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

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 4

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

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B cell compartment in children and young people with and without LC. (A)...
(A) Frequency of major B cell populations with respect to total B cells among the LC and control cohorts (IgD-only B cells P = 0.004, FDR = 0.029; switched memory B cells P = 0.032, FDR = 0.110; other P = nonsignificant). (B) Frequency of switched memory (P = 0.032, FDR = 0.110) and IgD-only B cells (P = 0.004, FDR = 0.029) with respect to total B cells in the LC and control cohorts. (C) From left to right: frequency of cluster 15 (P = 0.006, FDR = 0.115) with respect to total switched memory B cells, frequency of cluster 23 (P = 0.033, FDR = 0.202) with respect to total MZ-like B cells, frequency of cluster 17 (P = 0.013, FDR = 0.127) with respect to total switched memory B cells, frequency of cluster 19 (P = 0.007, FDR = 0.115) with respect to total switched memory B cells, and frequency of cluster 25 (P = 0.021, FDR = 0.162) with respect to total MZ-like B cells in the LC and control cohorts. (D) MFI fold-change (FC) of CD127, CD1c, CD25, PD1, and CD95 between LC and control cohorts in each of the B 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 = 93; 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.