Acute severe hepatitis outbreak in children: a perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future

Optional Vaccines in Children—Knowledge, Attitudes, and Practices in Romanian Parents

Vaccination is one of the most useful medical interventions for controlling certain infectious diseases. The aim of current research is to identify some of the drivers of vaccine hesitancy or acceptance in a rather skeptical European population by addressing parental perception on optional vaccination (OV) perception. Novel tools, delivered by social media, were used in our research attempt. A validated questionnaire was distributed online among parents. Parental knowledge, attitudes and perceptions of OV were analyzed. The majority of parent respondents (55.1%) showed very good knowledge about vaccination and vaccine-preventable diseases, and 76.0% stated that they had given at least one optional vaccine to at least one of their children. The most common optional vaccine administered was the rotavirus vaccine. The level of knowledge appeared to be related to compliance with OV. Concurrently, the rate of vaccine acceptance in the NIP (National Immunization Program) was not correlated with the level of parental knowledge. In total, a high percentage of parents (77.6%) believed that OV can bring an additional health safety benefit to their children. This study shows the need to involve the medical community in a steady dialogue with parents about OV. Raising awareness by presenting clear and understandable information could be a game-changing intervention in mitigating the public health impact of OV-preventable diseases

Pediatric Emergencies and Hospital Admissions in the First Six Months of the COVID-19 Pandemic in a Tertiary Children’s Hospital in Romania

The COVID-19 pandemic has had a significant impact on the pediatric population, particularly on their access to health services. We conducted a retrospective study to assess the influence that the pandemic, and its related containment and mitigation public health measures, had on pediatric emergencies and hospitalizations in a major tertiary pediatric hospital in Bucharest, Romania, during the first six months of the pandemic, March–August 2020, compared to the same period in 2019. In these first 6 months of the COVID-19 pandemic, the number of pediatric emergencies decreased 2.8-fold compared to the same period in 2019, but the proportion of major emergencies increased significantly (p < 0.001). The number of admissions also decreased 3.3-fold in 2020, compared to 2019, but the risk of admission for lower respiratory tract infections and respiratory failure increased 1.3- and 2.3-fold, respectively. In conclusion, the restrictions imposed by the pandemic containment and mitigation plan not only had a significant impact on reducing emergency department presentations, but also on pediatric admissions in Romania. These data highlight the importance of maintaining optimal access to child health services when confronted with a public health threat, such as the COVID-19 pandemic. Active communication with parents, involving general practitioners, pediatricians, and authorities, is essential for managing children with acute signs of illness in the case of future restrictions or lockdown measures

From COVID-19 to Influenza—Real-Life Clinical Practice in a Pediatric Hospital

The COVID-19 pandemic, through the restrictions and the non-pharmaceutical interventions implemented, has importantly impacted the circulation and epidemiology of respiratory viruses. Specifically, the 2020/21 season was entirely dominated by SARS-CoV-2, while influenza activity reached an all-time low, despite initial warnings that a double concurrent epidemic could be possible. The current season, 2021/22, started with the shift of circulating SARS-CoV-2 variants from delta to omicron, which then rapidly spread globally, as most countries, including Romania, removed all restrictions and compulsory non-pharmaceutical interventions. In this report we present the clinical reality observed in March 2022 in a tertiary paediatric hospital in Bucharest, Romania, where we observed a sudden surge in influenza cases, after two consecutive years (March 2020 to March 2022) when influenza had stopped circulating in our country. Thus, in March 2022 the positivity rate of rapid influenza antigen tests unexpectedly increased to 33.5%, paralleled by a decrease to 7.5% in the positivity rate of rapid SARS-CoV-2 antigen tests. This significant increase in the influenza attack rate was observed from the first week (14.9% positivity rate), through the fourth week of March (42.1% positivity rate, p < 0.001), while the COVID-19 attack rate displayed a significant decreasing trend (from 11.2% to 4.8%, p < 0.001). These data serve as a warning about relaxing restrictions in a precipitous approach with minimised vigilance. The evolution of these observations needs to be followed very carefully in all countries, particularly in settings where epidemiological interactions and non-pharmaceutical interventions have so far led to the extensive circulation of only one of these viruses, and we should now be prepared to perform a correct differential diagnosis between influenza and COVID-19, in order to ensure the best quality of care and personalized management of each case of respiratory infection. The results of active influenza surveillance studies for the whole 2021/22 season are awaited, in order to quantify the joint influenza—COVID-19 burden among children

Pediatric Emergencies and Hospital Admissions in the First Six Months of the COVID-19 Pandemic in a Tertiary Children’s Hospital in Romania

The COVID-19 pandemic has had a significant impact on the pediatric population, particularly on their access to health services. We conducted a retrospective study to assess the influence that the pandemic, and its related containment and mitigation public health measures, had on pediatric emergencies and hospitalizations in a major tertiary pediatric hospital in Bucharest, Romania, during the first six months of the pandemic, March–August 2020, compared to the same period in 2019. In these first 6 months of the COVID-19 pandemic, the number of pediatric emergencies decreased 2.8-fold compared to the same period in 2019, but the proportion of major emergencies increased significantly (p < 0.001). The number of admissions also decreased 3.3-fold in 2020, compared to 2019, but the risk of admission for lower respiratory tract infections and respiratory failure increased 1.3- and 2.3-fold, respectively. In conclusion, the restrictions imposed by the pandemic containment and mitigation plan not only had a significant impact on reducing emergency department presentations, but also on pediatric admissions in Romania. These data highlight the importance of maintaining optimal access to child health services when confronted with a public health threat, such as the COVID-19 pandemic. Active communication with parents, involving general practitioners, pediatricians, and authorities, is essential for managing children with acute signs of illness in the case of future restrictions or lockdown measures

Laboratory Findings in Children with Excess Body Weight in Romania

Background and Objectives: Childhood obesity has been increasing at a worrisome pace and emerging as a non-infectious pandemic in the pediatric population in recent years. Raising awareness on this problem is of utmost importance, in order to take action to control body weight from an early age. Materials and Methods: We performed a retrospective study among overweight or obese children evaluated on an outpatient basis in the Department of Pediatric Endocrinology of a tertiary care hospital in Bucharest Romania in 2021 in order to identify laboratory changes occurring according to age and sex. Results: A total of 268 children were included in the analysis, with a median age of 10.9 years (IQR: 8.3, 13.3 years); 61.8% were obese and 38.2% overweight. We identified a subclinical pro-inflammatory status characterized by increased neutrophil count (12.7%) and increased C-reactive protein (16.4%). Biochemically, we identified the highest increases for uric acid (35.4%). More than half of the children included in the study had dyslipidemia-specific changes: high low-density lipoprotein cholesterol (LDL) (50.0%), low high-density lipoprotein cholesterol (HDL) (58.9%) and increased triglyceride levels (12.7%), especially children with a body mass-index (BMI) percentile above 95%. Increased thyroid stimulating hormone (TSH) was identified in 20.3% and low thyroxine (T4) level in 13.4%, especially in females. Conclusions: Early measures to control excess body weight are needed since preventing obesity is easier than treating it. However, this is often difficult to do in our country because parents frequently do not recognize the problem until it is advanced. Furthermore, doctors are not always adequately prepared and sometimes they do not have the support of the health systems to provide children in need with the adequate care. Educational strategies and awareness of issue should be revisited in current post-pandemic context that facilitates increase of obesity prevalence in children. Increase of efficient communication could be achieved by pointing to these objective findings

Laboratory Findings in Children with Excess Body Weight in Romania

Background and Objectives: Childhood obesity has been increasing at a worrisome pace and emerging as a non-infectious pandemic in the pediatric population in recent years. Raising awareness on this problem is of utmost importance, in order to take action to control body weight from an early age. Materials and Methods: We performed a retrospective study among overweight or obese children evaluated on an outpatient basis in the Department of Pediatric Endocrinology of a tertiary care hospital in Bucharest Romania in 2021 in order to identify laboratory changes occurring according to age and sex. Results: A total of 268 children were included in the analysis, with a median age of 10.9 years (IQR: 8.3, 13.3 years); 61.8% were obese and 38.2% overweight. We identified a subclinical pro-inflammatory status characterized by increased neutrophil count (12.7%) and increased C-reactive protein (16.4%). Biochemically, we identified the highest increases for uric acid (35.4%). More than half of the children included in the study had dyslipidemia-specific changes: high low-density lipoprotein cholesterol (LDL) (50.0%), low high-density lipoprotein cholesterol (HDL) (58.9%) and increased triglyceride levels (12.7%), especially children with a body mass-index (BMI) percentile above 95%. Increased thyroid stimulating hormone (TSH) was identified in 20.3% and low thyroxine (T4) level in 13.4%, especially in females. Conclusions: Early measures to control excess body weight are needed since preventing obesity is easier than treating it. However, this is often difficult to do in our country because parents frequently do not recognize the problem until it is advanced. Furthermore, doctors are not always adequately prepared and sometimes they do not have the support of the health systems to provide children in need with the adequate care. Educational strategies and awareness of issue should be revisited in current post-pandemic context that facilitates increase of obesity prevalence in children. Increase of efficient communication could be achieved by pointing to these objective findings

Optional Vaccines in Children—Knowledge, Attitudes, and Practices in Romanian Parents

Vaccination is one of the most useful medical interventions for controlling certain infectious diseases. The aim of current research is to identify some of the drivers of vaccine hesitancy or acceptance in a rather skeptical European population by addressing parental perception on optional vaccination (OV) perception. Novel tools, delivered by social media, were used in our research attempt. A validated questionnaire was distributed online among parents. Parental knowledge, attitudes and perceptions of OV were analyzed. The majority of parent respondents (55.1%) showed very good knowledge about vaccination and vaccine-preventable diseases, and 76.0% stated that they had given at least one optional vaccine to at least one of their children. The most common optional vaccine administered was the rotavirus vaccine. The level of knowledge appeared to be related to compliance with OV. Concurrently, the rate of vaccine acceptance in the NIP (National Immunization Program) was not correlated with the level of parental knowledge. In total, a high percentage of parents (77.6%) believed that OV can bring an additional health safety benefit to their children. This study shows the need to involve the medical community in a steady dialogue with parents about OV. Raising awareness by presenting clear and understandable information could be a game-changing intervention in mitigating the public health impact of OV-preventable diseases

Liver Transaminases in Pediatric Adenovirus Infection—A Five-Year Study in Two Major Reference Centers from Romania

Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein–Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients

Liver Transaminases in Pediatric Adenovirus Infection&mdash;A Five-Year Study in Two Major Reference Centers from Romania

Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein&ndash;Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients