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Review
. 2021 Apr 29:9:629240.
doi: 10.3389/fped.2021.629240. eCollection 2021.

COVID-19 in Immunosuppressed Children

Affiliations
Review

COVID-19 in Immunosuppressed Children

Emanuele Nicastro et al. Front Pediatr. .

Abstract

Following the spread of the SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) to a global pandemic, concerns have arisen for the disease impact in at-risk populations, especially in immunocompromised hosts. On the other hand, clinical studies have clarified that the COVID-19 clinical burden is mostly due to over-inflammation and immune-mediated multiorgan injury. This has led to downsizing the role of immunosuppression as a determinant of outcome, and early reports confirm the hypothesis that patients undergoing immunosuppressive treatments do not have an increased risk of severe COVID-19 with respect to the general population. Intriguingly, SARS-CoV-2 natural reservoirs, such as bats and mice, have evolved mechanisms of tolerance involving selection of genes optimizing viral clearance through interferon type I and III responses and also dampening inflammasome response and cytokine expression. Children exhibit resistance to COVID-19 severe manifestations, and age-related features in innate and adaptive response possibly explaining this difference are discussed. A competent recognition by the innate immune system and controlled pro-inflammatory signaling seem to be the pillars of an effective response and the premise for pathogen clearance in SARS-CoV-2 infection. Immunosuppression-if not associated with other elements of fragility-do not represent per se an obstacle to this competent/tolerant phenotype in children. Several reports confirm that children receiving immunosuppressive medications have similar clinical involvement and outcomes as the pediatric general population, indicating that maintenance treatments should not be interrupted in suspect or confirmed SARS-CoV-2 infection.

Keywords: SARS–CoV−2; autoimmune disease; cancer; immunosuppression; innate immunity; kidney transplant; liver transplant; rheumatologic diseases.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of immune competence, tolerance, and immunopathology toward SARS-CoV-2 infection in different hosts and clinical scenarios. ADE, antibody-dependent enhancement; CNI, calcineurin inhibitors; CTL, cytotoxic T cell; CD71+ EC, CD71+ erythroid precursors; EC, lung epithelial cell; KD, Kawasaki disease; MDSC, myeloid-derived suppressor cells; Mϕ, macrophage; MIS-C, Multisystem Inflammatory Syndrome in Children; PRR, Pattern Recognition Receptor; TLR, Toll-like receptors.

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