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 5

SARS-CoV-2 antibody response in children and young people with and without LC.

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SARS-CoV-2 antibody response in children and young people with and witho...
(A) Anti-RBD IgG antibody levels (P < 0.001) in responders in log (AU/mL). (B) Anti-S2 IgG antibody levels (P nonsignificant) in responders in log (AU/mL). (C) Anti-N IgG antibody levels (P nonsignificant) in responders in log (AU/mL). (D) Anti-RBD IgA antibody levels (P = 0.046) in responders in log (AU/mL). (E) Anti-S2 IgA antibody levels (P nonsignificant) in responders in log (AU/mL). (F) Anti-N IgA antibody levels (P nonsignificant) in responders in log (AU/mL). (G) SARS-CoV-2 neutralizing capacity (P = 0.048) of responders in log ID50 in the LC and control cohorts. (H) From left to right: correlation between neutralizing capacity (ID50) and anti-RBD IgG antibodies (AU/mL) (LC cohort, anti-RBD IgG/neutralizing capacity, P < 0.001, ρ = 0.73; control cohort, anti-RBD IgG/neutralizing capacity, P = 0.047, ρ = 0.57), correlation between neutralizing capacity (ID50) and anti-RBD IgA antibodies (AU/mL) (LC cohort, anti-RBD IgA/neutralizing capacity, P < 0.001, ρ = 0.58; control cohort, anti-RBD IgA/neutralizing capacity, P nonsignificant, ρ = –0.27) (I) From left to right: correlation between neutralizing capacity (ID50) and anti-S2 IgG antibodies (AU/mL) (LC cohort, anti-S2 IgG/neutralizing capacity, P < 0.001, ρ = 0.70; control cohort, anti-S2 IgG/neutralizing capacity, nonsignificant, ρ = 0.03), correlation between neutralizing capacity (ID50) and anti-S2 IgA antibodies (AU/mL) (LC cohort, anti-S2 IgA/neutralizing capacity, P < 0.001, ρ = 0.51; control cohort, anti-S2 IgA/neutralizing capacity, P nonsignificant, ρ = –0.40) in the LC and control cohorts. Antibody levels and neutralizing capacity were compared between the LC and control cohorts using linear regression models adjusted for SARS-CoV-2 antigen exposure, sex, and age as covariates. Each dot represents an individual, and median and IQR values are indicated. P values less than 0.05 were considered statistically significant.