Background
Although most patients infected with SARS-CoV-2 recover, 10-20% can develop long-term persistent symptoms after the acute infection, a condition known as long COVID or Post-Acute Sequalae of SARS-CoV-2 (PASC). In this study we aim to compare autoantibodies, cytokines and neuronal and vascular damage biomarkers in plasma from children and young people (CYP) with and without PASC.
Methods
We analysed 130 EDTA plasma samples from the pediaCOVID cohort (Hospital Germans Trias i Pujol), which includes 108 CYP diagnosed with PASC and 22 controls (11 infected and 11 uninfected) at 3 months after acute infection. Autoantibodies against the M2 muscarinic and β2 adrenergic G-protein coupled receptors (GPCRs) and the vascular damage biomarkers endothelin-1, angiopoietin-2 and von Willebrand’s Factor were measured using ELISA; 42 inflammatory markers were measured by Luminex (HCYTOMAG-60K, Milliplex® Map Kit) and ELISA (Gal-9), and neuronal damage markers glial fibrillary acidic protein (GFAP) and neurofilaments (NfL) were measured by SIMOA® Technology.
Results
CYP with PASC had increased levels of autoantibodies against the β2 adrenergic receptor (p=0.007), a trend towards increased levels of autoantibodies against the M2 muscarinic receptor (p=0.065), and increased levels of the inflammatory markers eotaxin and PDGF-AB (p=0.018 and p=0.047 respectively) while showed decreased levels of RANTES (CCL5) (p=0.010) compared to the infected group. Moreover, CYP from the PASC and infected controls had higher levels of both GM-CSF and IL10 compared to the uninfected group (GM-CSF p=0.014, p=0.020; IL10 p=0.021, p=0.037 respectively). Finally, there were no significant differences in both vascular and neuronal damage biomarkers between CYP with and without PASC.
Conclusions
These results demonstrates that CYP with PASC have inflammatory dysregulation and increased levels of autoantibodies, suggesting a potential role of the immune system in pediatric PASC. Interestingly, the β2 muscarinic GPCRs autoantibodies has already been shown to be increased in adults with PASC, suggesting a common link between pediatric and adult PASC physiopathology not shown before. Moreover, our results on vascular and neuronal damage biomarkers suggests that CYP with PASC had no vascular nor neuronal damage at 3 months after the acute infection. More comprehensive studies must be done to decipher if this immune dysregulation is a consequence or a cause of PASC.