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.

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.

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.

Omicron in Infants-Respiratory or Digestive Disease?

The Omicron variant of SARS-CoV-2 has caused a large number of cases and hospitalizations in the pediatric population. Infants due to their age are susceptible to viral infections that may have a worse prognosis. Therefore, the aim of the current study has been to characterize the clinical features and the outcome of infants hospitalized with confirmed SARS-CoV-2 infection during the Omicron wave. We conducted a retrospective study of all consecutive infants hospitalized with symptomatic COVID-19 and no other co-infections, from January to September 2022 in one of the largest infectious diseases hospitals from Bucharest, Romania. A total of 613 infants were included in the analysis. The median age was 5 months (IQR: 3, 8 months). The clinical features were dominated by fever (96.4%), cough (64.8%) and loss of appetite (63.3%), and overall, respiratory symptoms were the most numerous (76.0%). Infants between 1-3 months old had a 1.5-fold increased risk of elevated alanine aminotransferase (ALT) values, and a longer length of hospitalization as compared to older infants. Infants between 7-9 months of age had 1.5-fold higher odds of loss of appetite, 1.7-fold more frequent cough and 1.6-fold more frequent digestive symptoms compared to infants in other age groups. The presence of digestive symptoms increased the probability of hepatic cytolysis (increased ALT) by 1.9-fold. Continued monitoring of COVID-19 among infants is very necessary, given the progressive character of SARS-CoV-2, in order to take correct and rapid therapeutic measures and to adapt to clinical changes driven by viral variant change.

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.

Prevalence of undiagnosed hepatitis B virus infection in patients with COVID-19A single center retrospective study.

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.

Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection-A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center.

During the current pandemic, the gap between fundamental research and clinical practice has been narrowing at a faster pace than ever before. While clinical trials play the main role of confirming the safety and efficacy of new drugs, a drug's introduction into clinical practice creates the need for further research in order to best position the use of the novel drug in terms of when, to whom, and how it would be best administered to achieve the best possible outcome under feasible clinical circumstances. We briefly present the results of a retrospective analysis of the characteristics of outpatients treated with molnupiravir in a tertiary care infectious disease hospital in Bucharest, Romania, between February and March 2022, when Romania was experiencing its fifth wave of COVID-19. A total of 46 outpatients received molnupiravir treatment and had complete clinical data available; of them, 56.5% (n = 20) were males and the median age was 48.5 years (IQR: 37.8, 67.0 years). A total of 54.2% (n = 26) of patients had at least one chronic condition. Of the 45 patients who underwent lung CT imaging evaluation, 13 (28.9%) showed changes suggestive of COVID-19 pneumonia. COVID-19 vaccination status was strongly protective for pneumonia (p = 0.002). All patients were symptomatic, and molnupiravir was initiated at a mean time from onset of symptoms of 3.5 (±1.5) days. At phone follow-up 5 days after the initial evaluation and initiation of molnupiravir treatment, all patients, except for one, confirmed a favorable course under treatment, with no worsening of COVID-19 severity and improvement in symptoms; none of them progressed to respiratory failure or required hospitalization. In conclusion, treatment was well tolerated and associated a favorable outcome of COVID-19 in routine practice in a clinical population that was slightly older and had a smaller burden of comorbidities and a higher rate of COVID-19 vaccination compared to that from the pivotal trial.

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.

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.

Undetected Omicron Transmission in Romania-Report of the First Detected Case of Locally Acquired Omicron Infection and Complete Epidemiological Investigation.

The occurrence of the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has importantly impacted surveillance and diagnosis, and has changed the therapeutic landscape of coronavirus disease 2019 (COVID-19). We present the first documented case of locally acquired SARS-CoV-2 omicron variant in Romania in a patient with no recent travel outside the country. We also present the full results of the epidemiological investigation that led to the identification of the index case in a co-worker who had developed mild symptoms shortly after returning from the UK and who had undergone multiple rapid antigen tests with negative results prior to being tested by RT-PCR. We highlight potential lessons learned and describe further directions for actionable research and development in the field of COVID-19.

Comparative Analysis of Clinical and Epidemiological Characteristics in Patients with SARI Confirmed as Influenza or COVID-19 Admitted in a Tertiary Care Hospital in Bucharest, Romania

The COVID-19 pandemic has influenced the epidemiology of other respiratory pathogens, and this was most evident in the 2020–2021 season, which was characterized by a low circulation of influenza viruses. We aim to present a comparative analysis of clinical and epidemiological characteristics of 2018–2019 influenza cases and 2020–2021 COVID-19 cases, hospitalized at a tertiary infectious diseases hospital in Bucharest. We used data collected from patients admitted for severe acute respiratory infection (SARI) and subsequently confirmed with either influenza or COVID-19. During the 2018–2019 season, 208 patients over 18 years of age were confirmed with influenza (median age = 53 years, 59.6% were female) and 6.7% had been vaccinated against influenza. The most frequent symptoms were fever (97.1%) and cough (94.7%), and 77.4% had at least one chronic condition. 90.4% received influenza antiviral therapy. During the 2020–2021 season, 191 patients were confirmed with COVID-19 (median age = 56 years, 67% were male). The most frequent symptoms were cough (85.9%) and fever (80.6%), and 75.9% had at least one chronic condition. This analysis highlights the main similarities and differences between influenza and COVID-19 and could help to optimize the management of cases.

First Case of COVID-19 Treated with Monoclonal Anti-Spike Antibodies in a Patient with Cystic Fibrosis in Romania.

Patients with chronic lung conditions, including cystic fibrosis, may be prone to severe COVID-19. Therefore, therapeutic intervention should be prompt and tailored to all associated comorbidities. We report the case of a 17-year-old male adolescent with cystic fibrosis and multiple chronic conditions (bronchiectasis, exocrine pancreatic insufficiency, chronic multidrug resistant Pseudomonas aeruginosa colonization, nasal polyposis, chronic sinusitis, ventricular extrasystoles and multiple drug allergies), who presented with an acute episode of productive cough, and was confirmed with moderate COVID-19 based on positive RT-PCR for SARS-CoV-2 and lung imaging showing isolated foci of interstitial pneumonia. Intravenous treatment with the monoclonal antibody cocktail casirivimab and imdevimab was administered. The evolution was favorable, with rapid remission of the inflammatory syndrome and gradual decrease of cough, without progression to severe or critical COVID-19, but with complications such as repeated hemoptysis, which was due to the patient's underlying conditions, and which required close monitoring for timely adjustment of the patient's chronic treatment.

Comprehensive Overview of Vaccination during Pregnancy in Europe.

Vaccinations during pregnancy can protect the mother from several infections, thus blocking vertical transmission. Furthermore, through passive antibody transfer, the newborn can be protected against some infections in the first months of life until their own vaccination regimen is initiated and completed at the appropriate age. Pregnancy can be considered a high-risk condition that increases vulnerability to infectious diseases with potentially unfavorable evolution. We present the current knowledge on vaccination during pregnancy in Europe as a useful information source for different health workers involved in prenatal care. Many European countries implement vaccination policies specifically designed for pregnant women, but there is great heterogeneity among programs. Recommendations on vaccination during pregnancy must be based on current high-quality scientific data. The decisions must be made for each individual case, depending on the associated conditions or special circumstances, with a concomitant assessment of the potential benefits and risks to both the pregnant patient and the fetus. Many vaccines are well-tolerated in pregnant women, with no clinically meaningful injection site reactions, systemic symptoms, or vaccine-related serious adverse events.

"Red throat" or acute pharyngitis – challenges in real life clinical practice

An interesting article by Oksana Boyarchuk et al. has just been published in the current issue of Germs - "Diagnosis and management of pharyngitis in children: a survey study in Ukraine".1 This study evaluated "the knowledge of pediatricians in diagnosis and management of sore throat in children" and the results showed "low knowledge about the diagnosis and determination of strategies in healthy carriers".1 The question we should ask when confronted with these results is whether this situation is isolated or is it common among doctors in other countries as well? Oropharyngeal changes highly suggestive of streptococcal infection (Figure 1) are not seen in all GAS positive cases. [...]it should be kept in mind that the likelihood of GAS is inversely proportional to the number of viral features (cough, coryza, rhinorrhea, ulcers/vesicles, conjunctival injection).4 Moreover, the modified Centor score (McIsaac)5 or feverPAIN score6 seem to be useful tools in identifying those at increased likelihood of GAS. A growing number of reports show increasing resistance to macrolides: from 34.4% in Japan9 and 40% in Bulgaria10 to 93.5% in China.11 There is also evidence showing resistance to quinolones12 or even beta-lactams.13 A diagnosis that may seem easy to provide can be a major challenge for the clinician, especially in the current pandemic when parental attitudes toward the child with acute signs of illness have changed.14 The history and full clinical examination play an important role in guiding the therapeutic measures we take.