COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

The diversity in the clinical features of children hospitalized with COVID-19 during the nonvariant, Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) variant periods of SARS CoV-2: Caution for neurological symptoms in Omicron variant.

Since the COVID-19 pandemic began, various severe acute respiratory syndrome coronavirus 2 variants have been identified with different characteristics than the nonvariant strain. We retrospectively evaluated the demographic and clinical differences in the cohort of hospitalized COVID-19 children (1 month-18 years old) between March 11, 2020, and September 31, 2022, by the time the variants identified in our country predominate. Bonferroni post hoc analysis was performed to compare the differences between the periods. Of the 283 children in this study, 142 (50.2%) were females. The median age was 36 (interquartile range [IQR]: 7-132) months. Sixty-three (22.2%) patients were hospitalized in the nonvariant period, 24 (8.5%) in the Alpha period, 93 (32.9%) in the Delta period, and 103 (36.4%) in the Omicron period. Fever was the most common symptom in all groups, with no statistically significant differences (p = 0.25). In the Omicron period, respiratory and gastrointestinal symptoms decreased, and neurological symptoms increased significantly compared to other periods: [respiratory symptoms; nonvariant (65.1%) vs. Omicron (41.7%), (p = 0.024)], [gastrointestinal symptoms; Delta (41.9%) vs. Omicron (22.3%), (p = 0.018), [neurological symptoms; Delta (14.5%) vs. Omicron (31.1%), (p = 0.03]. Altered mental status and seizures were more common during the Omicron period compared to the pre-Omicron (nonvariant, Alpha, and Delta) period (p = 0.017 and p = 0.005, respectively). Although the main symptoms in children with COVID-19 were fever and respiratory symptoms, an increase in severe neurological manifestations was seen throughout the Omicron variant period.

Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children.

BACKGROUND: Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. METHODS AND RESULTS: Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the - 221nt and - 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). CONCLUSION: These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19.

Diagnostic Accuracy of SARS-CoV-2 Rapid Antigen Testing in a Pediatric Population: Children are Not Little Adults.

BACKGROUND: Information on the use of antigen-based SARS-CoV-2 rapid antigen tests (RAT) in children is limited. RATs have been used more frequently, because they are easily applicable, inexpensive, and can be easily performed at home without the need for special equipment. This study was designed to assign the diagnostic test accuracy of the SARS-CoV-2 RAT in daily clinical practice in children. METHODS: One thousand forty-two pediatric patients (aged 1 month - 18 years) who presented to the pediatric COVID-19 outpatient clinic of our hospital between January 2021 and June 2022 and met the inclusion criteria were included in this study. Nasopharyngeal samples were taken from the patients at the same visit, first for reverse transcription polymerase chain reaction (RT-PCR) and then for RAT. RESULTS: The data of all patients with RT-PCR positivity (n = 314) and additionally 14 patients with RAT positivity were analyzed in depth. The overall sensitivity and specificity were 62.1% (95% CI: 56.4 - 67.4) and 98% (95% CI: 96.7 - 98.9), respectively. The positive predictive value (PPV) and the negative predictive value (NPV) in this pediatric study were 93.3% and 85.7% (95% CI: 88.7 - 96.1 and 83.1 - 87.9), respectively. Considering the Ct values, which are indirect indicators of viral load, it was observed that the sensitivity of the rapid antigen test increased at low Ct values. The sensitivity increased to 75.1% (95% CI: 67.9 - 81.1) in patients with a Ct value of < 25. The specificity was 92.7% (95% CI: 90.7 - 94.3), PPV was 67.8% (95% CI: 60.7 - 67.8) and the NPV was 94.7% (95% CI: 93.0 - 96.1) in patients with a Ct value < 25. When the patients were evaluated according to their symptomatic/asymptomatic status, the difference between the diagnostic performance of the RAT test was found to be statistically significant (p = 0.006). CONCLUSIONS: In our study, it was found that the sensitivity of RATs in pediatric patients was lower than in adults. Our results also showed that children are not small adults, and the sensitivity of the test was higher, especially in symptomatic patients and patients with high viral load. To obtain more accurate results, we believe that performing the test in the first 3 days of symptoms will give more accurate results.

Parental Attitudes About Lumbar Puncture in Children With Suspected Central Nervous System Infection.

OBJECTIVES: This study aimed to evaluate parents' attitudes toward lumbar puncture (LP) for their children with suspected central nervous system infection to determine the reasons for rejection and related factors. METHODS: The survey was provided to parents of children (1 month to 18 years old) for whom LP was recommended because of a concern for central nervous system infection. Sociodemographic characteristics and other related factors of parents who did and did not approve of LP were compared statistically. The reasons for the disapproval of parents who refused LP were revealed. RESULTS: A total of 100 parents were included in the study. Eighty-two percent of the participating parents were mothers, and the median age of the mothers was 31 years (min: 17 years; max: 70 years). The median age of the fathers was 37 years (min: 22 years; max: 60 years). Among the parents, 34% did not give consent for LP. The most common reason for the participants to refuse LP was fear of paralysis of their children due to the procedure (82.3%). There was a statistical difference between the approval of the LP procedure and the person who informed the parents about the LP procedure and read the informed consent form ( P = 0.004 and P = 0.038, respectively).As a result of the binary logistic regression analysis, it was seen that the rate of acceptance of the LP procedure by the parents informed by the specialist doctors was 7.1-fold ( P = 0.02; 95% confidence interval, 1.3-37.6) higher than the parents informed by the resident physicians. CONCLUSION: The informed consent process mainly influenced parents' attitudes toward LP. To increase the acceptance rates of LP, we should standardize the informed consent process so that it is not affected by factors such as seniority of the physician.

[An Infant with Zoonotic Pulmonary Tuberculosis due to Mycobacterium bovis]. / Mycobacterium bovis'e Bagli Zoonotik Pulmoner Tüberküloz Tanili Bir Infant.

Bovine tuberculosis might be seen in low-income countries, especially in children fed with raw milk. The most common transmission route is fecal-oral way, and it is most likely through unpasteurized dairy products. Although clinical and radiological findings are like non-zoonotic tuberculosis, treatment approaches may differ in individuals with zoonotic tuberculosis. Prevention of zoonotic diseases requires multidisciplinary approaches. These approaches include the development of veterinary and surveillance studies for the detection of communicable diseases in farm animals, as well as informing the public about raw milk consumption. In this case report, a patient with zoonotic pulmonary tuberculosis related to Mycobacterium bovis because of consumption of raw milk was presented. A five-month-old male was admitted to the hospital due to a persistent, feverless, non-productive cough since birth. Empirical antibiotic treatment was started with a preliminary diagnosis of pneumonia because of left upper lobe and right pericardial infiltration on chest X-ray. However, after two weeks of antimicrobial therapy, the patient's clinical and laboratory findings did not improve. This led to the referral for a computed tomography imaging, which revealed tracheomalacia, consolidation on the right upper lobe, an indistinguishable mass or consolidation on the left middle lobe of the lung, peribronchial thickening on the basal segment of the lower lobe, and mediastinal lymphadenopathy. Three consecutive days of fasting gastric lavage fluid was sent to the reference laboratory for acid-resistant bacillus examination, polymerase chain reaction (PCR) and culture studies. As the clinical findings were compatible and PCR was positive, the patient was started on quadruple antituberculous therapy. After initiation of anti-tuberculosis drugs, the patient's findings radiologically and clinically were improved. Mycobacterium bovis was grown in the culture. In the meantime, it was discovered that the patient was fed with raw milk. Due to the patient's clinical symptoms and the growth of Mycobacterium bovis in the gastric lavage fluid culture, the diagnosis of bovine tuberculosis was made. The culprit was that the milk of the cow belonging to the patient's family, which was later found to be infected with M.bovis, was milked and given to the patient without boiling. Today, unpasteurized dairy products continue to be consumed, especially in rural areas. One of the most important steps to prevent zoonotic diseases is to raise awareness about not consuming raw milk and undercooked meat. To elucidate the epidemiological link in childhood, taking a good anamnesis, including questioning raw milk consumption, is essential in the diagnosis of tuberculosis.

Influenza is more severe than our newest enemy (COVID-19) in hospitalized children: Experience from a tertiary center.

Understanding differences in terms of clinical phenotypes and outcomes of coronavirus disease 2019 (COVID-19) compared with influenza is vital to optimizing the management of patients and planning healthcare. Herein, we aimed to investigate the clinical differences and outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza. We performed a retrospective study of hospitalized children who were positive for SARS-CoV-2 between March 2020 and March 2021 and for influenza between January 2016 and February 2020 in respiratory samples. The primary outcome of this study was pediatric intensive care unit (PICU) admission, and the secondary outcome was the need for respiratory support. A total of 74 patients with influenza and 71 who were positive for SARS-CoV-2 were included. The distribution among the sexes was similar, but patients with COVID-19 were older than patients with influenza (96 vs. 12, p < 0.001). In terms of underlying chronic diseases, the frequency was 26.7% in the COVID-19 group and 54% in the influenza group (p = 0.001). The comparison of symptoms revealed that fatigue, headache, nausea, vomiting, and abdominal pain occurred more frequently with COVID-19 (for all p < 0.05) and runny nose with influenza (p = 0.002). The frequency of admission to the PICU was relatively higher (18.9%) in the influenza group than with COVID-19 (2.8%) with a significant ratio (p = 0.001), secondary bacterial infections were observed more frequently in the influenza group (20.2% vs. 4.2%, p = 0.003). Some 88.7% of patients with COVID-19 did not need respiratory support, whereas 59.4% of patients with influenza did require respiratory support (p < 0.001). This study noted that influenza caused more frequent admissions to the PICU and a greater need for respiratory support in hospitalized pediatric patients than COVID-19.

Serum zinc levels in pediatric patients with COVID-19.

Zinc has potent immunoregulatory and antiviral effects that are critical for growth, immunity, and neurologic development. The aim of this study was to determine the clinical significance of serum zinc levels in pediatric patients with COVID-19 and to demonstrate its association with disease severity. This prospective observational study was conducted between August 3 and November 15, 2020, in pediatric patients aged 1 month to 18 years with confirmed COVID-19 using reverse transcription-polymerase chain reaction. We defined a control group whose serum zinc levels were determined 1 year ago at the same time as those of patients with COVID-19. We used 70 µg/dL as the cut-off zinc value to define zinc deficiency. Statistical analyses were performed using the SPSS for Windows statistics package program. One hundred children with confirmed COVID-19 and 269 children in the control group participated in the study. The median age was 13.3 (IQR: 8-15.4) years in patients with confirmed COVID-19, 11 patients had low serum zinc levels, and 89 patients had normal serum zinc levels. Patients in the group with low zinc levels had a significantly higher hospitalization rate than the group with normal zinc levels (5 (45.5%) and 10 patients (11.2%), respectively) (p = 0.011). The median serum zinc level in patients with COVID-19 was 88.5 mcg/dL (IQR 77.2-100), which was significantly lower than the median level in the control group, which was 98 mcg/dL (IQR 84-111) (p = 0.001). There was no association between the severity of COVID-19 and the serum zinc levels of the children. CONCLUSION: Serum zinc levels may be influenced by many factors such as fasting status, diurnal variation, exercise, and sex, and may give an impression of the zinc status of the population rather than reflecting the individual. The fact that the incidence of hospitalization was significantly higher in patients with both COVID-19 and low serum zinc levels suggests that these patients require a detailed assessment of their living environment. WHAT IS KNOWN: • Serum zinc levels have been found to be low in adult patients diagnosed with COVID-19. • There was a correlation between the severity of COVID-19 and serum zinc levels in adults. WHAT IS NEW: • Children with low serum zinc levels were found to have a higher number of hospitalizations. • No association was found between the severity of COVID-19 disease and serum zinc levels in children.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.

Evaluation of Depression, Anxiety, and Sleep Quality in Children Diagnosed With COVID-19.

ABSTRACT: COVID-19 has affected individuals of all age groups, both physically and mentally. We aimed to determine anxiety and depression in children diagnosed with COVID-19. Fifty children aged 8 to 18 years diagnosed with COVID-19 were included in the study. The children were evaluated the revised Child Anxiety and Depression Scale, STAI form TX-I (state anxiety inventory), and STAI form TX-II (trait anxiety inventory). Child Sleep Habits Questionnaire was applied for one of the parents according to three different periods. The periods were established as before the pandemic, during the illness-quarantine process, and after the quarantine. We observed the highest scores for depression-anxiety and the poorest sleep quality during the quarantine period. The scores for depression-anxiety were lower, and sleep quality scores were higher in the prepandemic period compared with after the quarantine period. Measures should be taken to protect mental health for children with COVID-19.

Coronavirus disease 2019 in healthy children: What is the effect of household contact?

BACKGROUND: Coronavirus disease 2019 (COVID-19) in children is milder than in adults. Household virus exposure may affect clinical severity. We aimed to determine the household contact history of patients and its influence on the clinical stage. METHODS: One hundred and seventy-three pediatric patients with COVID-19 as diagnosed with positive real-time polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 aged 1 month to 18 years were included. Demographic data, laboratory and clinical findings, and the history of household contact of the patients were obtained. They were classified according to their clinical stage as mild or moderate-severe. RESULTS: Sixty patients (34.7%) were asymptomatic, and 113 were symptomatic (65.3%). Of the 173 patients, 138 (79.8%) had at least one family member in the household who was diagnosed as having COVID-19. Hemoglobin, absolute neutrophil count, and absolute neutrophil count /absolute lymphocyte count ratio decreased significantly in patients with household contact. The presence of a household contact did not have a significant effect on the presence of symptoms, clinical course, age, and the sex of the patients. The need for hospitalization was less in the group that had household contact. Being 0-12 months, being female, and being a patient without household contact were independent factors associated with higher hospitalization ratios in logistic regression analysis. CONCLUSIONS: In this study, we found that household contact history did not significantly affect presenting symptoms and clinical course. We detected the rate of hospitalization to be less in the group with only household contact.

Infant colic or early symptom of autism spectrum disorder?

BACKGROUND: Gastrointestinal (GI) disorders are common in autism spectrum disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not been evaluated in this patient group. The aim of this study was therefore to determine the rate of IC in ASD and investigate a possible association between ASD and IC. METHODS: The subjects consisted of 100 ASD patients (mean age, 6.6 ± 3.5 years) and 100 healthy controls (mean age, 5.3 ± 2.8 years). The parents were questioned using the diagnostic criteria for infant colic for clinical research purposes defined in Rome IV to diagnose IC, retrospectively. The sample size was estimated using a maximum type I error probability of 5% (alpha) and a type II error of 20%. RESULTS: The rate of IC was 16% and 17% in the ASD group and control group, respectively (P ˃ 0.05). Excessive crying with late onset and long duration in infants was defined as persistent crying. The rate of persistent crying was significantly higher in the ASD group than in the control group (32% vs 9%, P < 0.001). The relative risk of persistent crying was 4.40 in ASD. The likelihood of being misdiagnosed with IC in this group was 78%. CONCLUSION: The rate of IC is not increased in patients with ASD, but infants with excessive crying should be very thoroughly evaluated before being diagnosed with IC. In particular, persistent crying in infants (i.e. excessive crying with late onset and long duration) may be an early symptom of ASD.

Clinical Reflections of Acinetobacter Infections in Children in a Quaternary-Care Hospital: A Five-Year Single-Center Experience.

OBJECTIVE: This study aimed to determine the epidemiology of Acinetobacter species in the last 5 years, the clinical diseases caused by the pathogen, the possible risk factors for infection, and the resistance pattern of the microorganism in our quaternary-care hospital. MATERIALS AND METHODS: In this retrospective cohort study, 67 pediatric cases infected with Acinetobacter species in our hospital between January 2017 and December 2021 were analyzed. Demographic characteristics and clinical and laboratory findings were analyzed. RESULTS: In pediatric patients infected with Acinetobacter spp., the median age was 36 (7-114) months, and 64.2% (n = 43) were female. Acinetobacter baumannii was grown in the cultures of 31 (46.3%) cases. When the type of infection was examined, 31 (46.3%) cases were urinary tract infections, and 29 (43.3%) cases were bloodstream infections. Extensively drug-resistant, pandrug-resistant, and multidrug-resistant A. baumannii were found in 10 (14.9%), 3 (4.5%), and 2 (3%) cases, respectively. Health-care-associated infections were found to have a significant rate of Acinetobacter resistance (P = .002). Significant antimicrobial resistance was detected in Acinetobacter-infected cases with intensive care hospitalization within the last month and carbapenem use in the previous 3 months (P < .001, both). CONCLUSION: It is necessary to act in accordance with the infection prevention and control program to reduce the incidence of health-care-associated infections with Acinetobacter species and to prevent infection with highly resistant strains. Due to health-care-associated infections and factors contributing to the increase in Acinetobacter resistance, we believe this study will help clinicians to be more cautious in the use of carbapenems. Cite this article as: Elvan-Tüz A, Tekin D, Ekemen-Keles Y, et al. Clinical reflections of acinetobacter infections in children in a quaternary-care hospital: A five-year single-center experience. Turk Arch Pediatr. 2024;59(1):38-42.

A prospective long-term evaluation of the ocular findings of children followed with the diagnosis of multisystem inflammatory syndrome (long-term evaluation of ocular findings following MIS-C).

BACKGROUND/OBJECTIVES: The most frequently reported ocular finding in the acute phase of the multisystem inflammatory syndrome in children (MIS-C), is conjunctivitis. More rarely, punctuate epitheliopathy, anterior uveitis and optic disc oedema can be seen. We aimed to investigate the acute and long-term ocular effects of MIS-C. SUBJECTS/METHODS: Cases aged 1 month to 18 years who were diagnosed with MIS-C between January 2022 and June 2022 in the Department of Pediatric Infectious Diseases in our hospital were included in the study. Ophthalmological examinations were performed immediately after diagnosis, at one month, three months, and six months. RESULTS: Males consisted of 64.7% of the 34 cases included in the study and the mean age was 8.68 ± 4.32 years (min-max:2-17). In the first examination, conjunctivitis was observed in 6 (17.6%), punctuate epitheliopathy in 4 (11.7%), and subconjunctival haemorrhage in 3 (8.8%) patients. Two patients (5.8%) had optic disc oedema. No pathological anterior or posterior segment findings were observed in the sixth-month examination. The relationship between subconjunctival haemorrhage and intensive care hospitalisation was statistically significant (p = 0.014). Also, all patients with subconjunctival haemorrhage were clinically classified as severe MIS-C (p = 0.002). CONCLUSION: Although pathological ocular findings were observed in the acute phase of the disease, all of them were found to be improved at the sixth-month follow-up. The most striking finding of our study is that cases with subconjunctival haemorrhage were clinically more severe, and all patients needed intensive care. This study may be informative in establishing ocular follow-up protocols that are expected to be carried out in the acute period and in the follow-up of these patients.

Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases.

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

Evaluation of ischemia-modified albumin in the diagnosis and the clinical severity of COVID-19 in children.

BACKGROUND: There is no specific biomarker used in the diagnosis of COVID-19 and predicting its clinical severity. This study aimed to investigate the utility of ischemia-modified albumin (IMA) in diagnosing and predicting clinical severity in children with COVID-19. METHODS: Between October 2020 and March 2021, 41 cases constituted the COVID-19 group and 41 cases constituted the healthy control group. IMA levels were measured at admission (IMA-1) and 48-72 hours (IMA- 2) in the COVID-19 group. In the control group, it was measured at admission. COVID-19 clinical severity was classified as asymptomatic infection, mild, moderate, severe, or critical disease. Patients were divided into two groups (asymptomatic/mild and moderate/severe) to evaluate IMA levels in terms of clinical severity. RESULTS: In the COVID-19 group, the mean IMA-1 level was 0.901±0.099, and the mean IMA-2 level was 0.866±0.090. The mean level of IMA-1 in the control group was 0.787±0.051. When IMA-1 levels of COVID-19 and control cases were compared, the difference was statistically significant (p < 0.001). When clinical severity and laboratory data are compared, C-reactive protein, ferritin and ischemia-modified albumin ratio (IMAR) were statistically significantly higher in moderate-severe clinical cases (p=0.034, p=0.034, p=0.037 respectively). However, IMA-1 and IMA-2 levels were similar between the groups (p=0.134, p=0.922, respectively). CONCLUSIONS: To date, no study has been conducted on IMA levels in children with COVID-19. The IMA level may be a new marker for the diagnosis of COVID-19 in children. Studies with a larger number of cases are needed to predict clinical severity.

Attitudes of parents with children aged 12-18 to COVID-19 vaccines for themselves and their children.

BACKGROUND: The incidence of vaccine hesitancy is increasing in many countries. This study aims to determine parents` attitudes and related factors regarding COVID-19 vaccine acceptance for themselves and their children aged 12-18. METHODS: A cross-sectional survey was conducted on parents between 16th November and 31st December 2021, after COVID-19 vaccines were initiated for children in Türkiye. In the survey, the sociodemographic characteristics of the parents, whether they and their children were vaccinated against COVID-19, and if not, the reasons for this were asked. Multivariate binary logistic regression analysis was used to evaluate the factors affecting parents` refusal to vaccinate their children for COVID-19. RESULTS: Three hundred and ninety-six mothers and fathers were included in the final analysis. Overall, 41.7% of parents reported vaccine refusal for their children. COVID-19 vaccine refusal was higher in mothers younger than 35 (ß = 6.5, p = 0.002, 95% CI: 2.0-23.1), children aged 15 and younger (ß = 2.3, p = 0.001, 95% CI: 1.4-3.7). Concerns about the side effects of the COVID-19 vaccine (29.7%) and their children not wanting to be vaccinated (29.0%) were the most common causes of COVID-19 vaccine refusal. CONCLUSIONS: In the present study, the rate of children not vaccinated due to COVID-19 vaccine refusal was relatively high. Parents` concerns about vaccine side effects, as well as their children`s unwillingness to be vaccinated, suggest that both parents and adolescents should be informed about the importance of COVID-19 vaccines.

Chronic anemia is associated with systemic endothelial dysfunction.

Background: In acute myocardial infarction and heart failure, anemia is associated with adverse clinical outcomes. Endothelial dysfunction (ED) is characterized by attenuated nitric oxide (NO)-mediated relaxation responses which is poorly studied in chronic anemia (CA). We hypothesized that CA is associated with ED due to increased oxidative stress in the endothelium. Methods: CA was induced by repeated blood withdrawal in male C57BL/6J mice. Flow-Mediated Dilation (FMD) responses were assessed in CA mice using ultrasound-guided femoral transient ischemia model. Tissue organ bath was used to assess vascular responsiveness of aortic rings from CA mice, and in aortic rings incubated with red blood cells (RBCs) from anemic patients. In the aortic rings from anemic mice, the role of arginases was assessed using either an arginase inhibitor (Nor-NOHA) or genetic ablation of arginase 1 in the endothelium. Inflammatory changes in plasma of CA mice were examined by ELISA. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), myeloperoxidase (MPO), 3-Nitrotyrosine levels, and 4-Hydroxynonenal (4-HNE) were assessed either by Western blotting or immunohistochemistry. The role of reactive oxygen species (ROS) in ED was assessed in the anemic mice either supplemented with N-Acetyl cysteine (NAC) or by in vitro pharmacological inhibition of MPO. Results: The FMD responses were diminished with a correlation to the duration of anemia. Aortic rings from CA mice showed reduced NO-dependent relaxation compared to non-anemic mice. RBCs from anemic patients attenuated NO-dependent relaxation responses in murine aortic rings compared to non-anemic controls. CA results in increased plasma VCAM-1, ICAM-1 levels, and an increased iNOS expression in aortic vascular smooth muscle cells. Arginases inhibition or arginase1 deletion did not improve ED in anemic mice. Increased expression of MPO and 4-HNE observed in endothelial cells of aortic sections from CA mice. NAC supplementation or inhibition of MPO improved relaxation responses in CA mice. Conclusion: Chronic anemia is associated with progressive endothelial dysfunction evidenced by activation of the endothelium mediated by systemic inflammation, increased iNOS activity, and ROS production in the arterial wall. ROS scavenger (NAC) supplementation or MPO inhibition are potential therapeutic options to reverse the devastating endothelial dysfunction in chronic anemia.

Serum Amyloid A Levels and Severity of COVID-19 in Children.

OBJECTIVE: The aim of this study was to determine the availability of serum amyloid A (SAA) in the diagnosis of coronavirus disease 2019 (COVID-19), to asses disease severity and to predict hospitalization status. METHODS: Between March, 2020 and March, 2021, a total of 80 children (40 cases with COVID-19 and 40 cases in healthy group) were included in this study. Patients were divided into two groups (mild and moderate/severe) to evaluate SAA levels in terms of clinical severity and also hospitalization status. RESULTS: Comparisons between the two groups revealed that median SAA values were significantly higher in children with COVID-19 than in their healthy peers (21.45vs3.05 mg/L, P=0.002). There was no significant difference in the median serum SAA levels between mild and moderate/severe clinical disease (P=0.837). The SAA difference between the two groups with regards to hospitalization was not statistically significant (P=0.098). CONCLUSIONS: Although SAA level was found to be higher in children with COVID 19 compared to healthy controls, the sensitivity of SAA for the disease was found to be low. In addition, there was no difference between the groups in terms of clinical severity.