Gastroenteritis Is Less Severe But Is More Often Associated With Systemic Inflammation in SARS-CoV-2-positive Than in SARS-CoV-2-negative Children.

This study aims to characterize the clinical and metabolic features of acute gastroenteritis in children with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A multicenter case-control study was conducted in 2022 including 200 children. Clinical data and laboratory tests were analyzed. Children with SARS-CoV-2 presented less frequently hyponatremia and metabolic acidosis, but more often systemic inflammation as compared with children without SARS-CoV-2.

Information and Training on the Use of Telemedicine in Pediatric Population: Consensus Document of the Italian Society of Telemedicine (SIT), of the Italian Society of Preventive and Social Pediatrics (SIPPS), of the Italian Society of Pediatric Primary Care (SICuPP), of the Italian Federation of Pediatric Doctors (FIMP), and of the Syndicate of Family Pediatrician Doctors (SIMPeF).

Telemedicine has entered the daily lives of doctors, although the digital skills of healthcare professionals still remain a goal to be achieved. For the purpose of a large-scale development of telemedicine, it is necessary to create trust in the services it can offer and to favor their acceptance by healthcare professionals and patients. In this context, information for the patient regarding the use of telemedicine, the benefits that can be derived from it, and the training of healthcare professionals and patients for the use of new technologies are fundamental aspects. This consensus document is a commentary that has the aim of defining the information on and training aspects of telemedicine for pediatric patients and their caregivers, as well as pediatricians and other health professionals who deal with minors. For the present and the future of digital healthcare, there is a need for a growth in the skills of professionals and a lifelong learning approach throughout the professional life. Therefore, information and training actions are important to guarantee the necessary professionalism and knowledge of the tools, as well as a good understanding of the interactive context in which they are used. Furthermore, medical skills can also be integrated with the skills of various professionals (engineers, physicists, statisticians, and mathematicians) to birth a new category of health professionals responsible for building new semiotics, identifying criteria for predictive models to be integrated into clinical practice, standardizing clinical and research databases, and defining the boundaries of social networks and new communication technologies within health services.

Clinical Presentation and Severity of SARS-CoV-2 Infection Compared to Respiratory Syncytial Virus and Other Viral Respiratory Infections in Children Less than Two Years of Age.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the implementation of restrictive measures led to a dramatic reduction in respiratory syncytial virus (RSV) occurrence together with rare and mild bronchiolitis induced by SARS-CoV-2. We described the respiratory picture of SARS-CoV-2 infection and evaluated the frequency and the severity of SARS-CoV-2 bronchiolitis comparing it with other respiratory viral infections in children less than two years of age. The severity of respiratory involvement was evaluated based on the need for oxygen therapy, intravenous hydration, and the length of hospital stay. A total of 138 children hospitalized for respiratory symptoms were enrolled: 60 with SARS-CoV-2 and 78 with RSV. In the group of SARS-CoV-2-infected children, 13/60 (21%) received a diagnosis of co-infection. Among the enrolled children, 87/138 (63%) received a diagnosis of bronchiolitis. The comparative evaluation showed a higher risk of the need for oxygen therapy and intravenous hydration in children with RSV infection and co-infection compared to children with SARS-CoV-2 infection. In the children with a diagnosis of bronchiolitis, no differences in the main outcomes among the groups were observed. Although children with SARS-CoV-2 infection have less severe respiratory effects than adults, the pediatrician should pay attention to bronchiolitis due to SARS-CoV-2, which could have a severe clinical course in younger children.

Diarrhea Is a Hallmark of Inflammation in Pediatric COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogen with enteric tropism. We compared the clinical, biochemical and radiological features of children hospitalized for acute SARS-CoV-2 infection, classified in two groups based on the presence of diarrhea. Logistic regression analyses were used to investigate the variables associated with diarrhea. Overall, 407 children were included in the study (226 males, 55.5%, mean age 3.9 ± 5.0 years), of whom 77 (18.9%) presented with diarrhea, which was mild in most cases. Diarrhea prevalence was higher during the Alpha (23.6%) and Delta waves (21.9%), and in children aged 5-11 y (23.8%). Other gastrointestinal symptoms were most commonly reported in children with diarrhea (p < 0.05). Children with diarrhea showed an increased systemic inflammatory state (higher C-reactive protein, procalcitonin and ferritin levels, p < 0.005), higher local inflammation as judged by mesenteric fat hyperechogenicity (adjusted Odds Ratio 3.31, 95%CI 1.13-9.70) and a lower chance of previous immunosuppressive state (adjusted Odds Ratio 0.19, 95%CI 0.05-0.70). Diarrhea is a frequent feature of pediatric COVID-19 and is associated with increased systemic inflammation, which is related to the local mesenteric fat inflammatory response, confirming the implication of the gut not only in multisystem inflammatory syndrome but also in the acute phase of the infection.

SARS-CoV-2 causes secretory diarrhea with an enterotoxin-like mechanism, which is reduced by diosmectite.

Background and aims: The pathophysiology of SARS-CoV-2-associated diarrhea is unknown. Using an experimental model validated for rotavirus-induced diarrhea, we investigated the effects of SARS-CoV-2 on transepithelial ion fluxes and epithelial integrity of human intestinal cells. The effect of the antidiarrheal agent diosmectite on secretion was also evaluated following its inclusion in COVID-19 management protocols. Methods: We evaluated electrical parameters (intensity of short-circuit current [Isc] and transepithelial electrical resistance [TEER]) in polarized Caco-2 cells and in colonic specimens mounted in Ussing chambers after exposure to heat-inactivated (hi) SARS-CoV-2 and spike protein. Spectrofluorometry was used to measure reactive oxygen species (ROS), a marker of oxidative stress. Experiments were repeated after pretreatment with diosmectite, an antidiarrheal drug used in COVID-19 patients. Results: hiSARS-CoV-2 induced an increase in Isc when added to the mucosal (but not serosal) side of Caco-2 cells. The effect was inhibited in the absence of chloride and calcium and by the mucosal addition of the Ca2+-activated Cl- channel inhibitor A01, suggesting calcium-dependent chloride secretion. Spike protein had a lower, but similar, effect on Isc. The findings were consistent when repeated in human colonic mucosa specimens. Neither hiSARS-CoV-2 nor spike protein affected TEER, indicating epithelial integrity; both increased ROS production. Pretreatment with diosmectite inhibited the secretory effect and significantly reduced ROS of both hiSARS-CoV-2 and spike protein. Conclusions: SARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.

Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome.

Importance: Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective: To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants: A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase-polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures: The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results: Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98-7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child's age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance: In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications.

Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion.

SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.

No Spread of SARS-CoV-2 From Infected Symptomatic Children to Parents: A Prospective Cohort Study in a Controlled Hospital Setting.

Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions. Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period. Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0-6.2, range 0.1-17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days. Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.

Risk of SARS-CoV-2 Transmission in Health Care Personnel Working in a Pediatric COVID-19 Unit.

OBJECTIVES: The paucity of symptoms and the difficulties in wearing personal protective equipment make children a potential source of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for health care workers (HCWs). Previous experience in pediatric settings reported high rate of intrahospital SARS-CoV-2 transmission in HCWs caring for children. We aimed at investigating the rate and determinants of SARS-CoV-2 infection among HCWs working in a regional reference center in the Southern Italy. METHODS: A prospective observational study was conducted to monitor the occurrence of SARS-CoV-2 infections among HCWs and investigate the relation between the infection rate and hours of exposure or number and characteristics of procedures, including nasopharyngeal swab, high-flow oxygen delivery, suctioning of airway secretions, sputum induction, and nebulizer administration. RESULTS: After 5 months of monitoring, 425.6 hours of SARS-CoV-2 exposure (18.5 hours per person), and 920 hospital procedures, no case of nosocomial transmission was reported among the 23 HCWs enrolled in the study. CONCLUSIONS: The application of stringent preventive measures, also outside the area dedicated to patients' care, can effectively control infection spreading also in pediatric settings.

Health-care organization for the management and surveillance of SARS-CoV-2 infection in children during pandemic in Campania region, Italy.

BACKGROUND: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. METHODS: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. RESULT: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2-9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5-19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. CONCLUSION: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.

Is Quarantine for COVID-19 Pandemic Associated with Psychological Burden in Primary Ciliary Dyskinesia?

BACKGROUND: Information on psychological impact of COVID-19 quarantine in primary ciliary dyskinesia (PCD), a chronic disorder with recurrent pulmonary exacerbations, is lacking. Psychological well-being was prospectively assessed during COVID-19 lockdown in Italy in a PCD population. METHODS: we recruited 27 PCD patients and 27 healthy controls. To assess psychological well-being, psychological general well-being index and parenting stress index-short questionnaires were administered to participants ≥15 years-old and to mothers of participants <15 years-old, respectively. The PCD exacerbations since outbreak onset and frequency of quarantine weekly chest physiotherapy were compared to the same period of 2019. OUTCOMES: 70% of PCD mothers and 90% of PCD patients did not show parental stress levels or distress levels, respectively, and these groups showed no significant difference in stress compared to controls. The PCD pulmonary exacerbations occurred less frequently and weekly chest physiotherapy sessions significantly increased compared to the same period during 2019 (p < 0.05). INTERPRETATION: During COVID-19 quarantine, a PCD population showed psychological well-being. Low exacerbation rate, explained by lower infectious exposure or improved compliance to chest physiotherapy, likely contributed to psychological well-being. Evaluating psychological burden and parental stress is a valuable tool for measuring the emotional impact of PCD and improving PCD medical care.

Is Quarantine for COVID-19 Pandemic Associated with Psychological Burden in Primary Ciliary Dyskinesia?

Background: Information on psychological impact of COVID-19 quarantine in primary ciliary dyskinesia (PCD), a chronic disorder with recurrent pulmonary exacerbations, is lacking. Psychological well-being was prospectively assessed during COVID-19 lockdown in Italy in a PCD population. Methods: we recruited 27 PCD patients and 27 healthy controls. To assess psychological well-being, psychological general well-being index and parenting stress index-short questionnaires were administered to participants ≥15 years-old and to mothers of participants <15 years-old, respectively. The PCD exacerbations since outbreak onset and frequency of quarantine weekly chest physiotherapy were compared to the same period of 2019. Outcomes: 70% of PCD mothers and 90% of PCD patients did not show parental stress levels or distress levels, respectively, and these groups showed no significant difference in stress compared to controls. The PCD pulmonary exacerbations occurred less frequently and weekly chest physiotherapy sessions significantly increased compared to the same period during 2019 (p <0.05). Interpretation: During COVID-19 quarantine, a PCD population showed psychological well-being. Low exacerbation rate, explained by lower infectious exposure or improved compliance to chest physiotherapy, likely contributed to psychological well-being. Evaluating psychological burden and parental stress is a valuable tool for measuring the emotional impact of PCD and improving PCD medical care.