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Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19
Krystallenia Paniskaki1,2, Sarah Goretzki1,3, Moritz Anft2
1Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Insights
Children with post-acute COVID-19 sequelae (PASC) show persistent SARS-CoV-2 specific T-cell responses, suggesting cellular inflammation may drive long COVID symptoms in pediatrics. Further research is needed for therapeutic strategies.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Viral Sequelae
Background:
- A subset of pediatric COVID-19 survivors experience persistent symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID.
- Clinical data and immune mechanisms underlying these pediatric post-acute COVID-19 sequelae (PASC) are not well understood.
Purpose of the Study:
- To comprehensively profile the clinical and immunological characteristics of children with PASC.
- To compare immune responses between children with and without PASC.
Main Methods:
- Clinical assessment including medical history, physical examination, and laboratory tests.
- Analysis of SARS-CoV-2 specific T-cell responses (CD4+ and CD8+) using multiparametric flow cytometry.
- Assessment of humoral immunity via pseudovirus neutralization and ELISA assays.
Main Results:
- Common PASC symptoms included shortness of breath, exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration.
- Elevated frequencies of SARS-CoV-2 spike (S) reactive CD4+ and CD8+ T cells with TNFα and IFNγ production and low functional avidity were observed in the PASC group.
- C-reactive protein (CRP) levels positively correlated with IFNγ-producing reactive CD8+ T cells.
Conclusions:
- Findings suggest a potential role for persistent SARS-CoV-2 triggered cellular inflammation in the development of pediatric PASC.
- These insights may inform future therapeutic and preventive strategies for long COVID in children.
Background:
A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce.
Methods:
In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay.
Results:
The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells.
Conclusions:
Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.
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