Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era.

Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset-such as non-remitting high fever, headache, rash, or arthralgia-and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care-a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS-so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.

Light as a Cure in COVID-19: A Challenge for Medicine

Light and lasers, as high-tech devices whose medical potential has yet to be fully discovered, have made important contributions to medicine, even in the current pandemic. The main aim of this review was to investigate how light was applied as a therapeutic tool during a crisis triggered by COVID-19. Another goal was to encourage scientists and industry to quickly design new at-home photobiomodulation therapy (PBMT) and/or antimicrobial photodynamic therapy (aPDT) easy to use systems to end this pandemic, especially for those who believe in high-tech but would never get vaccinated. This review revealed that PBMT has been successfully applied as adjunct therapy, in combination with conventional medical treatment, and as a pioneering action in SARS-CoV-2 infection, demonstrating significant improvements in airway inflammation and general clinical condition of patients, a faster recovery, avoiding intensive care unit (ICU) hospitalization, mechanical ventilation, mortality, and overcoming long-term sequelae. Application in only a limited number of cases strongly suggests the need for future randomized, placebo-controlled clinical trials to objectively determine the action and effects of PBMT in COVID-19. Implementation of unparalleled theragnostics methods and light-based techniques for disinfection of spaces, air, skin, mucosae, and textures to decrease the load of SARS-CoV-2 virus would save lives, time, and money. In this ongoing and challenging search for the seemingly intangible end of this pandemic, a non-invasive, easily accessible, safe, and side-effect-free adjuvant method appears to be PBMT, alone or in synergistic combination with aPDT, which has been shown to work in COVID-19 and opens unprecedented potential for use as home self-treatment to end the pandemic.

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic.

Celiac disease (CD) comprises over 1% of the world's population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.

Implications of SARS-CoV-2 Infection in Systemic Juvenile Idiopathic Arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is a serious multifactorial autoinflammatory disease with a significant mortality rate due to macrophage activation syndrome (MAS). Recent research has deepened the knowledge about the pathophysiological mechanisms of sJIA-MAS, facilitating new targeted treatments, and biological disease-modifying antirheumatic drugs (bDMARDs), which significantly changed the course of the disease and prognosis. This review highlights that children are less likely to suffer severe COVID-19 infection, but at approximately 2-4 weeks, some cases of multisystem inflammatory syndrome in children (MIS-C) have been reported, with a fulminant course. Previous established treatments for cytokine storm syndrome (CSS) have guided COVID-19 therapeutics. sJIA-MAS is different from severe cases of COVID-19, a unique immune process in which a huge release of cytokines will especially flood the lungs. In this context, MIS-C should be reinterpreted as a special MAS, and long-term protection against SARS-CoV-2 infection can only be provided by the vaccine, but we do not yet have sufficient data. COVID-19 does not appear to have a substantial impact on rheumatic and musculoskeletal diseases (RMDs) activity in children treated with bDMARDs, but the clinical features, severity and outcome in these patients under various drugs are not yet easy to predict. Multicenter randomized controlled trials are still needed to determine when and by what means immunoregulatory products should be administered to patients with sJIA-MAS with a negative corticosteroid response or contraindications, to optimize their health and safety in the COVID era.