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.

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.

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.

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.

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.

Can Serum 25-Hydroxy Vitamin D Levels Predict the Severity of Multisystem Inflammatory Syndrome in Children and COVID-19?

Objective: To determine the clinical significance of serum 25-hydroxy (OH) vitamin D levels in pediatric patients with multisystem inflammatory syndrome in children (MIS-C) and compare the vitamin D levels of these patients with those patients with Coronavirus disease-2019 (COVID-19) and healthy controls. Methods: This study was designed for pediatric patients aged 1 month to 18 years and conducted between July 14 and December 25, 2021. Fifty-one patients with MIS-C, 57 who were hospitalized with COVID-19, and 60 controls were enrolled in the study. Vitamin D insufficiency was defined as a serum 25 (OH) vitamin D level of less than 20 ng/mL. Severe MIS-C was classified as necessitating intensive care due to cardiovascular instability, the necessity for non-invasive or invasive mechanical ventilation, and/or a diminishing Glasgow coma scale. World Health Organization definition criteria were used to describe the clinical stages of COVID-19 in children and patients were divided into four groups according to the clinical severity of COVID-19: asymptomatic, mild, moderate, and severe/critical. Results: The median serum 25 (OH) vitamin D was 14.6 ng/mL in patients with MIS-C, 16 ng/mL in patients with COVID-19, and 21.1 ng/mL in the control group (p<0.001). Vitamin D insufficiency was present in 74.5% (n=38) of patients with MIS-C, 66.7% (n=38) of patients with COVID-19, and 41.7% (n=25) of the controls (p=0.001). The percentage of four or more affected organ systems was 39.2% in patients with MIS-C. The correlation between the number of affected organ systems and serum 25 (OH) vitamin D levels was evaluated in patients with MIS-C and there was a moderate negative correlation (r=-0.310; p=0.027). A weak negative correlation was found between the severity of COVID-19 and serum 25 (OH) vitamin D (r=-0.320, p=0.015). Conclusion: Vitamin D levels were insufficient in both the MIS-C and COVID groups. Furthermore, vitamin D levels correlated with the number of affected organ systems in MIS-C and the severity of COVID-19.

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.

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.

Seasonal coronaviruses infections in children: do they always cause mild illness?

BACKGROUND: Human coronaviruses (HCoVs) cause a comprehensive clinic ranging from asymptomatic course to pneumonia. We aimed to describe the HCoV infections in children to determine the clinical status and coinfection effects in a five-year retrospective surveillance study. The primary outcome was admission to the intensive care unit (ICU) and the secondary outcome was the need of high oxygen support. METHODS: Between September 2015 and November 2020, all patients whose reverse transcription polymerase chain reaction (RT-PCR) tests were positive were determined and patients with HCoVs were included in the study. Demographical characteristics, underlying chronic diseases, clinical diagnosis, laboratory data, subtypes of HCoVs, radiological findings, treatments, hospitalization, and ICU admission were analyzed. RESULTS: Of the 2606 children, the overall respiratory tract virus detection rate was 82.4%. Among these, 98 cases were HCoVs positive and of these 80 (81.6%) were under five years of age and most of the patients were admitted to the hospital in spring and 70% were a mixed infection with other respiratory viruses. Since lower respiratory tract infections are more common in HCoV coinfections, a significant difference was found in clinical diagnosis (p < 0.001). The presence of hypoxia (p=0.003) and underlying disease (p=0.004) were found to be significantly more common in patients admitted to the ICU. The presence of hypoxia, infiltration on chest X-ray, and elevated C-reactive protein levels were more frequently determined in patients who received high oxygen support (p=0.001, p=0.036, p=0.004, respectively). CONCLUSIONS: Clinical findings may be more severe if HCoVs, which generally cause mild respiratory disease, are coinfected with another viral agent.

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.

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.

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.

The Effect of Measles, Rubella, Mumps, Hepatitis A and Hepatitis B IgG Seropositivity on The Clinical Course of COVID-19 Disease in Children: Journal of Pediatric Infection

According to the preliminary report by the Chinese Disease Control and Prevention Center, most of the patients affected were aged between 30-79, and there were few patients aged under 19 (2). Since most of the studies are centered around adult patients, the reason why children have a mild course of the disease is still vague. Immunity differences, level of inflammatory response, T-lymphocyte profile, the expression level of angiotensin converting enzyme 2 (ACE 2), the level of melatonin secretion, less exposure to environmental pollutants, less presence of chronic diseases, and cross immunity developed to other viruses have been indicated among the possible reasons debated on the subject in relevant articles (6-8). [...]it has been argued that non-specific effect of attenuated live vaccines such as Bacillus-Calmette-Guerin (BCG) and Measles, Mumps, Rubella (MMR) might have a mitigating effect on COVID-19 clini-cal findings (9). Materials and Methods The study included cases whose reverse transcrip-tase-polymerase chain reaction (RT-PCR) detected positive for SARS-CoV-2 virus with the Bio-speedy SARS CoV-2 double gene RT-qPCR kit (Bioeksen-Turkey) on combined oropharyn-geal-nasopharyngeal swab sample in our hospital between March 2020 and June 2020.