Coronavirus disease 2019 (COVID‐19), can present with a wide spectrum of severity. Elderly patients with cardiac, pulmonary and metabolic comorbidities are more likely to develop the severe manifestations of COVID‐19, which are observed in less than 5% of the pediatric patients. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is able to induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators, strongly contributing to the pulmonary and systemic manifestations in COVID‐19. In children, the immune dysregulation following SARS‐CoV‐2 can also be responsible of a severe disease phenotype defined as multisystem inflammatory syndrome in children. As the immune system undergoes a complex process of maturation from birth to adult age, differences in the immune and inflammatory response could have a significant impact in determining the spectrum of severity of COVID‐19. Indeed, children show a higher ability to respond to viral infections and a reduced baseline pro‐inflammatory state compared with elderly patients. Age and comorbidities contribute to disease severity through immune‐mediated mechanisms, since they are associated with a chronic increase of pro‐inflammatory mediators, and cause an enhanced susceptibility to develop an immune dysregulation following SARS‐CoV‐2 infection. Also the expression of ACE2, the receptor of SARS‐CoV‐2, varies with age, and is linked to the immune and inflammatory response through a complex, and not completely elucidated, network. This paper reviews the peculiar immunopathogenic aspects of COVID‐19, with a focus on the differences between adult and pediatric patients.

The influence of the central nervous system and autonomic system on cardiac activity is being intensively studied, as it contributes to the high rate of cardiologic comorbidities observed in people with epilepsy. Indeed, neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation, have been shown to produce arrhythmia both experimentally and clinically. Moreover, seizures may induce a variety of transient cardiac effects, which include changes in heart rate, heart rate variability, arrhythmias, asystole, and other ECG abnormalities, and can trigger the development of Takotsubo syndrome. People with epilepsy are at a higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Although the cause of SUDEP is still unknown, cardiac abnormalities during and between seizures could play a significant role in its pathogenesis, as highlighted by studies on animal models of SUDEP and registration of SUDEP events. Recently, genetic mutations in genes co-expressed in the heart and brain, which may result in epilepsy and cardiac comorbidity/increased risk for SUDEP, have been described. Recognition and a better understanding of brainheart interactions, together with new advances in sequencing techniques, may provide new insights into future novel therapies and help in the prevention of cardiac dysfunction and sudden death in epileptic individuals.

Over the last two decades, the prevalence of food allergies has registered a significant increase in Westernized societies, potentially due to changes in environmental exposure and lifestyle. The pathogenesis of food allergies is complex and includes genetic, epigenetic and environmental factors. New evidence has highlighted the role of the intestinal microbiome in the maintenance of the immune tolerance to foods and the potential pathogenic role of early percutaneous exposure to allergens. The recent increase in food allergy rates has led to a reconsideration of prevention strategies for atopic diseases, mainly targeting the timing of the introduction of solid foods into infants’ diet. Early recommendation for high atopy risk infants to delay the introduction of potential food allergens, such as cow’s milk, egg, and peanut, until after the first year of life, has been rescinded, as emerging evidence has shown that these approaches are not effective in preventing food allergies. More recently, high-quality clinical trials have suggested an opposite approach, which promotes early introduction of potential food allergens into infants’ diet as a means to prevent food allergies. This evidence has led to the production of new guidelines recommending early introduction of peanut as a preventive strategy for peanut allergy. However, clinical trials investigating whether this preventive dietary approach could also apply to other types of food allergens have reported ambiguous results. This review focuses on the latest high-quality evidence from randomized controlled clinical trials examining the timing of solid food introduction as a strategy to prevent food allergies and also discusses the possible implications of early complementary feeding on both the benefits and the total duration of breastfeeding.

Background The role of the immune system and inflammatory response in the pathogenesis of the severe manifestations of coronavirus disease 2019 (COVID-19) is well known. Currently, different therapies active on the immune system are used for the management of COVID-19. The involvement of the immune system also opens the opportunity for the use of nutritional supplements with antimicrobial and immunomodulatory activity. Main aspects Nutritional supplements with antimicrobial and immunomodulatory activity are promising therapeutic adjuvants for the treatment of COVID-19, and also for the prevention of viral spreading. In particular, the role of vitamin D, probiotics, lactoferrin, and zinc is of significant clinical interest, although there are only a few data on their use in COVID-19 patients. Their molecular actions, together with the results of studies performed on other respiratory infections, strongly suggest their potential utility in COVID-19. This article discusses the main properties of these nutritional supplements and their potential applicability in the prevention and treatment of COVID-19. Conclusion The supplementation with vitamin D, probiotics, lactoferrin and zinc could have a role both in preventing SARS-CoV-2 infection and in mitigating the clinical course in infected patients, contributing in the prevention of immune-mediated organ damage.

During the last years, studies investigating the intriguing association between immunodeficiency and autoimmunity led to the discovery of new monogenic disorders, the improvement in the knowledge of the pathogenesis of autoimmunity, and the introduction of targeted treatments. Autoimmunity is observed with particular frequency in patients with primary antibody deficiencies, such as common variable immunodeficiency (CVID) and selective IgA deficiency, but combined immunodeficiency disorders (CIDs) and disorders of innate immunity have also been associated with autoimmunity. Among CIDs, the highest incidence of autoimmunity is described in patients with autoimmune polyendocrine syndrome 1, LRBA, and CTLA-4 deficiency, and in patients with STAT-related disorders. The pathogenesis of autoimmunity in patients with immunodeficiency is far to be fully elucidated. However, altered germ center reactions, impaired central and peripheral lymphocyte negative selection, uncontrolled lymphocyte proliferation, ineffective cytoskeletal function, innate immune defects, and defective clearance of the infectious agents play an important role. In this paper, we review the main immunodeficiencies associated with autoimmunity, focusing on the pathogenic mechanisms responsible for autoimmunity in each condition and on the therapeutic strategies. Moreover, we provide a diagnostic algorithm for the diagnosis of PIDs in patients with autoimmunity.