Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.

Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.

Cytomegalovirus (CMV) is the most common cause of congenital infection and non-genetic sensorineural hearing loss in childhood. Up to 2% of neonates, with the highest percentages found in developing countries, are congenitally infected with CMV. At birth, most of these infants are asymptomatic. However, approximately 10% have signs and symptoms of the disease, and 40–60% of symptomatic neonates will later develop permanent neurologic sequelae. To reduce congenital CMV (cCMV) infection, a vaccine able to prevent primary infection is essential. In this narrative review, actual ongoing research about the development of a CMV vaccine is discussed. The progressive increase in knowledge on the ways in which the host’s immune system and CMV relate has made it possible to clarify that the development of a vaccine that is certainly capable of reducing the risk of cCMV infection, and preventing both primary and nonprimary infections is extremely difficult. Many of the ways in which the virus evades the immune system and causes cCMV infection are not yet fully understood, especially in cases of nonprimary infection. Moreover, the schedule that should be recommended and that subjects must be vaccinated to obtain the greatest effect have not been precisely defined. Further studies are needed before the problem of cCMV infection and its related challenges can be totally solved.

Sickle cell disease (SCD) is the most common genetic disease in sub-Saharan Africa. The signs and symptoms of SCD usually begin in early childhood. Characteristic features of this disorder include anaemia, repeated infections, and periodic episodes of pain. Malaria is one of the infections that can occur in patients with SCD in endemic countries. Many guidelines recommend antimalarial chemoprophylaxis in these patients, although the debate on which drug should be used is still ongoing. Hydroxyurea (HU), which is considered a safe and effective treatment for both children and adults with SCD, seems to affect the incidence and severity of malaria, although these impacts have yet to be fully demonstrated. We report a case of an eight-and-a-half-year-old Sudanese boy with SCD treated with HU admitted for suspected severe malaria who showed a recrudescence after first-line treatment. Although he had undergone splenectomy and thus belonged to a category of patients at high risk for infectious complications, he was not receiving any malaria chemoprophylaxis. This case emphasises the importance of the routine administration of malaria prophylaxis to children with SCD living in endemic areas, even when they are treated with HU, and especially if they are at high risk for infectious complications because they have undergone splenectomy. There is an urgent need for further research to evaluate the most appropriate regimen and its optimal duration.

Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1–3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases.