Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC)
Krystallenia Paniskaki 1,2*+, Sarah Goretzki 1,3*, Moritz Anft 2, Margarethe J. Konik 1, Toni L. Meister4, Stephanie Pfaender 4, Klara Lechtenberg 3, Melanie Vogl 5, Burcin Dogan 3, Sebastian Dolff 1, Timm H. Westhoff 6, Hana Rohn 1, Ursula Felderhoff-Mueser 3,7, Ulrik Stervbo2, Oliver Witzke 1, Christian Dohna-Schwake 1,3,7 and Nina Babel2,8
1 Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
2 Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany
3 Department of Pediatrics I, University of Duisburg-Essen, Children´s Hospital Essen, Germany
4 Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
5 Department of Pediatrics III, Pediatric Pulmonology and Sleep Medicine, University of Duisburg-Essen, Children´s Hospital Essen, Germany
6 Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
7 Center for Translational Neuro- and Behavioral Sciences C-TNBS, University Duisburg-Essen, Essen, Germany
8 Berlin Institute of Health at Charité – University Clinic Berlin, BIH Center for Regenerative Therapies (BCRT) Berlin, Berlin, Germany
* equal contribution
+ Correspondence:
Dr. Krystallenia Paniskaki
email: kpaniskaki@gmail.com
Running title: Cellular inflammation in pediatric PASC
Word count: 2623
Tables: 2
Figures: 3
Competing Interests
All authors declare no competing interests.
Financial support
This work was supported by grants of Mercator Foundation, EFRE grant for COVID.DataNet. NRW, AiF grant for EpiCov, and BMBF for NoChro (FKZ 13GW0338B).
Abstract
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 flowcytometry 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.
Keywords: pediatric PASC, long COVID, T cells, neutralizing antibodies
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