Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children

Abstract

For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child’s daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host’s immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.

Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

“…Long COVID is still an unsolved puzzle for doctors and researchers, present in both children and adults [121]. The effects of SARS-CoV-2 infection, the molecular mechanisms involved in the modulation of intestinal permeability with an impact on autoimmunity [122], as well as the onset and persistence of LC symptoms are not yet fully elucidated, and multiorgan manifestations require multidisciplinary management.…”

“…The complex interplay between infection, dysbiosis, and inflammation at a molecular and cellular level could better guide scientists and physicians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection or LC [121].…”

“…The arrows indicate the closing of the dangerous circle that self-maintains and amplifies the inflammatory phenomena (Figure3was imagined and drawn by L.M.A. using Microsoft Paint 3D for Windows 10 and using completely free picture material from SeekPNG.com (accessed on 26 October 2023), for which we are very grateful), being modified after Figure 2[121]).…”