Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Epidemiology of Respiratory Infections during the COVID-19 Pandemic.

To face the COVID-19 outbreak, a wide range of non-pharmaceutical interventions (NPIs) aimed at limiting the spread of the virus in communities, such as mask-wearing, hand hygiene, social distancing, travel restrictions, and school closures, were introduced in most countries. Thereafter, a significant reduction of new asymptomatic and symptomatic COVID-19 cases occurred, although there were differences between countries according to the type and duration of the NPIs. In addition, the COVID-19 pandemic has been accompanied by significant variations in the global incidence of diseases due to the most common non-SARS-CoV-2 respiratory viruses and some bacteria. In this narrative review, the epidemiology of the most common non-SARS-CoV-2 respiratory infections during the COVID-19 pandemic is detailed. Moreover, factors that could have had a role in modifying the traditional circulation of respiratory pathogens are discussed. A literature analysis shows that NPIs were the most important cause of the general reduction in the incidence of influenza and respiratory syncytial virus infection in the first year of the pandemic, although the different sensitivity of each virus to NPIs, the type and duration of measures used, as well as the interference among viruses may have played a role in modulating viral circulation. Reasons for the increase in the incidences of Streptococcus pneumoniae and group A Streptococcus infections seem strictly linked to immunity debt and the role played by NPIs in reducing viral infections and limiting bacterial superimposed infections. These results highlight the importance of NPIs during pandemics, the need to monitor the circulation of infectious agents that cause diseases similar to those caused by pandemic agents, and the need to make efforts to improve coverage with available vaccines.

Update on COVID-19 Therapy in Pediatric Age.

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.

Knowledge on Parental Hesitancy toward COVID-19 Vaccination of Children 5-11 Years Old.

Although vaccines are the safest and the most effective measure to prevent disease, disability, and death from various pediatric infectious diseases, parental vaccine hesitancy is a common and increasing phenomenon worldwide. To contribute to improving our knowledge on parental willingness and hesitancy toward COVID-19 vaccine administration in children aged 5-11 years, an anonymous online questionnaire was disseminated in Italy after the COVID-19 vaccine's authorization for this age group. An online survey was conducted using the Crowd Signal platform from 15 December 2021 to 15 January 2022 in Italy among parents of children 5-11 years old. A total of 3433 questionnaires were analyzed. Overall, a "Favorable" position was observed in 1459 (42.5%) parents, a "Doubtful" one in 1223 (35.6%) and a "Hesitant/Reluctant" one in 751 (21.9%). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, mostly female, with a secondary or middle school degree, an annual income below EUR 28,000, more than one child in the age range from 5 to 11 years, an underestimated consideration of the severity of COVID-19's effects, and concern regarding the COVID-19 vaccines in general. These results show that in Italy, most parents of children aged 5 to 11 were doubtful or hesitant/reluctant to vaccinate their children against the COVID-19 virus. Poor trust in health institutions as well as poor consideration of the epidemiological and clinical relevance of COVID-19 in children seem to have played the biggest roles in forming these attitudes. Moreover, the negative attitude of several parents who previously agreed to immunize their children against other childhood illnesses according to the official national pediatric immunization schedule clearly indicates that only the COVID-19 vaccine was put in doubt or rejected. All these findings lead us to conclude that to improve COVID-19 vaccination coverage in children aged 5 to 11, health authorities should increase parental education on the true clinical relevance of COVID-19 and on the importance of its prevention to hinder the evolution of the pandemic in pediatric subjects and the emergence of new variants, and its relative weight in influencing the efficacy of vaccines.

Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?

BACKGROUND: Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development. MAIN FINDINGS: Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates. CONCLUSIONS: Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.

Can we get out of the COVID pandemic without adequate vaccination coverage in the pediatric population?

BACKGROUND: During the first and second COVID-19 pandemic waves, children, despite susceptible to SARS-CoV-2 infection, appeared at lower risk of severe disease, hospitalization, and death than adults and the elderly. Moreover, they seemed to play a minor role in the diffusion of the virus. The aim of this manuscript is to show epidemiological surveillance on COVID-19 incidence and hospitalization in the pediatric cohort in order to explain the importance of an adequate COVID-19 vaccination coverage in the pediatric population. METHODS: All subjects with documented SARS-CoV-2 infection diagnosed in Parma, Italy, between February 21st, 2020, and January, 31st, 2022, were recruited in this epidemiological surveillance. Diagnosis of infection was established in presence of at least one respiratory specimen positive for SARS-CoV-2 nucleic acid using a validated real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay. RESULTS: The number of COVID-19 pediatric cases remained very low and lower than that recorded in the general population between early February 2020 and the end of October 2021, despite in the last part of this period the Delta variant emerged. On the contrary, starting from November 2021, a sharp and significant increase in COVID-19 incidence in the pediatric population was evidenced. This was detected in all the age groups, although greater in the populations aged 5-11 and 12-17 years old. Interestingly, the peak in hospitalization rate was observed in children < 5 years old, for whom COVID-19 vaccination is not approved yet. At the beginning of November 2021 among people older than 18 years of age 85.7% had completed the primary series of COVID-19 vaccine. Almost all the infants and pre-school children were susceptible. Until January 31st, 2022, 80.4% of adolescents aged 11-17 years had received at least two doses of COVID-19 vaccine and only 52.4% received the booster. Among children 5-11 years old, on January 31st, 2022, only 28.5% had received at least one vaccine dose. CONCLUSIONS: Compared with adults and the elderly, presently a greater proportion of children and adolescents is susceptible to SARS-CoV-2 and could play a relevant role for the prolongation of the COVID-19 pandemic. Only a rapid increase in vaccination coverage of the pediatric populations can effectively counter this problem.

Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence.

Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.

Myocarditis Following COVID-19 Vaccine Use: Can It Play a Role for Conditioning Immunization Schedules?

Myocarditis (MYO) is a relatively uncommon inflammatory disease that involves the heart muscle. It can be a very severe disease as it can lead to the development of acute or chronic heart failure and, in a not marginal number of cases, to death. Most of the cases are diagnosed in healthy people younger than 30 years of age. Moreover, males are affected about twice as much as females. Viruses are among the most common causes of MYO, but how viral infection can lead to MYO development is not precisely defined. After COVID-19 pandemic declaration, incidence rate of MYO has significantly increased worldwide because of the SARS-CoV-2 infection. After the introduction of anti-COVID-19 vaccines, reports of post-immunization MYO have emerged, suggesting that a further cause of MYO together with the SARS-CoV-2 infection could increase the risk of heart damage during pandemic. Main aim of this study is to discuss present knowledge regarding etiopathogenesis and clinical findings of MYO associated with COVID-19 vaccine administration and whether the risk of this adverse events can modify the initially suggested recommendation for the use of COVID-19 vaccines in pediatric age. Literature analysis showed that MYO is an adverse event that can follow the COVID-19 immunization with mRNA vaccines in few persons, particularly young adults, adolescents, and older children. It is generally a mild disease that should not modify the present recommendations for immunization with the authorized COVID-19 mRNA vaccines. Despite this, further studies are needed to evaluate presently undefined aspects of MYO development after COVID-19 vaccine administration and reduce the risk of development of this kind of vaccine complication. Together with a better definition of the true incidence of MYO and the exact role of the various factors in conditioning incidence variations, it is essential to establish long-term evolution of acute COVID-19 related MYO.

COVID-19 in Children: Update on Diagnosis and Management.

In December 2019, a new infectious disease called coronavirus disease 2019 (COVID-19) attributed to the new virus named severe scute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected. The gold standard for the diagnosis of SARS-CoV-2 infection is the viral identification in nasopharyngeal swab by real-time polymerase chain reaction. Few data on the role of imaging are available in the pediatric population. Similarly, considering that symptomatic therapy is adequate in most of the pediatric patients with COVID-19, few pediatric pharmacological studies are available. The main aim of this review is to describe and discuss the scientific literature on various imaging approaches and therapeutic management in children and adolescents affected by COVID-19. Clinical manifestations of COVID-19 are less severe in children than in adults and as a consequence the radiologic findings are less marked. If imaging is needed, chest radiography is the first imaging modality of choice in the presence of moderate-to-severe symptoms. Regarding therapy, acetaminophen or ibuprofen are appropriate for the vast majority of pediatric patients. Other drugs should be prescribed following an appropriate individualized approach. Due to the characteristics of COVID-19 in pediatric age, the importance of strengthening the network between hospital and territorial pediatrics for an appropriate diagnosis and therapeutic management represents a priority.

Italian intersociety consensus on management of long covid in children.

BACKGROUND: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. MAIN FINDINGS: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. CONCLUSIONS: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.

New Approaches and Technologies to Improve Accuracy of Acute Otitis Media Diagnosis.

Several studies have shown that in recent years incidence of acute otitis media (AOM) has declined worldwide. However, related medical, social, and economic problems for patients, their families, and society remain very high. Better knowledge of potential risk factors for AOM development and more effective preventive interventions, particularly in AOM-prone children, can further reduce disease incidence. However, a more accurate AOM diagnosis seems essential to achieve this goal. Diagnostic uncertainty is common, and to avoid risks related to a disease caused mainly by bacteria, several children without AOM are treated with antibiotics and followed as true AOM cases. The main objective of this manuscript is to discuss the most common difficulties that presently limit accurate AOM diagnosis and the new approaches and technologies that have been proposed to improve disease detection. We showed that misdiagnosis can be dangerous or lead to relevant therapeutic mistakes. The need to improve AOM diagnosis has allowed the identification of a long list of technologies to visualize and evaluate the tympanic membrane and to assess middle-ear effusion. Most of the new instruments, including light field otoscopy, optical coherence tomography, low-coherence interferometry, and Raman spectroscopy, are far from being introduced in clinical practice. Video-otoscopy can be effective, especially when it is used in association with telemedicine, parents' cooperation, and artificial intelligence. Introduction of otologic telemedicine and use of artificial intelligence among pediatricians and ENT specialists must be strongly promoted in order to reduce mistakes in AOM diagnosis.

Is the Immunization of Pregnant Women against COVID-19 Justified?

Maternal immunization against some infectious diseases can offer significant advantages for women, preventing maternal morbidity and mortality, or for offspring, preventing fetal disease and conferring passive immunity to neonates. Recently, clinical trials specifically to evaluate the immunogenicity, safety, and tolerability of some of the available coronavirus disease 2019 (COVID-19) vaccines in pregnant and lactating women have been planned, initiated and, in some cases, completed. This paper discusses whether the immunization of pregnant women against COVID-19 is justified and presents knowledge about the immunogenicity and safety of mRNA COVID-19 vaccines for these subjects. The results of recent studies indicate that pregnant women are at increased risk of developing severe disease compared with nonpregnant women of the same age. Studies carried out with mRNA vaccines indicate that the immunogenicity, safety and tolerability of these preventive measures in pregnant women are not different from those in nonpregnant women of the same age. Moreover, antibodies are efficiently transferred through the placenta and can be detected in breastmilk, suggesting a potential prevention of infection in the child. All these findings authorize the use of mRNA vaccines in pregnant women to protect both the mother and the child. However, further studies with larger sample size and with follow-up of the pregnant women vaccinated during different periods of pregnancy and their children are needed to better characterize the immune response of pregnant women, to define when these vaccines should be administered to obtain the best protection, and to measure vaccine efficacy against virus variants in both mothers and infants. COVID-19 vaccines based on different technological platforms cannot presently be used, and their role in pregnant women should be clarified.

Vaccines in Children with Inflammatory Bowel Disease: Brief Review.

Incidence of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Children with IBDs have a dysfunctional immune system and they are frequently treated with immunomodulating drugs and biological therapy, which significantly impair immune system functions and lead to an increased risk of infections. Vaccines are essential to prevent at least part of these infections and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended. However, several factors might lead to insufficient immunization. In this paper, present knowledge on the use of vaccines in children with IBDs is discussed. Literature review showed that despite a lack of detailed quantification of the risk of infections in children with IBDs, these children might have infections more frequently than age-matched healthy subjects, and at least in some cases, these infections might be even more severe. Fortunately, most of these infections could be prevented when recommended schedules of immunization are carefully followed. Vaccines given to children with IBDs generally have adequate immunogenicity and safety. Attention must be paid to live attenuated vaccines that can be administered only to children without or with mild immune system function impairment. Vaccination of their caregivers is also recommended. Unfortunately, compliance to these recommendations is generally low and multidisciplinary educational programs to improve vaccination coverage must be planned, in order to protect children with IBD from vaccine-preventable diseases.

Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities.

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.

Epidemiology of SARS-CoV-2 Infection Evaluated by Immunochromatographic Rapid Testing for the Determination of IgM and IgG Against SARS-CoV-2 in a Cohort of Mask Wearing Workers in the Metal-Mechanical Sector in an Area With a High Incidence of COVID-19.

Background: Although the diagnosis of new coronavirus 2019 (COVID-19) is made through the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory secretions by means of molecular methods, a more accurate estimation of SARS-CoV-2 circulation can be obtained by seroprevalence studies. The main aim of this study was to evaluate the true epidemiology of SARS-CoV-2 infection among workers in the metal-mechanical sector who never stopped working during the pandemic period in an area with a high incidence of COVID-19 and to define whether and how they could continue the work without appreciable risks during a second wave. Methods: A total of 815 metal-mechanical workers who had never stopped working even during the pandemic period in three different factories in the Emilia-Romagna Region, Italy, and who had always used face masks during working hours, underwent a capillary blood rapid test for the determination of IgM and IgG against SARS-CoV-2 (COVID-19 IgG/IgM Rapid test, PrimaLab, Modena, Italy). In the event of a positive test, a nasopharyngeal was performed and tested for the presence of SARS-CoV-2. Results: The detection of serum IgG/IgM against SARS-CoV-2 was significantly more common among workers employed in Parma (21/345, 6.1%) than among those employed in Calerno (7/242, 2.9%) or in Spilamberto (3/228, 1.3%) (p <0.001). The analysis of the role of the different variables as predictors of seropositivity for IgG/IgM against SARS-CoV-2 revealed that the presence of specific antibodies was strictly associated with a previous history of COVID-19-like symptoms (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.9-8.2) and household members with COVID-19-like symptoms (OR 2.20, 95% CI 1.04-4.82). Conclusion: This study shows that seropositivity to SARS-CoV-2 is low even among employees who did not interrupt their work during the lockdown phase in a region with a high incidence of COVID-19. The use of face masks appears effective in the avoidance of the transmission of SARS-CoV-2 in factories even in the presence of asymptomatic or mildly symptomatic workers, suggesting that work activities can continue if adequate infection control measures are used during a second wave.

What are the risk factors for admission to the pediatric intensive unit among pediatric patients with COVID-19?

BACKGROUND: Although with exceptions, evidence seems to indicate that children have lower susceptibility than adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When infected, children generally remain asymptomatic or develop mild disease. A small number of pediatric cases required admission to the pediatric intensive care unit (PICU), respiratory support with a mechanical ventilation and additional life-saving interventions. Even if rarely, death can occur. Aim of this manuscript is to highlight the risk factors associated with severe outcome among pediatric patients with COVID-19. MAIN FINDINGS: Early identification of SARS-CoV-2-infected children at risk of developing severe COVID-19 is vital for service planning, as severely affected pediatric patients require high-quality care and should be followed only where an adequately structured PICU is available. However, early identification of children who must be carefully monitored for substantial risk of severe COVID-19 remains difficult. An underlying comorbidity and heart involvement are frequently observed in severe paediatric cases. Reduced left ventricular systolic function with an ejection fraction < 60%; diastolic dysfunction; and arrhythmias, including ST segment changes, QTc prolongation, and premature atrial or ventricular beat, are the earliest manifestations of heart involvement. Inclusion of heart enzyme serum levels and evaluation of ventricular function among predictive markers could lead to a more effective evaluation of children at risk with proper selection of those to admit to the PICU and with more adequate treatment in case of more severe clinical manifestations. CONCLUSIONS: To appropriately manage severe pediatric COVID-19 cases, greater attention should be paid to risk factors in children and adolescents, especially to cardiovascular alterations (e.g., heart enzyme serum levels and evaluation of ventricular function). Further studies are needed and the development of a validated score based on all the most common presumed markers of disease severity seems essential.

Coronavirus Disease-19: An Interim Evidence Synthesis of the World Association for Infectious Diseases and Immunological Disorders (Waidid).

Coronavirus disease 2019 (COVID-19) is a rapidly evolving, highly transmissible, and potentially lethal pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 11 2020, more than 7,000,000 COVID-19 cases have been reported worldwide, and more than 400,000 patients have died, affecting at least 188 countries. While literature on the disease is rapidly accumulating, an integrated, multinational perspective on clinical manifestations, immunological effects, diagnosis, prevention, and treatment of COVID-19 can be of global benefit. We aimed to synthesize the most relevant literature and experiences in different parts of the world through our global consortium of experts to provide a consensus-based document at this early stage of the pandemic.

Development of Psychological Problems Among Adolescents During School Closures Because of the COVID-19 Lockdown Phase in Italy: A Cross-Sectional Survey.

Background: Previous studies have shown that during COVID-19 pandemic, mainly due to the imposed lockdown, significant psychological problems had emerged in a significant part of the population, including older children and adolescents. School closure, leading to significant social isolation, was considered one of the most important reasons for pediatric mental health problems. However, how knowledge of COVID-19 related problems, modification of lifestyle and age, gender and severity of COVID-19 pandemic had influenced psychological problems of older children and adolescents has not been detailed. To evaluate these variables, a survey was carried out in Italy. Methods: This cross-sectional survey was carried out by means of an anonymous online questionnaire administered to 2,996 students of secondary and high schools living in Italian Regions with different COVID-19 epidemiology. Results: A total of 2,064 adolescent students (62.8% females; mean age, 15.4 ± 2.1 years), completed and returned the questionnaire. Most of enrolled students showed good knowledge of COVID-19-related problems. School closure was associated with significant modifications of lifestyle and the development of substantial psychological problems in all the study groups, including students living in Regions with lower COVID-19 incidence. However, in some cases, some differences, were evidenced. Sadness was significantly more frequent in females (84%) than males (68.2%; p < 0.001) and in the 14-19-year-old age group than the 11-13-year-old age group (79.2% vs. 70.2%; p < 0.001). Missing the school community was a significantly more common cause of sadness in girls (26.5% vs. 16.8%; p < 0.001), in southern Italy (26.45% vs. 20.2%; p < 0.01) and in the 14-19-year-old group (24.2% vs. 14.7%; p < 0.001). The multivariate regression analysis showed that male gender was a protective factor against negative feelings (p < 0.01), leading to a decrease of 0.63 points in the total negative feelings index. Having a family member or an acquaintance with COVID-19 increased the negative feelings index by 0.1 points (p < 0.05). Conclusions: This study shows that school closures because of the COVID-19 pandemic outbreak was associated with significant lifestyle changes in all the students, regardless of age and gender. Despite some differences in some subgroups, the study confirms that school closure can cause relevant mental health problems in older children and adolescents. This must be considered as a reason for the maintenance of all school activities, although in full compliance with the measures to contain the spread of the pandemic.

Why It Is Important to Develop an Effective and Safe Pediatric COVID-19 Vaccine.

The need to cope with the medical, social, and economic storm due to the new coronavirus 2019 (COVID-19) pandemic as quickly as possible has led to the very rapid development of a huge number of vaccines. All these vaccines have been mainly developed in healthy adults and, in some cases, in the elderly. Children were marginally involved as, according to the clinical trial registry Clinical Trials.gov, only very few studies have included children among subjects to enroll, although just a few weeks after the pandemic declaration, the US Food and Drug Administration had highlighted the importance of vaccine evaluation in pediatrics. Availability of an effective and safe pediatric COVID-19 vaccine appears mandatory for several clinical and epidemiological reasons. However, as the development of an effective and safe pediatric vaccine seems far from easy, strong cooperation among governments, researchers, and pharmaceutical companies is highly desirable.