisms of pediatric LCS.

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