Salivary Biomarkers as Pioneering Indicators for Diagnosis and Severity Stratification of Pediatric Long COVID Provisionally Accepted

Sylwia D. Tyrkalska¹ Fernando Pérez-Sanz² Lorena Franco Martínez¹ Camila P. Rubio¹ Asta Tvarijonaviciute¹ Silvia Martínez-Subiela¹ María Méndez-Hernández³ Alba Gonzalez-Aumatell³ Clara Carreras-Abad³ Èlia Domènech-Marçal³ Jose Ceron¹ María L. Cayuela² Victoriano Mulero¹ Sergio Candel^1*

• ¹University of Murcia, Spain
• ²Murcia BioHealth Research Institute, University of Murcia, Spain
• ³Hospital Germans Trias i Pujol, Spain

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection.Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms post-acute infection. In this study, we examined 105 saliva samples (49 from children with long COVID and 56 controls), revealing significant alterations in salivary biomarkers. Pediatric long COVID exhibited increased oxidant biomarkers, decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms. This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unraveling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals.