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Giulia Brindisi,1,* Valentina De Vittori,1,* Rosalba De Nola,2,3 Antonio Di Mauro,4 Giovanna De Castro,1 Maria Elisabetta Baldassarre,4 Ettore Cicinelli,2 Bianca Cinicola,1 Marzia Duse,1 Anna Maria Zicari1 1Pediatrics Department, Umberto I Hospital, Sapienza University, Rome, 00161, Italy; 2Department of Biomedical Science and Human Oncology, Gynecology and Obstetrics Section, “Aldo Moro” University of Bari, Bari, 70124, Italy; 3Department of Tissues and Organs Transplantation and Cellular Therapies, “Aldo Moro” University of Bari, Bari, 70124, Italy; 4Department of Biomedical Sciences and Human Oncology-Neonatology and Neonatal Intensive Care Unit, “Aldo Moro” University of Bari, Bari, 70124, Italy*These authors contributed equally to this workCorrespondence: Giulia BrindisiPediatrics Department, Umberto I Hospital, Sapienza University, Viale Regina Elena 324, Rome, 00161, ItalyTel +39 06 49979333Email giulia.brindisi@gmail.comBackground: Allergic rhinitis (AR) and asthma are two common atopic diseases, often associated with a common ethiopathogenesis characterized by a Th2 inflammatory response with the release of many biomarkers, such as nitric oxide (NO).Purpose: To evaluate and compare inflammatory (nFeNO and eFeNO) and functional (mNF and FEV1) parameters in AR children with or without asthma in comparison to controls. Secondly, we aimed to identify nFeNO cut-off values and verify their reliability to predict the presence of rhinitis or asthma alone or in combination.Patients and Methods: We enrolled 160 children (6– 12 years of age) with AR and/or asthma divided into four groups: controls, AR, asthma, and AR + asthma. All children underwent the following inflammatory and functional measurements: nFeNO, eFeNO, mNF and FEV1.Results: We observed that levels of nFeNO were extremely higher in children with AR and even more in those with AR + asthma in respect to controls. Notably, all the pathological conditions, especially AR + asthma, showed significantly lower values of mNF compared to healthy children. A negative correlation linked mNF and nFeNO. Then, we found eFeNO values significantly higher in all the pathological groups compared to controls, with major values of this marker in patients affected by asthma and AR + asthma, as well as FEV1 values significantly lower in all the disease groups, especially in children with asthma and AR+ asthma. ROC curve analysis showed that nFeNO was a great predictor for rhinitis alone or with asthma, revealing an accurate cut-off of 662 ppb.Conclusion: nFeNO measurement is non-invasive, easy to perform, economic and a valuable test in case of AR alone or in association with asthma. Thus, it should be used in patients with rhinitis, together with anterior active rhinomanometry (AAR) to diagnose and estimate the degree of nasal obstruction but also in children with asthma to assess their nasal involvement and improve the therapeutic management.Keywords: nasal nitric oxide, exhaled nitric oxide, anterior active rhinomanometry, allergic rhinitis, asthma, children

Background: Subjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but the mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play a role in this process, leading to endothelial dysfunction and an increased susceptibility to thrombosis. The purpose of this study was to assess the redox state in individuals with ATM mutations and determine its impact on endothelial function., Methods: In this cross-sectional study, twenty-seven children with ataxia telangiectasia (AT) (13 males and 14 females, mean age 15.1 ± 7.6 years) were compared with 27 controls (13 males and 14 females, mean age 14.6 ± 8.4 years) matched for age and gender. Additionally, 29 AT parents with heterozygous mutation of ATM (h-ATM) gene, and 29 age- and gender-matched controls were included. Endothelial function was evaluated through brachial flow-mediated dilation (FMD) and the assessment of nitric oxide (NO) bioavailability. Oxidative stress was evaluated by measuring serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H 2 O 2 ) production, and hydrogen breakdown activity (HBA). Thrombus formation was assessed through the Total Thrombus Formation Analysis System (T-TAS)., Results: AT children and parents with heterozygous ATM mutations exhibited significantly lower FMD, HBA, and NO bioavailability as compared to age and gender matched controls. AT children and ATM carrier of heterozygous ATM mutations had significantly higher concentrations of sNOX2-dp and H 2 O 2 as compared to controls. Compared to the respective controls, AT children and their parents, who carried heterozygous ATM mutation, showed an accelerated thrombus growth as revealed by reduced occlusion time. Multivariable linear regression analysis revealed that sNOX2 (standardized coefficient β: -0.296; SE: 0.044; p = 0.002) and NO bioavailability (standardized coefficient β: 0.224; SE: 0.065; p = 0.02) emerged as the only independent predictive variables associated with FMD (R 2 : 0.44)., Conclusions: This study demonstrates that individuals with ATM mutations experience endothelial dysfunction, increased oxidative stress, and elevated thrombus formation. These factors collectively contribute to the heightened susceptibility of these individuals to develop atherosclerosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease that affects both eyes, often with asymmetric severity, potentially causing major visual complications. The seasonal management of VKC can be challenging, especially when specialists with different diagnostic and therapeutic approaches need to be consulted. The aim of this expert panel was to reach a national consensus among pediatric allergologists and ophthalmologists on the diagnosis and treatment of VKC. This consensus was developed by an expert panel of 17 Italian pediatric allergologists and ophthalmologists with over a decade of experience. Ten statements on VKC diagnosis and treatment formulated after a thorough review of current literature were evaluated by the panelists. The level of agreement was quantitatively assessed using a 5-point Likert scale. Consensus was reached if ≥ 75.0% of panelists agreed to any given statement. The consensus emphasizes the importance of evaluation by multispecialty reference centers or experienced specialists for accurate diagnosis. Prompt diagnosis, especially during active phases, is crucial and should occur before corticosteroid therapy. The Bonini score from 2007 is the preferred tool for VKC assessment, although future revisions may be considered. Short cycles of topical corticosteroids should be preferred over prolonged use, even during immunomodulatory therapy. When cyclosporine fails, tacrolimus should be considered., Conclusion: This is the first consensus on the management of VKC that has gathered the expert opinions of both pediatricians and ophthalmologists. The outcome of this multidisciplinary effort provides a uniform approach to VKC diagnosis and treatment, thereby facilitating patient management across the country., What Is Known: • Vernal keratoconjunctivitis (VKC) is a chronic recurrent ocular disease particularly prevalent in the pediatric population. • Despite its relevance, there is a lack of standardized approaches shared between pediatricians and ophthalmologists, leading to notable variations in clinical practice., What Is New: • This expert panel, comprising 17 pediatric allergologists and ophthalmologists, has reached a national consensus to provide standardized guidance for VKC management. • The consensus emphasizes the importance of a multidisciplinary approach to managing VKC, ensuring consistent and effective patient care., (© 2024. The Author(s).)

Summary: Background. Allergic rhinitis (AR) is a widespread condition. The Italian Society of Pediatric Allergology and Immunology (SIAIP) promoted an initiative to update the knowledge on AR in children and adolescents. The present survey directly addressed primary care pediatricians, thus reflecting the real-world management of AR in children and adolescents. The aim was to investigate common practice in managing AR children. Methods. A panel of experts drafted a series of questions concerning the practical management of children with AR in clinical practice. The questionnaire was administered to a large sample of primary care pediatricians (864). Results. 864 primary care pediatricians participated to the survey. Each pediatrician on average follows 94 children with AR; globally 81,231 children. More than 70% of participants follow ARIA guidelines. Accordingly, 42% of children have mild AR and 58% moderate/severe. Asthma, conjunctivitis and adenoid hypertrophy are the most common comorbidity. Most pediatricians autonomously follow their patients. The intensity of treatment (use of medication) is directly proportional to the symptom severity.  Intranasal corticosteroids are the most common medication used followed by oral antihistamines and nasal lavages (with hypertonic or isotonic solution). Up to 20% of participants prescribe the fixed association topical corticosteroids plus antihistamine. Conclusions . The present survey demonstrated that Italian primary care pediatricians accomplish ARIA guidelines and adapt treatment on the basis of the intensity of symptoms. Corticosteroids and antihistamines are the most common prescribed medications. Nasal lavages are also popular.

Background: Seasonal allergic rhinoconjunctivitis (SAR) is a worldwide health problem, especially in Westernized countries. Previous studies of the "Panallergens in Pediatrics" (PAN-PED) cohort found that molecular spreading (ie, the progressive increase in serum specific IgE antibody levels) of the IgE response to the grass pollen, Phleum pratense , molecules is directly associated with polysensitization to pollen in general.The research question is aimed at verifying whether this association can also be detected for non-pollen allergens, specifically Dermatophagoides pteronyssinnus ( D.pt ), to better understand the relationship between a perennial allergen ( D.pt ) and a seasonal allergen ( Phleum pratense ).To this end, our first objective was to analyze the biobank of the PAN-PED cohort serum by measuring the IgE levels to D.pt and its major recombinant molecules (Der p1, Der p2, Der p23); subsequently we investigated their correlation towards Phleum pratense IgE response, studying also the relationship between the molecular spreading of these 2 different allergens., Methods: Among 1120 patients positive to Phleum pratense , 638 were also sensitized to D.pt . Patients underwent skin prick tests (SPT) for inhalant extracts, and their serum was tested for total IgE (tIgE), and sIgE to pollen and perennial allergens. Considering the molecular allergen detection through the component resolved diagnosis (CRD), out of 638 patients, 146 were further investigated by performing IgE tests of the 3 major D.pt. molecules: Der p1, Der p2, and Der p23., Results: We found that a broader molecular response to Phleum pratense molecules, assessed by CRD, was associated with higher tIgE levels, polysensitization to pollens, and higher IgE levels to pollens, but also to lower IgE levels to D.pt and lower degree of sensitization to rDer p1, r Der p2, and rDer p23. In a multivariate linear model, the number of Phleum pratense molecules recognized by IgE was still inversely associated with the IgE level to D.pt extract., Conclusions: The main finding of this study was the detection of an inverse association, never described in the literature, between the molecular spreading of the IgE response to Phleum pratense and the IgE response to D.pt . This led us to speculate on the etiopathogenetic hypothesis according to which, among the majority of pollen allergic patients, a strong and molecularly diversified IgE response may be limited to pollen allergens and may be preventing or contrasting the development of an equally strong and diversified IgE sensitization to D.pt molecules. The biological mechanisms underlying this phenomenon deserve to be investigated., Competing Interests: Dr. P. Matricardi reports grants and personal fees from Euroimmun AG; grants and personal fees from Thermo Fisher Scientific, personal fees from Hycor Biomedical Inc, outside the submitted work. Dr S. Tripodi is cofounder of TPS Production. All other authors declared no conflicts of interest., (© 2024 The Authors.)

Food allergy (FA) affects approximately 6-8% of young children, with a peak prevalence at approximately one year of age. Tree nut and peanut allergies are among the main causes of anaphylaxis in the world. The gold standard for the diagnosis of FAs is the oral food challenge (OFC). Other diagnostic tests used in the clinical practice are skin prick tests (SPTs) and laboratory tests to measure out the presence of serum specific IgE (sIgE). In this narrative review, we collect the current evidence of the predictive value (PV) of SPTs and sIgE for the outcome of the OFCs. In literature, data are conflicting as to whether increasing sIgE concentration and wheal size in SPTs correlate with OFC outcomes. Most studies included in our review have shown that in vivo and in vitro tests may predict OFC outcomes with variable PV, but data are not conclusive; therefore, the OFC currently remains the gold standard for FA diagnosis.

Background: Despite the worldwide increasing incidence of Group A Streptococcus (GAS) infections reported since December 2022, data on noninvasive GAS (nGAS) infections in the post COVID-19 era are limited. By a self-reported survey performed in an outpatient setting, we investigated the number and clinical features of GAS infections, the diagnostic work-up and the type of treatment utilized. In addition, the rate of influenza vaccination was evaluated., Methods: In June 2023 family pediatricians involved in the study sent the survey to parents of patients aged 0-16 years. The survey included questions on GAS infections that occurred from January 1 to May 31, 2023., Results: Among 3580 children, 20.3% had a GAS infection (0,8% < 1 year, 16,4% 1-3 years, 42,3% 3-6 years, 26,5% 6-9 years, 11,4%, 9-12 years, and 2,6% 12-16 years). Symptoms reported were sore throat (76.9%), fever (75.2%), tonsillar exudate (25.2%), lymphadenopathy (21.8%), and scarlet fever (14.7%). A single patient was hospitalized due to GAS meningitis. Twenty four percent of children had more than one GAS infection. In this group, frequencies of symptoms reported in the first and in the following infection were similar, except for fever and scarlet fever which were less frequent during relapses. GAS was identified by rapid antigen detection test in 81.0% of children. Eighty-nine per cent of children were treated with antibiotics, mostly amoxicillin/clavulanate (40.4%) and amoxicillin (39.4%). Thirty four percent of children received influenza vaccine. No difference was observed among immunized and not immunized regarding the number and characteristics of GAS infection., Conclusions: We reported a certain prevalence of nGAS infections in children, mainly those aged 3-6 years age, who were mostly characterized by a low score of symptoms, and in most of the cases diagnosed and treated using a microbiological test as confirmatory tool. In this new clinical setting, a national study would be useful to reach more significant data for the definition of a correct diagnosis and clinical management of nGAS infections in children. Moreover, it is important to improve flu vaccination campaign and coverage to protect children from coinfections that could worsen the disease and misdiagnose the etiology of pharyngitis., (© 2024. The Author(s).)

Recent progress in the methods of genetic diagnosis of inborn errors of immunity has contributed to a better understanding of the pathogenesis of chronic mucocutaneous candidiasis (CMC) and potential therapeutic options. This review describes the latest advances in the understanding of the pathophysiology, diagnostic strategies, and management of chronic mucocutaneous candidiasis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Food supplements are defined as foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, often referred to as nutraceuticals, may exert benefit to the human body. Their use is increasing worldwide, including Europe and in Italy. However, some doctors are skeptical about their effectiveness and safety. This reluctance may depend on poor knowledge of the mechanisms of action and clinical evidence in literature. The Italian Society of Pediatric Allergy and Immunology (SIAIP) promoted the institution of an ad hoc Committee. The first initiative performed by this Committee was the administration of a questionnaire to the members of SIAIP.The results of this survey provided interesting results. Most pediatricians know the food supplement concept but frequently need help understanding the mechanisms of action. Most prescribe food supplements, mainly for preventing infections or enhancing immune defense. In addition, they prefer to use food supplements as cycles or add-on therapy. Finally, most participants like to attend events on this issue and contribute to new evidence through trials.In conclusion, this survey underscores the relevance of food supplement issues and attests to interest in this topic. However, there is a need to provide information and promote studies on this matter., (© 2024. The Author(s).)

The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin's multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.

Background: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice., Objective: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities., Methods: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7., Results: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%)., Conclusions: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4 + T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4 + T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H 2 O 2 ) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H 2 O 2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lorenzo Loffredo reports financial support was provided by University of Rome La Sapienza. Lorenzo Loffredo reports a relationship with University of Rome La Sapienza that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood., Methods: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA)., Results: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period., Conclusions: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Food allergy (FA) affects approximately 6-8% of children worldwide causing a significant impact on the quality of life of children and their families. In past years, the possible role of weaning in the development of FA has been studied. According to recent studies, this is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collect the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food. As shown in most of the studies included in this review, early food introduction did not show a potential protective role against FA development, and we conclude that further evidence is needed from future clinical trials.

This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A β-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology., Competing Interests: 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., (© 2024 Leonardi, Lorenzetti, Carsetti, Piano Mortari, Guido, Zicari, Förster-Waldl, Loffredo, Duse and Spalice.)

We carefully read the correspondence [...].

Children with SARS-CoV-2 are mostly mild symptomatic, but they may develop conditions, such as persisting symptoms, that may put them at greater risk of complications. Our aim was to evaluate the frequency and the presence of risk factors for persisting COVID-19 symptoms in children. We carried out a prospective observational study of the clinical manifestation of Long COVID at the Department of Maternal Infantile Science of a tertiary University hospital in Rome. We included 697 children (0-18 years), with previous SARS-CoV-2 infection. Children and parents were asked questions regarding persistent symptoms of COVID-19. Children with symptoms 30 days after initial diagnosis were 185/697 (26.4%). Moreover, 81/697 (11.6%) patients presented symptoms 90 days after the diagnosis. Thirty-day-persisting symptoms were mostly present in children with anosmia, atopy, asthenia, and cough in the acute phase compared with the asymptomatic children 30 days after infection. After 90 days, symptoms described were mainly neurological (47/697 children, 6.7%), and headache (19/697; 2.7%) was the most frequent manifestation. In conclusion, a relatively large proportion of the patients reported persisting symptoms that seem to be related to the symptom burden and to the atopy. Ninety days after the infection, most of the children had recovered, showing that long-term effects are not frequent. Limitations of the study include the single-center design and the lack of a control group.

Kiwifruit allergy is an emerging pathological condition in both general and pediatric populations with a wide range of symptoms linked to variable molecular patterns, justifying systemic and cross-reactions with other allergens (i.e., latex, pollen, and fruit). Skin prick test (SPT), specific serum IgE (Act d 1, Act d 2, Act d 5, Act d 8, and Act d 10) directed against five out of thirteen molecular allergens described in the literature, and oral test challenge with kiwifruit are available for defining diagnosis. The management is similar to that of other food allergies, mostly based on an elimination diet. Although kiwi allergy has been on the rise in recent years, few studies have evaluated the clinical characteristics and methods of investigating this form of allergy. Data collected so far show severe allergic reaction to be more frequent in children compared to adults. Therefore, the aim of this review is to collect the reported clinical features and the available association with specific molecular patterns of recognition to better understand how to manage these patients and improve daily clinical practice.

Background: We followed the effects of a new SCIT with a chemically polymerized allergen Alt a1, evaluating the trend of clinical and functional parameters in an observational-prospective study., Methods: 42 children with AR and intermittent asthma sensitized to A.A.: 17 patients started SCIT (Modigoid ® ), and 25 continued symptomatic therapy. At the initial visit (T0), all patients performed total IgE (tIgE) and specific IgE (sIgE) for Alt a1, nasal nitric oxide (nFeNo), nasal cytology, anterior active rhinomanometry (AAR) and spirometry. After 24 months (T1), they repeated the same procedures as in T0., Results: Patients treated with Modigoid presented a statistically significant ( p < 0.001) reduction of nFeNO (T0:1651.06 ± 149.18; T1: 1394.12 ± 108.98), tIgE (T0: 311.48 ± 144.18; T1: 164.73 ± 50.69), sIgE for Alt a1 (T0: 28.59 ± 12.69; T1: 19.54 ± 7.37), an improvement of nasal airflow (T0: 71.62 ± 8.66; T1: 95.12 ± 5.91), nasal eosinophils (T0: 20.59 ± 2.35; T1: 14.88 ± 1.65) and FEV1 (T0: 95.58 ± 7.91; T1: 116.64 ± 5.94)., Conclusions: The new SCIT for Alt a1 significantly improves AR symptoms from a subjective, objective point of view and laboratory and functional parameters.

Cow's milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or "dysbiosis". Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics' efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms.

Background and aims : Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H 2 O 2 ) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H 2 O 2 , TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H 2 O 2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

PaO 2 /FiO 2 (P/F ratio) is considered a marker of hypoxia/hypoxemia and mortality. Several prothrombotic changes are associated with the decrease of P/F ratio. The role of P/F ratio in patients with arterial and venous thrombosis remains unclear. The aim of this study was to assess in patients with coronavirus disease 2019 (COVID-19), the association between P/F ratio and arterial/venous thrombosis. One thousand and four hundred and six COVID-19 patients were recruited; 289 (21%) patients had P/F ratio < 200 and 1117 (79%) ≥ 200. Compared to the patients with P/F ratio ≥ 200, those with P/F ratio < 200 were older and with higher levels of glycemia, D-dimer and lower levels of albumin. Multiple linear regression analysis showed that albumin (standardized coefficient β:  0.156; SE: 0.001; p = 0.0001) and D-dimer (standardized coefficient β: -0.135; SE: 0.0001; p = 0.0001) were associated with P/F ratio. During the hospitalization 159 patients were transferred in intensive care unit (ICU), 253 patients died, 156 patients had arterial or venous thrombotic events. A bivariate logistic analysis was performed to analyze the predictors of thrombosis in COVID-19 patients; P/F ratio < 200 (Odds Ratio: [OR] 1.718, 95% Confidence Interval [CI] 1.085-2.718, p = 0.021), albumin (OR 1.693, 95% CI 1.055-2.716, p = 0.029), D-dimer (OR 3.469, 95% CI 2.110-5.703, p < 0.0001), coronary artery disease (CAD) (OR 1.800, 95% CI 1.086-2.984, p = 0.023) and heart failure (OR 2.410 95% CI 1.385-4.193, p = 0.002) independently predicted thrombotic events in this population. This study suggests that the P/F ratio is associated with thrombotic events by promoting a hypercoagulation state in patients hospitalized for COVID-19., (© 2023. The Author(s).)

Background: The aim of this study was to test whether rapid palatal expansion is effective to improve nasal airway patency in a sample of pediatric patients with primary snoring., Methods: A group of 21 subjects, 11 girls (52%) and 10 boys (48%), with a mean age of 7.1 years (SD=1.3; range 4-9 years) were treated with a rapid maxillary expansion (RME) device. Nasal airway resistance was assessed via rhinomanometric exam before (pre-) and 6 months after (post-) the rapid palatal expansion treatment., Results: Data analysis showed a statistically significant increase in the mean scores of the results of the rhinomanometric exam between the pre- and post-measurements with a significant reduction in total inspiratory and expiratory air resistance values after rapid palatal expansion., Conclusions: Our results show that RME treatment is associated with an improvement in nasal airway resistance due to a substantial reduction in nasal resistance associated with the orthopedic action of the orthodontic device.

SARS-CoV-2 mRNA vaccines prevent severe COVID-19 by generating immune memory, comprising specific antibodies and memory B and T cells. Although children are at low risk of severe COVID-19, the spreading of highly transmissible variants has led to increasing in COVID-19 cases and hospitalizations also in the youngest, but vaccine coverage remains low. Immunogenicity to mRNA vaccines has not been extensively studied in children 5 to 11 years old. In particular, cellular immunity to the wild-type strain (Wuhan) and the cross-reactive response to the Omicron variant of concern has not been investigated. We assessed the humoral and cellular immune response to the SARS-CoV-2 BNT162b2 vaccine in 27 healthy children. We demonstrated that vaccination induced a potent humoral and cellular immune response in all vaccinees. By using spike-specific memory B cells as a measurable imprint of a previous infection, we found that 50% of the children had signs of a past, undiagnosed infection before vaccination. Children with pre-existent immune memory generated significantly increased levels of specific antibodies, and memory T and B cells, directed against not only the wild type virus but also the omicron variant., Competing Interests: 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., (Copyright © 2022 Cinicola, Piano Mortari, Zicari, Agrati, Bordoni, Albano, Fedele, Schiavoni, Leone, Fiore, Capponi, Conti, Petrarca, Stefanelli, Spalice, Midulla, Palamara, Quinti, Locatelli and Carsetti.)

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment.

Background: Selective IgA deficiency (SIgAD) is the most common inborn error of immunity. The exact prevalence and pathogenesis of allergy in SIgAD have not yet been defined. We aimed to describe the prevalence and the characteristics of allergy in pediatric SIgAD subjects, evaluate the association between allergy and other comorbidities, and define the immune phenotype of allergic and non-allergic patients., Methods: Clinical and immunological data from 67 SIgAD patients were collected over a 13-year period at a single center. Patients' characteristics were analyzed according to the presence of allergy., Results: Allergy was diagnosed in 34% of SIgAD patients, with a median age at allergy diagnosis of 8 years. Allergy was the second-most-common clinical manifestation, following recurrent respiratory infections. Among the allergic group, 74% had rhinitis, 30% asthma, 30% atopic dermatitis, and 22% food allergy; one out of three had more than one allergic manifestation. SIgAD patients showed more frequent transitory lymphopenia and a lower count of CD19+ at diagnosis than at last FU. However, compared to non-allergic subjects, allergic patients did not differ in their immune phenotype, number and severity of infections, or increased autoimmunity., Conclusions: In our longitudinal study, compared to non-allergic SIgAD patients, those with allergies did not present a more severe immune defect or complex clinical phenotype. However, evaluation and early identification of allergy in the context of SIgAD assessment, both at diagnosis and during FU, and definition of a proper management are important to prevent complications and improve the patient's quality of life.

During the COVID-19 pandemic, lung ultrasound (LUS) was widely used to assess SARS-CoV-2 infection. To date, there are patients with persistence of symptoms after acute infection. Therefore, it may be useful to have an objective tool to follow these patients. The aim of our study was to evaluate the presence of LUS artifacts after SARS-CoV-2 infection in children and to analyze the associations between time elapsed since infection and symptomatology during acute infection. We conducted an observational study, enrolling 607 children infected with SARS-CoV-2 in the previous twelve months. All patients performed a LUS and medical history of demographic and clinical data. We observed irregular pleural lines in 27.5%, B-lines in 16.9%, and subpleural consolidations in 8.6% of the cases. These artifacts were more frequently observed in the lower lobe projections. We have observed that the frequency of artifacts decreases with increasing time since infection. In symptomatic patients during COVID infection, B-lines ( p = 0.02) were more frequently found. In our sample, some children, even after months of acute infection, have ultrasound artifacts and showed an improvement with the passage of time from the acute episode. Our study provides additional evidence about LUS in children with previous COVID-19 as a support to follow these patients in the months following the infection.

Starting from the "Hygiene Hypothesis" to the "Microflora hypothesis" we provided an overview of the symbiotic and dynamic equilibrium between microbiota and the immune system, focusing on the role of dysbiosis in atopic march, particularly on allergic rhinitis. The advent of deep sequencing technologies and metabolomics allowed us to better characterize the microbiota diversity between individuals and body sites. Each body site, with its own specific environmental niches, shapes the microbiota conditioning colonization and its metabolic functionalities. The analysis of the metabolic pathways provides a mechanistic explanation of the remote mode of communication with systems, organs, and microflora of other body sites, including the ecosystem of the upper respiratory tract. This axis may have a role in the development of respiratory allergic disease. Notably, the microbiota is significant in the development and maintenance of barrier function; influences hematopoiesis and innate immunity; and shows its critical roles in Th1, Th2, and Treg production, which are necessary to maintain immunological balance and promote tolerance, taking part in every single step of the inflammatory cascade. These are microbial biotherapy foundations, starting from probiotics up to postbiotics and parabiotics, in a still-ongoing process. When considering the various determinants that can shape microbiota, there are several factors to consider: genetic factors, environment, mode of delivery, exposure to antibiotics, and other allergy-unrelated diseases. These factors hinder the engraftment of probiotic strains but may be upgradable with postbiotic and parabiotic administration directly on molecular targets. Supplementation with postbiotics and parabiotics could represent a very exciting perspective of treatment, bypassing probiotic limitations. At present, this avenue remains theoretical and to be explored, but it will certainly be a fascinating path to follow.

Background: Between June and July 2020, we evaluated children and adolescents concerning post-infection surveillance after a COVID-19 positivity during the lockdown. We aimed to assess whether the anamnestic presence of allergies could correlate with the presence of SARS-CoV-2 symptoms, and in particular with anosmia., Material and Methods: For each patient, we collected anamnestic data, the presence of allergies documented by performing skin prick tests, and COVID-19 symptoms. Then, if over six years of age, each patient underwent an active anterior rhinomanometry., Results: A total of 296 patients were enrolled, of whom 105 (35.4%) reported allergies. Considering COVID-19 symptoms, 74 subjects (25%) presented an asymptomatic form, 222 (75%) reported symptoms, and anosmia recurred in 60 subjects (27.03%). A statistically significant relationship was found between allergies and symptomatic COVID-19 ( p = 0.042), allergies, and anosmia ( p = 0.05), and allergies and anosmia in males ( p = 0.007). Moreover, anosmic patients presented a higher body mass index, older age, and a longer COVID-19 duration with statistical significance ( p = 0.001, 0.001, 0.006, respectively)., Conclusions: Allergic subjects seem to develop symptomatic COVID-19 more frequently and allergies appear to be a protective factor from anosmia's onset in males.

Aim: We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3-5 months after infection have psychological consequences that interfere with their adaptive functioning., Method: We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3-5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease., Results: At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3-5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5-5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6-18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID., Conclusions: These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents., Competing Interests: 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., (Copyright © 2022 Guido, Lucidi, Midulla, Zicari, Bove, Avenoso, Amedeo, Mancino, Nenna, De Castro, Capponi, Cinicola, Brindisi, Grisoni, Murciano, Spalice and the Long-Covid Group of Department of Maternal Sciences.)

Cow's milk allergy (CMA) is a common condition in the pediatric population. CMA can induce a diverse range of symptoms of variable intensity. It occurs mainly in the first year of life, and if the child is not breastfed, hypoallergenic formula is the dietary treatment. Extensively hydrolyzed cow's milk formulas (eHF) with documented hypo-allergenicity can be recommended as the first choice, while amino acid-based formulas (AAF) are recommended for patients with more severe symptoms. Hydrolyzed rice-based formulas (HRFs) are a suitable alternative for infants with CMA that cannot tolerate or do not like eHF and in infants with severe forms of CMA. In the present paper, we reviewed the nutritional composition of HRFs as well as studies regarding their efficacy and tolerance in children, and we provided an updated overview of the recent evidence on the use of HRFs in CMA. The available studies provide evidence that HRFs exhibit excellent efficacy and tolerance and seem to be adequate in providing normal growth in healthy children as well as in children with CMA., Competing Interests: The authors declare no conflict of interest.

Purpose: CD14 is involved in the modulation of immune reaction via toll-like receptors (TLR) and may influence the development of allergic diseases. The role of CD14 in vernal keratoconjunctivitis (VKC) has not yet been investigated. The aim of this study is to evaluate changes of tear soluble sCD14 and conjunctival CD14, TLR-4 and 9 expression in patients with VKC in the active and quiescent phases., Methods: Eighteen patients with VKC during active inflammation (group A, N  = 9), in the quiescent phase (group Q, N  = 5) and after recovery (group R, N  = 4) and 10 healthy subjects were included. Expression of sCD14 in tears and of CD14, TLR-4, and TLR-9 by conjunctival epithelium were evaluated by Western Blot in all groups., Results: Expression of tear sCD14 and of conjunctival CD14, TLR-4, and TLR-9 was significantly decreased in group A when compared with healthy subjects and with VKC group Q and R. Lower expression of sCD14, CD14, TLR-4, and TLR-9 were significantly correlated with the severity of papillary reaction, while the lower sCD14 was correlated with severity of conjunctival hyperemia., Conclusions: Tear sCD14, and conjunctival CD14, TLR4, and TLR-9 decreased during ocular surface inflammatory reaction in patients with VKC. CD14 and TLRs ocular surface evaluation may represent biomarkers of VKC activity and novel therapeutic target.

Vaccination against COVID-19 is the most effective tool to protect both the individual and the community from this potentially life-threatening infectious disease. Data from phase-3 trials showed that two doses of the BNT162b2 vaccine were safe, immunogenic, and effective against COVID-19 in children aged 5-11 years. However, no surveys in real-life settings have been carried out in this age range. Here, we conducted a cross-sectional study to evaluate the short-term adverse reactions (ARs) and the rate of protection against infection of the BNT162b2 vaccine in children aged 5-11 years by the compilation of two surveillance questionnaires conceived using Google Forms. Five-hundred and ninety one children were included in the analysis. ARs were reported by 68.9% of the children, being mainly local. The incidence of systemic ARs, especially fever, was higher after the second dose. The incidence of infection after completing the immunization accounted for 13.6% of the children. COVID-19 symptoms reported were mild, with the exception of one case of pneumonia. Only 40% of infected participants needed to take medication to relieve symptoms, mostly paracetamol and NSAIDs, and none reported persistent symptoms. The Pfizer-BioNTech vaccine in children aged 5-11 years is safe and well tolerated. The mild clinical course of COVID-19 in immunized children confirmed the favorable risk-benefit ratio, encouraging parents to immunize their children.

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although many reports have detailed a range of neurological symptoms in SARS-CoV-2-infected patients, studies of neuro-ophthalmological manifestations are still scarce., Case Presentation: We report a 9-year-old girl with abducens nerve palsy after COVID-19 with no evidence of other neurological disease on neuroimaging. At 2-month follow-up clinical conditions were improved., Conclusions: The palsy may have occurred due to a possible post-infectious immune-mediated mechanism underlying the neuropathy, as opposed to direct viral infiltration. Despite being rare, this complication must be taken into account., (© 2022. The Author(s).)

Background: COVID-19 lockdown caused sudden changes in people's lifestyle, as a consequence of the forced lockdown imposed by governments all over the world. We aimed to evaluate the impact of lockdown on body mass index (BMI) in a cohort of allergic children and adolescents., Methods: From the first of June until the end of October 2020, we submitted a written questionnaire to all the patients who, after lockdown, carried out a visit at the Pediatric Allergy Unit of the Department of Mother-Child, Urological Science, Sapienza University of Rome. The questionnaire was composed by 10 questions, referring to the changes in their daily activities. Data were extrapolated from the questionnaire and then analyzed considering six variables: BMI before and BMI after lockdown, sugar intake, sport, screens, sleep, and anxiety., Results: One hundred fifty-three patients agreed to answer our questionnaire. Results showed a statistically significant increase in the BMI after lockdown (20.97 kg/m2 ± 2.63) with respect to the BMI before lockdown (19.18 kg/m2 ± 2.70). A multivariate regression analysis showed that the two variables that mostly influenced the increase in BMI were sleep and anxiety., Conclusions: For the analyzed cohort of allergic children and adolescents we obtained significant gain in BMI as consequences of lockdown, which can be explained by many factors: high consumption of consolatory food, less sport activities, more time spent in front of screens, sleep alteration associated with increased anxiety. All these factors acted together, although sleep alteration and increased anxiety were the most influential factors that led to the worsening or the onset of weight gain, creating the basis for future health problems., (© 2022. The Author(s).)

Background: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown., Methods: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children's University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure., Results: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure., Conclusion: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions., (© 2022. The Author(s).)