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Children
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Childhood Innate Immunity and Infectious Diseases
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Childhood Innate Immunity and Infectious Diseases

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Infectious Diseases".

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 28215

Special Issue Editor

Dr. Danilo Buonsenso

E-Mail Website
Guest Editor
1. Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
2. Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
3. Global Health Research Institute, Istituto di Igiene, Università Cattolica del Sacro Cuore, Rome, Italy
Interests: pediatric infectious diseases; global health; point of care ultrasound applied to infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite countless discoveries in medical sciences during the last few decades, several questions still remain unanswered. Unfortunately, the ongoing SARS-CoV-2 pandemic has opened the pandora’s box and reminded us of how much we still have to learn in several fields, from public health policies to basic science. Among the latter, the immune system is definitely among the protagonists. SARS-CoV-2, initially thought to cause a severe pneumonia (1), is now linked to a more complex systemic disorder where inflammation plays a primary role, causing a cytokine storm (2), endothelial inflammation predisposing to microclots (3), and countless more clinical effects. Not by chance, the majority of treatments studied have specific immune targets, and the most effective treatments so far, according to the higher standard of research, are once again steroids (4).

However, something is complicating the picture even more. Why are children, so far, less affected by the SARS-CoV-2 pandemic and frequently develop asymptomatic or paucisymptomatic infections? (5) Why is this happening, when millions of children die every year from other infectious diseases, including viruses? Why do some of them develop, weeks after the initial infection, a multisystem inflammatory syndrome? (6)

The immune system definitely hides the answers to these (7).

This pandemic is posing countless challenges for all of us, but it is also giving us the opportunity to learn more and, hopefully, prepare a better future to next generations. As members of the scientific community, we aim to take the chance to learn more, train new generations of healthcare workers, and inspire. This is why we are calling you to contribute to a Special Issue on “Childhood Innate Immunity and Infectious Diseases”, aiming to provide both high-quality reviews and original studies that both educate and inspire the scientific community and the younger generation of healthcare workers and researchers.

We are particularly interested in the following topics:

  • Innate immunity from the newborns to adolescents (reviews and new findings);
  • Innate immunity, BCG, and tuberculosis;
  • Innate immunity and immunizations;
  • Innate immunity and bacterial infections of major pediatric interest;
  • Innate immunity and viral infections of major pediatric interest, including SARS-CoV-2;
  • Childhood microbiota and innate immunity.

Dr. Danilo Buonsenso
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Immune system
  • Microbiota
  • Innate immunity
  • Viral infections
  • Bacterial infections
  • Immunizations

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (9 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 201 KiB  
Editorial
Childhood Immunity and Infections: Time to Consider Endothelial Cells and Platelets
by Danilo Buonsenso
Children 2022, 9(6), 841; https://doi.org/10.3390/children9060841 - 6 Jun 2022
Viewed by 1776
Abstract
The immune system was, and still is, the protagonist of this pandemic [...] Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)

Research

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7 pages, 467 KiB  
Article
Tuberculosis in Adolescents in Bulgaria for a Three-Year Period: 2018–2020
by Natalia Gabrovska, Albena Spasova, Anabela Galacheva, Dimitar Kostadinov, Nikolay Yanev, Vladimir Milanov, Kaloyan Gabrovski and Svetlana Velizarova
Children 2022, 9(6), 785; https://doi.org/10.3390/children9060785 - 26 May 2022
Cited by 1 | Viewed by 1922
Abstract
Background: Each year, approximately two million adolescents and young adults in the world become infected with tuberculosis (TB). The problem is that the classification of the disease includes children in the age group 0–14 years and young adults aged 15 and over. The [...] Read more.
Background: Each year, approximately two million adolescents and young adults in the world become infected with tuberculosis (TB). The problem is that the classification of the disease includes children in the age group 0–14 years and young adults aged 15 and over. The present study aims to analyze and compare the epidemiology and clinical presentation of TB in Bulgaria in the different age subgroups of childhood. Methods: A retrospective study was undertaken of the newly diagnosed children (n = 80) with TB treated onsite from January 2018 to December 2020 at the Multiprofile Hospital for Active Treatment of Pulmonary Diseases (“St. Sofia”). They were distributed into three age groups: aged 8–11 (prepuberty), aged 12–14 (younger adolescents), and aged above 15 (older adolescents). Results: A clear finding of the research indicated that adolescent children develop TB both as primary and secondary infections. In a large number of cases with the children under our care, we found enlarged intrathoracic lymph nodes as well as infiltrative changes in the lungs, i.e., we observed transitional forms. There were statistically significant differences between the age group >15 years old and each of the other two younger groups for diagnosis, the severity of intoxication, and BK spreading status. Conclusion: The course of tuberculosis in adolescence has its own specifics and differences between the three age groups in the current study. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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11 pages, 1806 KiB  
Article
Is Early Surgical Intervention Necessary for Acute Neonatal Humeral Epiphyseal Osteomyelitis: A Retrospective Study of 31 Patients
by Yun Gao, Ruikang Liu, Saroj Rai, Qingtuan Liang, Yuan Liu, Xiaoliang Xiao and Pan Hong
Children 2022, 9(4), 527; https://doi.org/10.3390/children9040527 - 7 Apr 2022
Cited by 4 | Viewed by 2466
Abstract
Objective: To review the treatment experience of neonatal humeral epiphyseal osteomyelitis retrospectively. Study design: Retrospective cohort study of infants with neonatal humeral epiphyseal osteomyelitis. Patients were divided into conservative group and surgical group, and the surgical group was subdivided into early and delayed [...] Read more.
Objective: To review the treatment experience of neonatal humeral epiphyseal osteomyelitis retrospectively. Study design: Retrospective cohort study of infants with neonatal humeral epiphyseal osteomyelitis. Patients were divided into conservative group and surgical group, and the surgical group was subdivided into early and delayed surgical group. Results: In total, there were 7 patients in the conservative group and 24 in the surgical group. The length of hospital stay and intravenous course of antibiotic therapy were both significantly shorter in the surgical group (p < 0.001). The full recovery rate was also higher in the surgical group (83.3%) than the conservative group (14.3%) (p < 0.001). Early surgery group (n = 14) had an insignificantly higher positive rate of pus/aspirate culture and full recovery rate than delayed surgery group (n = 10). Conclusion: Surgical treatment for neonatal humeral epiphyseal osteomyelitis demonstrated significantly higher rates of positive culture for the pathogen, a shorter course of intravenous oral antibiotics, and lower incidence of growth abnormality than conservative treatment. In our institution, most of culture outcome Gram-positive bacteria, and early surgical treatment was recommended with better outcome than delayed surgical group. Empirical antibiotics should be tailored to the epidemiological characteristics of local virulent bacteria. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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6 pages, 228 KiB  
Communication
Safety of Monoclonal Antibodies in Children Affected by SARS-CoV-2 Infection
by Lorenza Romani, Francesca Ippolita Calò Carducci, Sara Chiurchiù, Laura Cursi, Maia De Luca, Martina Di Giuseppe, Andrzej Krzysztofiak, Laura Lancella, Paolo Palma, Leonardo Vallesi, Tiziana Corsetti, Andrea Campana, Emanuele Nicastri, Paolo Rossi and Stefania Bernardi
Children 2022, 9(3), 369; https://doi.org/10.3390/children9030369 - 7 Mar 2022
Cited by 15 | Viewed by 2985
Abstract
Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment [...] Read more.
Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment for SARS-CoV-2 infection in children aged from 24 days to 18 years old. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
13 pages, 1726 KiB  
Article
Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study
by Danilo Buonsenso, Francesco Mariani, Luca Pierri, Rosa Morello, Adriana Yock-Corrales, Olguita Del Aguila, Ilaria Lazzareschi, Giuseppe Zampino, Francesco Nunziata, Piero Valentini and Andrea Lo Vecchio
Children 2022, 9(2), 279; https://doi.org/10.3390/children9020279 - 17 Feb 2022
Cited by 16 | Viewed by 4026
Abstract
Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We [...] Read more.
Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62–10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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9 pages, 1110 KiB  
Article
Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area
by Luca Pierantoni, Laura Andreozzi, Simone Ambretti, Arianna Dondi, Carlotta Biagi, Francesco Baccelli and Marcello Lanari
Children 2021, 8(7), 597; https://doi.org/10.3390/children8070597 - 14 Jul 2021
Cited by 8 | Viewed by 2854
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. [...] Read more.
Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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Review

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10 pages, 268 KiB  
Review
The Relationship between COVID-19 and Innate Immunity in Children: A Review
by Piero Valentini, Giorgio Sodero and Danilo Buonsenso
Children 2021, 8(4), 266; https://doi.org/10.3390/children8040266 - 30 Mar 2021
Cited by 20 | Viewed by 5835
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the pandemic viral pneumonia that was first identified in Wuhan, China, in December 2019, and has since rapidly spread around the world. The number of COVID-19 cases recorded in pediatric age [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the pandemic viral pneumonia that was first identified in Wuhan, China, in December 2019, and has since rapidly spread around the world. The number of COVID-19 cases recorded in pediatric age is around 1% of the total. The immunological mechanisms that lead to a lower susceptibility or severity of pediatric patients are not entirely clear. At the same time, the immune dysregulation found in those children who developed the multisystem inflammatory syndrome (MIC-S) is not yet fully understood. The aim of this review is to analyze the possible influence of children’s innate immune systems, considering the risk of contracting the virus, spreading it, and developing symptomatic disease or complications related to infection. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)

Other

8 pages, 744 KiB  
Brief Report
Defective Leukocyte β2 Integrin Expression and Reactive Oxygen Species Production in Neonates
by Irma Capolupo, Domenico Umberto De Rose, Roberto Pascone, Olivier Danhaive and Marcello Orzalesi
Children 2022, 9(4), 494; https://doi.org/10.3390/children9040494 - 1 Apr 2022
Cited by 1 | Viewed by 1890
Abstract
Neonates are highly susceptible to bacterial infections, which represent a major source of mortality and morbidity in this age category. It is recognized that β2 integrins play a critical role in innate immunity by mediating leukocyte vascular adhesion, transmigration and bacterial phagocytosis. Therefore, [...] Read more.
Neonates are highly susceptible to bacterial infections, which represent a major source of mortality and morbidity in this age category. It is recognized that β2 integrins play a critical role in innate immunity by mediating leukocyte vascular adhesion, transmigration and bacterial phagocytosis. Therefore, we aimed to assess if the impaired immune functions seen in newborns may derive, in part, from a transient insufficient β2 integrin expression. In the present study we measured baseline lymphocyte function-associated antigen-1 (LFA-1 or CD11a/CD18), macrophage-1 antigen (MAC-1 or CD11b/CD18) and leukocyte integrin p150-95 (CD11c/CD18) expression on cord blood, and on the third day of life in a cohort of 35 healthy neonates, compared with a control group of 12 healthy adults. For any of the three β2 integrins, the expression on polymorphonuclear cells was significantly lower on cord blood than in adults and increased from birth to day 3. We also compared superoxide radical (SR) production in these neonates with 28 non-smoking adults. SR production in response to integrin stimulation by Zymosan was significantly lower at birth than in adults, and it decreased further in the third day of life. These findings suggest that innate immune impairment in newborns may be, in part, accounted for by a lower β2 integrin expression on phagocytes in the neonatal period, but also by a functional impairment of free radical production. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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5 pages, 1082 KiB  
Case Report
A Case of Tracheal Stenosis as an Isolated Form of Immunoproliferative Hyper-IgG4 Disease in a 17-Year-Old Girl
by Natalia Gabrovska, Svetlana Velizarova, Albena Spasova, Dimitar Kostadinov, Nikolay Yanev, Hristo Shivachev, Edmond Rangelov, Yanko Pahnev, Zdravka Antonova, Nikola Kartulev, Ivan Terziev and Kaloyan Gabrovski
Children 2021, 8(7), 589; https://doi.org/10.3390/children8070589 - 12 Jul 2021
Cited by 3 | Viewed by 2799
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a lymphoproliferative disease which is described almost exclusively in adults. There are only a few pediatric patients who have been observed with this disorder. Here, we describe a rare case of IgG4-RD in a 17-year-old girl with a [...] Read more.
Immunoglobulin G4-related disease (IgG4-RD) is a lymphoproliferative disease which is described almost exclusively in adults. There are only a few pediatric patients who have been observed with this disorder. Here, we describe a rare case of IgG4-RD in a 17-year-old girl with a single manifestation—tracheal stenosis without previous intubation or other inciting event. She had mixed dyspnea and noisy and weakened breathing. Immunoproliferative hyper-IgG4 disease was diagnosed, based on elevated serum IgG4 and histological findings. Until now we have chosen to treat the girl only with corticosteroids with a good response so far. The general condition as well as the respiratory function are regularly monitored. The tracheal involvement of IgG4-RD is uncommon. Nonetheless, it is a manifestation that should be included in the differential diagnosis of tracheal stenosis. Full article
(This article belongs to the Special Issue Childhood Innate Immunity and Infectious Diseases)
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