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Pediatric long COVID is characterized by myeloid CCR6 suppression and immune dysregulation
Jon Izquierdo-Pujol, Núria Pedreño-López, Tetyana Pidkova, Maria Nevot, Victor Urrea, Fernando Laguía, Francisco Muñoz-López, Judith Dalmau, Alba Gonzalez-Aumatell, Clara Carreras-Abad, Maria Mendez, Carlos Rodrigo, Marta Massanella, Julià Blanco, Jorge Carrillo, Benjamin Trinité, Javier Martinez-Picado, Sara Morón-López
Jon Izquierdo-Pujol, Núria Pedreño-López, Tetyana Pidkova, Maria Nevot, Victor Urrea, Fernando Laguía, Francisco Muñoz-López, Judith Dalmau, Alba Gonzalez-Aumatell, Clara Carreras-Abad, Maria Mendez, Carlos Rodrigo, Marta Massanella, Julià Blanco, Jorge Carrillo, Benjamin Trinité, Javier Martinez-Picado, Sara Morón-López
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Research Article Clinical Research Immunology Infectious disease

Pediatric long COVID is characterized by myeloid CCR6 suppression and immune dysregulation

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Abstract

The biological mechanisms underlying long COVID in the pediatric population are poorly understood. Our study aimed to characterize the immune pathophysiology of long COVID in this population. We analyzed major immune cell compartments in PBMCs and the specific SARS-CoV-2 antibody response in 99 patients with long COVID and in 18 patients without long COVID at 3 months after acute infection. Our findings indicate that pediatric long COVID is associated with a dysregulated immune response characterized by altered innate immunity and overactivated T, B, and NK cell responses. Furthermore, young people with long COVID had an impaired humoral response to SARS-CoV-2 marked by a dysregulated B cell compartment and lower levels of anti-RBD IgG and IgA. This correlated with reduced neutralizing capacity against SARS-CoV-2. Random forest analysis identified CCR6 expression on myeloid cells as the most relevant biomarker that distinguishes individuals with long COVID from control individuals with 79% accuracy.

Authors

Jon Izquierdo-Pujol, Núria Pedreño-López, Tetyana Pidkova, Maria Nevot, Victor Urrea, Fernando Laguía, Francisco Muñoz-López, Judith Dalmau, Alba Gonzalez-Aumatell, Clara Carreras-Abad, Maria Mendez, Carlos Rodrigo, Marta Massanella, Julià Blanco, Jorge Carrillo, Benjamin Trinité, Javier Martinez-Picado, Sara Morón-López

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Figure 1

Myeloid cell compartment in children and young people with and without LC.

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Myeloid cell compartment in children and young people with and without L...
(A) Frequency of monocytes (P = 0.007, FDR = 0.007) and DCs (P = 0.004, FDR = 0.007) with respect to total myeloid cells among the LC and control cohorts. (B) Frequency of classical (P nonsignificant), intermediate (P nonsignificant), and nonclassical (P = 0.006, FDR = 0.030) monocytes with respect to total monocytes among the LC and control cohorts. (C) Frequency of pDCs (P = 0.043, FDR = 0.071), cDCs (P = 0.034, FDR = 0.071), and CD123– CD11c– DCs (P nonsignificant) with respect to total DCs in the LC and control cohorts. (D) Frequency of cluster 7 with respect to total cDCs among the LC and control cohorts (P = 0.002, FDR = 0.014). (E) Frequency of cluster 11 with respect to total classical monocytes in the LC and control cohorts (P< 0.001, FDR = 0.001). (F) MFI fold-change (FC) of CD169, CD38, CCR6, CCR7, CCR5, CXCR3, and CXCR5 in the LC and control cohorts in each of the myeloid cell populations. *P < 0.05, FDR < 0.05. The frequency of each cluster and the MFI of the different markers was compared between the LC and control cohorts using linear regression models adjusted for SARS-CoV-2 antigen exposure, sex, and age as covariates. In all analyses, LC group, n = 98; control group, n = 18. Each dot represents an individual, and median and IQR values are indicated. P values less than 0.05 were considered statistically significant and adjusted for multiple testing using FDR.

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