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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