Vitamin D receptor (VDR), influenced by gene polymorphisms like FokI, may affect susceptibility to infections, including coronavirus disease 2019 (COVID-19). Since studies in children are limited, we aimed to analyze the correlation between the VDR FokI variant and both the incidence and severity of COVID-19 in Egyptian children.

Seventy-seven COVID-19-positive and 107 COVID-19-negative pediatric patients were included. Participants' serum 25(OH)D levels, inflammatory biomarkers, and demographics were evaluated. Real-time polymerase chain reaction (PCR) was used for genotyping the VDR FokI (rs2228570) polymorphism.

Absolute lymphocyte count (ALC) was significantly lower in COVID-19 patients than in controls, while interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and D-dimer were significantly higher (all p < 0.001). Vitamin D insufficiency was significantly more common in COVID-19 cases (18.2 % versus 3.7 %, p = 0.002). Male sex, increased tumor necrosis factor-alpha (TNF-α), and CRP were significantly associated with severe COVID-19 (p = 0.032, 0.029, < 0.001, respectively). The FokI TT genotype in codominant and recessive models and the T allele in the multiplicative model were significantly correlated with 2.4, 3.0, and 1.8 folds increased COVID-19 risk (p = 0.043, < 0.001, and 0.004, respectively). However, VDR FokI variants did not significantly associate with severe COVID-19.

The T allele and TT genotype of the FokI variant in the VDR gene increase susceptibility to COVID-19 but not its severity in Egyptian children. Additional research is required to validate the potential role of vitamin D and its receptor polymorphism in COVID-19.

Knowledge of the effect of SARS-CoV-2 on the innate and adaptive immune responses of children is currently lacking. We investigated the immune profile of recovered pediatric patients 3 to 11 weeks after acute COVID-19.

Children who were previously healthy or had a preexisting chronic disease and had a positive reverse transcription polymerase chain reaction/serology were enrolled (n=23). The control group was composed of 25 patients without COVID-19 paired by age, sex and baseline chronic conditions. We performed immunophenotyping, hematologic and inflammatory markers analysis, cytokines and T-cell receptor excision circle (TREC) quantifications.

Most COVID-19 convalescent pediatric patients (COVID-19 CPP) had chronic conditions (73.9%), as well as 80% of the controls. Five children developed multisystem inflammatory syndrome in children. COVID-19 CPP had higher lymphocyte numbers than controls due to an increase in CD4+ T cells. Naive, effector memory (EM) reexpressing CD45RA T cells and follicular CD4+ T cells, as well as TRECs and HLA-DR+ and CD38+CD4+ activated T lymphocytes, were increased in those patients. EM2 and EM3 CD4+ T cells, EM2 CD8+ T cells and memory B cells were elevated in the COVID-19 CPP group. Numbers of neutrophils, monocytes and natural killer cells were equivalent but with increased activation in the recovered patients.

In the short-term following infection, COVID-19-recovered patients show persistent activation profiles in phagocytes, T-cell subtypes and natural killer cells. Meanwhile, increased production of lymphocytes, TRECs and naive T cells suggests immune response recovery, even in immunosuppressed patients and children with comorbidities. The clinical implications of these findings should be further studied.

Compared to adults, children are more likely to experience asymptomatic infections or mild-to-moderate symptoms of SARS-CoV-2 infection that resemble other viral infections. However, a substantial proportion of children experience severe disease; more than 2000 US children have died of COVID-19, significantly exceeding the death toll from influenza. Risk factors for severe disease include age less than 6 months and 12 to 17 years, as well as the presence of underlying conditions, especially 2 or more conditions. Multisystem inflammatory syndrome in children is a life-threatening post-infectious complication seen in children. Children experience post-acute sequelae of SARS-CoV-2 but at lower rates than adults.

To quantify the impact of the COVID-19 pandemic on paediatric care use compared to adult care and identify affected subdomains.

Data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) for six fiscal years (FY2016-2021) were analysed. Pre-pandemic (FY2016-FY2019) and pandemic years (FY2020, FY2021) were compared to delineate changes in medical services for paediatric and adult patients. Virtually all individuals who received medical care in Japan during this period were included.

In FY2019, healthcare utilisation by the paediatric population (under 15 years) accounted for 24% of 245 million first outpatient visits, 7% of 1.2 billion follow-up visits, and 2.6% of 297 million patient-days hospitalisations. In FY2020, outpatient visits of those aged 0-4 years decreased by 44% (first visit) and 24% (follow-up visit) compared to FY2019, and hospitalisations decreased by 47%, with the largest declines observed in community medical institutions across all age groups.

The COVID-19 pandemic led to a substantial reduction in paediatric healthcare utilisation in Japan, varying by age and type of care. These findings may inform the rational allocation of healthcare resources during public health emergencies.

Infection by the SARS-CoV-2 virus can cause coronavirus disease 2019 (COVID-19) and can also exacerbate the symptoms of Kawasaki disease (KD), an acute vasculitis that mostly affects children. This study used bioinformatics and machine learning to examine similarities in the molecular pathogenesis of COVID-19 and KD.

We first identified disease-associated modules in KD using weighted gene co-expression network analysis. Then, we determined shared differentially expressed genes (DEGs) in training datasets for KD (GSE100154) and COVID-19 (GSE225220), performed functional annotation of these shared DEGs, and used Cytoscape plug-ins (MCODE and Cytohubba) to characterize the protein-protein interaction (PPI) network and identify the hub genes. We performed Least Absolute Shrinkage and Selection Operator(LASSO) regression and receiver operating characteristic (ROC) curve analysis to identify the most robust markers, validated these results by analysis of two other datasets (GSE73461 and GSE18606), and then calculated the correlations of these key genes with immune cells.

This analysis identified 26 shared DEGs in COVID-19 and KD. The results from functional annotation showed that the shared DEGs primarily functioned in immune responses, the formation of neutrophil extracellular traps, and NOD-like receptor signaling pathways. There were three key genes (PGLYRP1, DEFA4, RETN), and they had positive correlations with monocytes, M0 macrophages, and dendritic cells, which function as immune infiltrating cells in KD.

The potential immune-associated biomarkers (PGLYRP1, DEFA4, RETN) along with their shared pathways, hold promise for advancing investigations into the underlying pathogenesis of KD and COVID-19.

BackgroundCOVID-19 disproportionately affected individuals from marginalized and underserved communities, and little research has investigated how COVID-19 might have impacted neurobehavioral symptoms in children from Latin America. What little research suggests that COVID-19 had a negative effect on neurobehavioral symptoms and that this effect was worse for individuals who were younger, had lower education, or other chronic conditions.ObjectiveThe purpose of the current study was to examine the change (before, during, and after) in neurobehavioral symptoms for a sample of Colombian children who tested positive for COVID-19 and to identify key predictors of post-COVID neurobehavioral impairments.MethodsThe Neurobehavioral Symptom Inventory was administered to caregivers (92.90% female) of 85 children (51.80% female) by researchers in Colombia. Data was collected after the child had recovered from COVID-19 with retrospective questions about the child's function before and during COVID-19, as well as at the time of data collection.ResultsAt the domain level, caregivers reported large increases in children's somatic symptoms, a medium increase in affective symptoms, and a small increase in cognitive symptoms before vs. during COVID-19. Caregivers also noted a large increase in children's somatic symptoms, a medium increase in affective symptoms, and a small increase in cognitive symptoms before vs after COVID-19. The somatic symptom domain was the only category to see an improvement following infection (during vs after). Three separate linear regressions indicated that greater COVID-19 severity during the infection significantly predicted greater current (after COVID-19) somatic symptom severity, and the presence of a pre-existing respiratory disease significantly predicted greater current cognitive and affective symptom severity.ConclusionThis study highlights the importance of evaluating and treating neurobehavioral symptoms post-COVID-19 among children in Colombia and identifies this need in an underserved and under-researched population. Future research may examine whether early intervention and rehabilitation strategies help improve post-COVID-19 neurobehavioral symptoms for this group.

Among adults who develop coronavirus disease 2019 (COVID-19), those with rheumatic diseases (RDs) have similar hospitalization rates compared with those without RDs. Similar comparisons are lacking in children, due to the overall rarity of COVID-19-related hospitalization in this population. We aimed to examine the risk factors for COVID-19-related hospitalization in paediatric patients with RDs.

We conducted a systemic literature search in MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure from 1 December 2019, through 22 January 2024. We included observational studies based on inclusion and exclusion criteria. Odds ratios (ORs) with 95% CI were calculated.

Eight cohort studies capturing 1501 paediatric RD patients with SARS-CoV-2 and 118 COVID-19-related hospitalization were included. Odds of hospitalization was increased in children with RDs compared with healthy children. While the diagnosis of juvenile idiopathic arthritis (JIA) was associated with reduced odds of hospitalization overall (OR 0.43 [95% CI: 0.27, 0.68]), systemic JIA was associated with increased odds of hospitalization (OR 2.54 [95% CI: 1.01, 6.40]). The use of glucocorticoids (OR 5.36 [95% CI: 2.21, 13.04]), rituximab (OR 4.62 [95% CI: 1.87, 11.40]), mycophenolate mofetil (OR 4.17 [95% CI: 1.08, 16.16]), hydroxychloroquine (OR 2.97 [95% CI: 1.42, 6.21]), and IL-1 inhibitors (OR 2.28 [95% CI: 1.09, 4.78]) was associated with increased odds of hospitalization, while the use of TNFα inhibitors was associated with reduced odds (OR 0.35 [95% CI: 0.20, 0.66]).

Children with RDs are at risk of severe COVID-19 outcomes, while children with JIA taking TNFα inhibitors might be at a lower risk.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected hundreds of millions of people globally, resulting in millions of deaths. During this pandemic, children have demonstrated greater resistance than adults, exhibiting lower infection rates, reduced mortality, and milder symptoms. Summarizing the differences in resistance between children and adults during COVID-19 can provide insights into protective mechanisms and potential implications for future treatments. In this review, we focused on summarizing and discussing the mechanisms for better protection of children in COVID-19. These protective mechanisms encompass several factors: the baseline expression of cell surface receptor ACE2 and hydrolase TMPRSS2, the impact of complications on COVID-19, and age-related cytokine profiles. Additionally, differences in local and systemic immune responses between children and adults also contribute significantly, particularly interferon responses, heterologous protection from non-COVID-19 vaccinations, and immune status variations influenced by micronutrient levels. The advantageous protection mechanisms of these children may provide insights into the prevention and treatment of COVID-19. Importantly, while age-related metabolic profiles and differential COVID-19 vaccine responses may contribute to protection in children, current comparative research remains limited and requires further investigation.

COVID-19 has emerged as a global pandemic affecting individuals of all ages. The disease can lead to severe complications and even death, particularly due to pulmonary involvement. Contrary to popular belief, children can also experience significant complications from COVID-19. To date, there have been limited studies focusing on pulmonary manifestations in pediatric patients with COVID-19. This study aims to investigate the imaging patterns (CT scans) in children diagnosed with COVID-19 in Iran.

This retrospective study analyzed data from hospitalized children with COVID-19 in Tehran from March 2020 to September 2020. Information collected included demographic details (sex and age), previous medical history, clinical manifestations, vital signs at admission, laboratory findings, and imaging results, including CT scan and chest x-ray.

252 patients were included, with a mean age of 71.2 ± 59.42 months; 58.3% were male. Fever was the most prevalent symptom, occurring in 67.4% of cases. The most common underlying condition was oncological disorders, present in 85% of patients. Notably, 52% required admission to the ICU, and 1.8% needed intubation. CT scans revealed that the most frequent lung involvement patterns were mixed patterns and consolidation, with bilateral involvement being the most common. The mean CT score was calculated at 3 ± 4. Abnormal CT findings were associated with a poorer prognosis, and correlations were observed between specific CT findings and clinical manifestations.

Chest CT manifestations offer valuable insights for assessing pediatric patients with COVID-19, especially in severe cases and those with pre-existing health conditions. Integrating clinical evaluations with radiological scoring systems facilitates early identification of disease severity.

Despite several publications covering patients from multiple centers, no international registry covered all patients with red blood cell diseases (RBCD) affected by COVID- 19. The ERN-EuroBloodNet's registry provided real-time registration of SARS-CoV- 2 patients with RBCD, promoting timely disease-specific knowledge sharing during the pandemic's early stages.

The study evaluated patient distribution, the infection across different RBCDs, and severity risk factors across similar healthcare systems, using data collected from the ERN-EuroBloodNet's REDCap platform.

From April 2020 to April 2023, 681 infections were recorded among 663 patients, of which 373 had transfusion-dependent thalassemia or non-transfusion-dependent thalassemia (TDT/NTDT), and 269 had sickle cell disease (SCD). SCD patients had a higher incidence of COVID- 19 than those with TDT/NTDT (10.5 vs. 4.8 COVID/100 patients). Notably, 92% of the cases were mild, with neither age nor the specific RBCD affecting severity. The number of comorbidities, notably obesity and hypertension, that patients had prior to infection was associated with more severe COVID- 19. During the infection, the presence of vaso-occlusive crises, acute chest syndrome, kidney failure, and ground-glass opacities on chest tomography scans were associated with a more severe clinical picture. The vaccination rate (32%) mirrored that of the general population and showed a protective effect against severe COVID- 19. The observed mortality rate was 0.7%, aligning with Europe's general population.

SARS-CoV- 2 infection in SCD and TDT/NTDT patients is mild and without higher mortality than the general population. The ERN-Eurobloodnet's registry collaborative structure exemplifies the power of international cooperation in tackling rare diseases, especially during health emergencies.

This observational prospective longitudinal multicenter study examines the occurrence and characteristics of long COVID (LC) in the Italian pediatric population.

Conducted across 12 Pediatric Units in Italy from January to March 2022, the study involved 1129 children diagnosed with SARS-CoV-2 infection. Data were collected via self-administered questionnaires at 1-3 months, 3-6 months, and 6-12 months post-infection, with LC defined as symptoms persisting for at least 2 months and occurring 3 months post-diagnosis.

Results revealed that 68.6% of children reported at least one post-COVID symptom, with 16.2% experiencing LC. The most frequent symptoms included respiratory issues (43.4%), neurological and cognitive dysfunction (27.7%), gastrointestinal symptoms (22.1%), fatigue (21.6%), and sleep disturbances (18.8%). Age and gender differences were significant, with older children and females more prone to cardiovascular and neurological & cognitive dysfunction.

The study highlights that LC in children presents similarly to adults, though less frequently. The occurrence of LC was lower compared to adult populations, likely due to the generally milder course of COVID-19 in children. The findings underscore the need for targeted follow-up and support for affected children, especially considering the long-term persistence of symptoms. Further research is necessary to explore the impact of COVID-19 vaccines on pediatric LC and the effects of different SARS-CoV-2 variants. These insights are crucial for developing strategies to manage and mitigate long-term impacts in children recovering from COVID-19.

Objectives: This study assessed the clinical characteristics of pediatric COVID-19 patients across different age groups during the first and second pandemic waves in Jordan. Methods: A retrospective analysis was conducted at Jordan University Hospital, involving 485 patients aged 1 month to 18 years from September 2020 to July 2021. Patients were categorized into preschool (≤5 years), school-aged (6-10 years), and teenagers (>10 years). Patients' clinical characteristics were analyzed using R (version 2.3.3). Results: The mean age for participants was 10.7 ± 5.7 years. Shortness of breath, abdominal pain, and headaches were significantly more likely among older participants (all p < 0.01). Conversely, younger patients were more likely to experience nasal congestion, decreased activity, and reduced feeding (all p < 0.05). The majority of patients had mild symptom severity. Analysis of physiologic and laboratory parameters demonstrated significant differences among age groups in terms of heart rate, respiratory rate, hemoglobin, neutrophils, lymphocytes, platelets, CRP, and creatinine (all p < 0.05). Respiratory support was mainly observed among younger patients. Antibiotics was the most commonly received medication. In terms of outcomes, two patients had complications during their stay, both of which belonged to the <5 years age group. We observed significant differences in incidence of symptoms and laboratory markers among different pediatric age groups. While younger patients experienced severe complications, their older counterparts exhibited more alarming symptoms and worse counts of immune cells. Conclusions: These findings highlight the importance of age-specific management strategies for COVID-19, emphasizing the need for tailored approaches in both treatment and prevention.

Severe lung disease such as chronic pulmonary disease (CPD), severe asthma and cystic fibrosis (CF) in children is associated with increased risk of severe COVID-19. Information regarding SARS-CoV-2 infection, disease severity and outcome of COVID-19 is limited in this pediatric population.

We captured the number of SARS-CoV-2 infected children and evaluated COVID-19 disease severity in non-immunized children with CPD, asthma, and CF in a cohort at a Danish tertiary center.

The number of children with PCR-verified SARS-CoV-2 infection in the cohort and in the age-related background population was identified through the Danish Microbiology Database. Clinical data were retrieved from the electronic medical health records and from the Danish Health Authority.

In a cohort of 664 children with severe lung disease 594 were either PCR-tested or had an antibody test for SARS-CoV-2 infection due to symptoms or exposure and 18 (3%) had verified SARS-CoV-2 infection. The total number of verified SARS-CoV-2 infection was at that time 34.575(4.342%) thus, not significantly different from the reference population (p = 0.152). The symptoms ranged from asymptomatic to mild symptoms, and none of the children with severe lung disease required hospitalization due to COVID-19. None of the children were treated with antiviral treatment during the acute infection.

Of the 664 children in the Danish cohort with severe lung disease, none were hospitalized with COVID-19. Our findings imply that this particular group of patients do not experience increased risk of severe COVID-19.

Numerous inflammatory complications related to COVID are described, including the Multisystem inflammatory Syndrome in Children (MIS-C) and Hyperinflammation. There is a scarcity of studies comparing these two groups.

Retrospective longitudinal outcome-conditioned study. Demographic, clinical, and laboratory variables are analyzed. Patients with history of COVID contact or infection with at least 24 h of fever, two or more systems involved and up to 21 years were included. Patients with no laboratory signal of inflammation or with other diagnoses for the condition were excluded. Demographic and laboratory data are presented as medians with interquartile ranges. Dichotomous variables and prevalences are reported as percentages. A ROC curve analysis was conducted to assess the discriminatory ability of these tests in relation to the MIS-C and hyperinflammation groups.

We present fifty-four patients, thirty-one with MIS-C and twenty-three with hyperinflammation. The most frequent symptom in the MIS-C group was altered mental status in 61% vs. 46% (p = 0.014) and conjunctival hyperemia in 29% vs. 4% (p = 0.032). The most frequent laboratory findings were hypoalbuminemia in 68% vs. 26% (p = 0.002), increased serum troponin in 42% vs. 26% (p = 0.034), increased d-dimers in 94% vs. 76% (p = 0.015), as well as increased BNP in 55% vs. 17% (p = 0.02). On the other hand, the hyperinflammation group more frequently presented respiratory dysfunction in 57% vs. 13% (p = < 0.001) and serum ferritin equal or greater than 500 ng/mL in 94% vs. 77% (p = 0.046).

This is an original study comparing clinical and laboratory findings between MIS-C and hyperinflammation due to COVID. Altered mental status is more frequently associated with MIS-C while respiratory symptoms are associated with hyperinflammation. In addition, regarding laboratory tests, there is hypoalbuminemia, increase in serum troponin, BNP, and D-dimers specially in the MIS-C group and hyperferritinemia in the hyperinflammation group. Further studies are needed to assess the cutoff point of biological markers such as BNP, troponin, and d-dimers for diagnosis and/or prognosis in the pediatric population with MIS-C.

Children account for a small percentage of COVID-19 cases and tend to exhibit milder symptoms compared to adults. Cardiovascular involvement has been observed in pediatric COVID-19 cases. This study aimed to determine the frequency of cardiac disorders in children hospitalized with COVID-19.

This cross-sectional study was conducted on pediatric patients admitted to Bandar Abbas Children Hospital, Iran, from March to September 2020. Patients with negative RT-PCR results for SARS-CoV-2, non-COVID-19 pulmonary involvement or pre-existing cardiovascular conditions were excluded. COVID-19 diagnostic subgroups were determined based on national guidelines. Clinical evaluations included chest CT scans to assess pulmonary involvement and cardiac assessments such as clinical symptoms, electrocardiography and echocardiography. Cardiac abnormalities were defined as clinical heart failure, dysrhythmias or abnormal echocardiography. Multivariable logistic regression was applied to analyze the associations between cardiac abnormalities, age and lung involvement, with statistical significance set at P < 0.05.

This cross-sectional study was conducted in 2020 on 475 children aged 1 month to 14 years. Among the participants, 48.4% had suspected, 30.5% had probable, and 21.1% had confirmed COVID-19. Cardiac abnormalities were identified in 35.2% of patients, including dysrhythmia (20.2%), heart failure (7.6%), and abnormal echocardiography findings (13.1%). The odds of cardiac abnormalities were 3.3 times higher in children with unilateral lung involvement and 5.9 times higher in those with bilateral lung involvement compared to those without lung involvement. Additionally, older age was associated with a 5.7% reduction in the odds of cardiac abnormalities.

Cardiac abnormalities in pediatric COVID-19 patients show a significant correlation with pulmonary involvement, highlighting their link to disease severity. Routine cardiac assessments may help identify complications and guide management, especially during sporadic cases and seasonal outbreaks.

Understanding the impact of the COVID-19 pandemic on child survival is crucial. Analysing COVID-19-related child deaths, even years after the pandemic, is critical for informing future pandemic preparedness and response efforts.

We conducted an analysis of all "SARS-CoV-2/COVID-19 positive deaths" among children and adolescents (aged < 18 years) recorded through a purposefully designed Child Death Surveillance and Response System (CDSRS) from October 2020 to September 2022. It included all deaths with a positive SARS-CoV-2. The analysis involved a thorough review of documents (bedhead tickets, field/institutional investigation and postmortem examination reports, and compiled case scenarios). Multivariable backward logistic regression was conducted to identify risk factors associated with deaths attributed to COVID-19 infection. Additionally, a comparison of socio-demographic characteristics was conducted between deaths due to all causes and those attributed to COVID-19 infection.

A total of 111 deaths with a positive SARS-CoV-2 test were analyzed. Among these, 81 deaths (73%) were categorized as directly attributed to COVID-19 infection. Fourteen children (17.2%) had Multisystem Inflammatory Syndrome. Cardiovascular disease was the most common comorbidity (28.4%). The odds of deaths attributed to COVID-19 infection were eleven times higher with chronic diseases compared to incidental SARS-CoV-2 positive test (OR:11.22, 95% CI:1.735, 72.496). Tamil ethnicity appeared to be protective when compared to the Sinhalese (OR:0.07, 95% CI: 0.008, 0.598). The model explained 44.8% of the variance. When compared to national all-cause mortality data, females (p = 0.03), post-neonatal infants (p < 0.001), and > 5-18 years (p = 0.005) were identified as being at higher risk of death due to COVID-19 infection.

The proportion of COVID-19-positive deaths during the study period was higher than that reported in high-income countries, with most deaths directly attributed to SARS-CoV-2. Higher mortality rates were observed among post-neonatal infants, children over five years, females, those with Sinhalese ethnicity, and pre-existing chronic medical conditions, particularly cardiovascular disease.

Background/Objective: Millions of children were infected with SARS-CoV-2, and a small proportion progressed to severe disease, especially those with underlying risk factors. Adult COVID-19 studies showed mortality benefits with Remdesivir. Data on Remdesivir use in pediatrics are limited. We report on the safety and tolerability of Remdesivir in pediatric patients seen at our institution. Methods: This was a retrospective cohort study of patients <19 years old with acute SARS-CoV-2 infection who received at least one dose of Remdesivir. Patients followed strict institutional guidelines for safety monitoring including standard clinical and laboratory daily observations. Demographics and underlying conditions were reported as averages; for laboratory values, linear regression was applied within a generalized linear mixed-effects model framework to evaluate the significance of changes in average levels over time. Results: We enrolled 318 patients with acute SARS-CoV2 infection from May 2020 to December 2022. In total, 53% were male, and the age range was distributed broadly. In total, 61% were school-aged children (28% 5-11 and 33% 12-18 years of age). In total, 62% of cases were Hispanic. The most common reasons for Remdesivir treatment included respiratory distress (201; 63%) and having high-risk underlying conditions (109; 34%). Therapy was completed as planned in 91% and discontinued early in 9%. Mean baseline, peak, and end of treatment values for AST were 57 (95% CI 53, 61), 79 (95% CI 73, 84) (p < 0.001), and 55 (51, 59) (p = 0.479); for ALT, they were 42 (38, 47), 59 (95% CI 52, 66) (p < 0.001), and 46 (95% CI 41, 52) (p = 0.054); and for bilirubin, they were 0.56 (95% CI 0.50, 0.62), 0.67 (95% CI 0.61, 0.74) (p < 0.001), and 0.44 (95% CI 0.40, 0.48) (p < 0.001), respectively. During Remdesivir treatment, we did not observe marrow suppression or renal toxicity. Conclusions: No clinically significant hematological or renal toxicity was noted. Mean liver enzymes increased modestly and returned to baseline without interrupting treatment. Remdesivir was well tolerated in patients <19 years old.

To investigate the prevalence and factors of COVID-19 infection in children aged 0-6 years within Hunan Province following the deregulation of epidemic control.

This is an observational study in epidemiology, using an on-site questionnaire survey to investigate the current status of COVID-19 infection and its influencing factors in children aged 0-6 years in Hunan Province from 16 February to 24 March 2023.

Multi-stage stratified sampling method was applied in this study. The regions were categorised as developed, medium and underdeveloped. One municipality was selected from each category. In each municipality, one district and one county were chosen for cluster sampling.

Children aged 0-6 years in Hunan Province.

A total of 78 115 children aged 0-6 years were enrolled in this study, of 30 659 (39.2%) had a confirmed positive SARS-CoV-2 test result or related clinical symptoms. The majority of COVID-19 infections in children were of mild type (92.0%), and very few were severe and critical (0.4% and 0.1%). The majority (74.6%-88.7%) of children had minimal lifestyle behavioural changes after infected with COVID-19. Parents of the child working as a staff member (OR=0.654, 95% CI: 0.603, 0.709) and civil servant (OR=0.865, 95% CI: 0.794, 0.941), living in a rural area (OR=0.384, 95% CI: 0.369, 0.400) and no COVID-19 exposure (OR=0.108, 95% CI: 0.104, 0.113) were protective factors for COVID-19 infection in children.

Children experienced a large number of COVID-19 infections following the deregulation, fewer severe cases and fewer changes in lifestyle. Easing epidemic control measures in the later stage of the pandemic did not aggravate the consequences of the epidemic.

This study assessed the impact of a 12-wk, home-based exercise training (HBET) program on health-related quality of life (HRQOL; primary outcome), and cardiovascular and metabolic parameters in pediatric COVID-19 patients.

This was a single-center, randomized controlled trial conducted in a tertiary hospital in Sao Paulo, from October 2020 to January 2022. Thirty-two patients (mean age, 12 ± 3.3 yr) were randomly assigned to either HBET or standard of care (CONTROL) in a 2:1 ratio 4 months (range: 0.7-6.6 months) after COVID-19 discharge ( n = 25 mild, n = 4 moderate, n = 3 severe illness). The HBET group underwent supervised and unsupervised sessions three times a week for 12 wk emphasizing aerobic and body weight exercises, while the CONTROL group received standard care, which included general advice for a healthy lifestyle with no prescribed exercise intervention. HRQOL (evaluated by the Pediatric Quality of Life Inventory), cardiopulmonary exercise test, brachial endothelial function and echocardiography assessments were conducted in both groups. Statistical analysis was performed using an intention-to-treat approach for the primary analysis and complete case (per-protocol) as sensitivity analysis.The significance was set at P ≤ 0.05 and P ≤ 0.10 was considered as trend.

There was no difference in HRQOL between groups. Intention-to-treat analysis indicated a trend toward increased oxygen uptake (V̇O 2 ) at anaerobic threshold following the intervention in the HBET group. In addition, a sensitivity analysis showed significant changes in peak heart rate and 1-min recovery, respiratory exchange ratio, and chronotropic response. A trend toward significance was observed in ventilation-to-maximum voluntary ventilation ratio and chronotropic response in the HBET group. No other between-group differences were detected for the cardiopulmonary exercise test, brachial flow-mediated dilation, and echocardiography variables (all P > 0.05).

In this randomized controlled trial, a 12-wk HBET intervention did not impact HRQOL in pediatric COVID-19 patients. However, exercise was able to improve the V̇O 2 at the ventilatory anaerobic threshold, heart rate peak and 1-min recovery, ventilation-to-maximum voluntary ventilation ratio, and chronotropic response, with no changes observed in other cardiovascular parameters. Further studies are needed to investigate the long-term effects of exercise interventions on the recovery of pediatric COVID-19 patients with and without preexisting chronic conditions.

To compare pulmonary function tests (PFTs), specifically passive respiratory system compliance (Crs), in infants of mothers positive for COVID-19 during pregnancy compared to PFTs from a historical cohort of matched, healthy reference infants.

A prospective cohort study of infants born to COVID-19 positive mothers. Crs was measured with the single breath occlusion technique. Historical cohort data was obtained from a pre-COVID-19 data repository. Respiratory questionnaires were done at 1-year postnatal age.

Twenty-four PFTs in the COVID-19 cohort were compared with PFTs from 24 reference subjects. Infants of the COVID-19 positive mothers had a Crs of 3.57 ml/cmH2O versus 3.76 mL/cmH2O in the reference group (p > 0.05). The remaining PFT outcomes were comparable between groups. The COVID-19 infants reported more allergic symptoms and conditions through 1-year.

We found no difference in Crs in infants of mothers with COVID-19 during pregnancy compared to a historical pre-COVID reference cohort.

To analyze whether there is a significant difference in the virulence, symptoms, and outcomes of different Coronavirus Disease 2019 (COVID-19) variants in children under 2-years of age. We collected data from the Sistema de Informação de Vigilância Epidemiológica da Gripe, a nationwide Brazilian database on severe acute respiratory syndrome. The patients were classified according to four variants of concern: wild-type, gamma, delta, and omicron. The wild-type variant was defined as the baseline. A total of 11,153 patients were analyzed. The risk of presenting dyspnea (adjusted Odds Ratio[Aor = 1.20], 95 % Confidence Interval [95 % CI 1.07-1.34]) was higher in patients with gamma infection. Respiratory discomfort was more likely to be present for the omicron (Aor = 1.29, 95 % CI 1.15-1.43) and gamma (aOR = 1.26, 95 % CI 1.13-1.41) infections. Desaturation was more likely to be present for the omicron (aOR = 1.67, 95 % CI 1.50-1.86), gamma (aOR = 1.16, 95 % CI 1.43-1.79), and delta (aOR 1.41, CI 95 % 1.18-1.68) infections. Infection by the omicron variant was a protective factor for intubation (aOR = 0.78, 95 % CI 0.67-0.91) and death (aOR = 0.43, 95 % CI 0.35-0.53). Additionally, delta infection was a protective factor against death (aOR = 0.60, 95 % CI 0.43-0.85). The wild-type variant was responsible for most of the cases that evolved with death. Omicron appears to be responsible for milder symptoms than delta. Children between 1 and 6 months of age account for most cases, which is a concern because there is no vaccination coverage.

Since the emergence of COVID-19 in December 2019, the novel SARS-CoV-2 virus has primarily affected adults, with children representing a smaller proportion of cases. However, the escalation of the pandemic has led to a notable increase in pediatric cases of Multisystem Inflammatory Syndrome in Children (MIS-C). The pathogenesis of MIS-C is largely attributed to immune-mediated mechanisms, such as cytokine storms and endothelial damage, following SARS-CoV-2 infection. In this review, we comprehensively describe MIS-C, including its definitions as proposed by the CDC, WHO, and RCPCH, which emphasize persistent fever, excessive inflammatory responses, and multi-organ involvement. Additionally, we summarize current treatment approaches, prioritizing immunotherapy with intravenous immunoglobulin and corticosteroids, along with anticoagulation therapy, and monoclonal antibodies in severe cases.

We analyzed 364 children symptomatic or asymptomatic for respiratory symptoms, aged 0.1 month-17 years, selected from primary healthcare units of different municipalities of Rondônia from June 2021 to September 2022. Data were collected from medical and electronic records for epidemiological characterization. The positive cohort (n = 96) was quantified using a real-time (RT) qPCR and sequenced by next-generation sequencing. Whole-genome sequences were obtained, SARS-CoV-2 strains were classified using the Pango system, and the maximum likelihood method was used for phylogenetic analyses. Among the patients, 59.34% (216/364) were male and 40.66% (148/364) were female. Children aged 10-14 years showed the highest rate of SARS-CoV-2 positivity. At the time of collection, 54.12% (197/364) of the patients were not age-eligible for immunization against COVID-19. The unvaccinated group accounted for 34.07% (124/364), with the highest proportion in the age groups of 5-9 and 10-14 years. Most patients exhibited mild symptoms. Seventy-nine high-quality genomes were obtained: Delta variant of concern (VOC) was the most prevalent (most abundant strain: AY.99.2), Omicron VOC was reported in 26 individuals (most frequent subvariant: BA.1.1), and Gamma VOC with 22 cases (12 cases of P.1 strain). The viral load showed a median of 7.26 log10 copies/mL, with a mean symptom duration of 4 days. Most of the cases were from children who were unvaccinated and age-ineligible for immunization and were associated with Delta and Omicron VOCs with an increase in subvariants during the study period.

Elucidation of immune response differences is critical for uncovering underlying mechanisms and developing potential intervention measures among adults and children with COVID-19.

In this retrospective study, we analyzed serum biochemical markers and cytokine profiles among adults and children with COVID-19 in the First People's Hospital of Chenzhou in Hunan, China from 1 December 2022 to 13 February 2023. A case-control study was conducted using propensity score matching (PSM) to mitigate possible confounding factors.

The significant differences observed included lymphocyte exhaustion, an increased neutrophil-to-lymphocyte (NEU/LYM) ratio, high levels of C-reactive protein (CRP), and a cytokine storm, characterized by high levels of Th1 proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-8, interferon type I (IFN-γ), and tumor necrosis factor (TNF-α) in the lung among severe adult COVID-19 patients. Additionally, systemic immune responses were observed in children with COVID-19.

Significant differences in immune responses between adults and children with COVID-19 highlight the different mechanisms and potential intervention measures of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children. Currently available treatment and prophylaxis strategies will be outlined, with the caveat that new therapeutics and clinical efficacy data are constantly on the horizon.

There are limited data regarding changes in glucose control in pediatric patients with type 1 diabetes (T1D) affected by coronavirus disease 2019 (COVID-19). This study aimed to evaluate changes in the metrics of a continuous glucose monitoring (CGM) system during COVID-19 infection in children and adolescents with T1D.

Eighteen patients with T1D (<18 years of age) were included in this retrospective study. The effects of COVID-19 on CGM metrics were assessed at 5 time points (2 weeks before COVID-19 [time 1], 1 week before COVID-19 [time 2], during COVID-19 [time 3], 1 week after COVID-19 [time 4], and 2 weeks after COVID-19 [time 5]).

All participants had at least 1 symptom of COVID-19 and did not need to be hospitalized. The glucose management indicator (GMI) was higher at time 3 (7.7%±1.4%) compared to time 1 (7.1%±1.1%; P=0.016) and time 5 (7.0%±1.2%; P=0.008). According to the insulin delivery method, the GMI at time 3 was significantly higher than that at time 5 in patients treated with multiple daily injections (MDI) (median and interquartile range, 8.0% [6.1%-8.5%] vs. 7.1% [5.8%-7.9%]; P=0.020) but not in those treated with continuous subcutaneous insulin infusion (CSII).

Pediatric patients with T1D and mild COVID-19 showed worsening glycemic control during COVID-19 infection, but it returned to preinfection levels within 2 weeks of infection. CSII is more effective in maintaining stable glycemic control during COVID-19 infection than is MDI therapy.

Most individuals show immunity to SARS-CoV-2 from vaccination or infection, or both. We aimed to determine the safety and immunogenicity of an omicron-containing COVID-19 vaccine (mRNA-1273.222) in vaccine-naive adolescents who were SARS-CoV-2 positive.

Part 3 of the phase 2/3 TeenCOVE trial was a phase 3, open-label, single-arm part done in the USA and the Dominican Republic that enrolled healthy, vaccine-naive adolescents (aged 12-17 years) to receive two 50 μg doses of mRNA-1273.222 (ancestral strain Wuhan-Hu-1 and omicron subvariants BA.4 and BA.5), 6 months apart. Primary reactogenicity and safety outcomes included assessment of solicited local or systemic adverse reactions 7 days after vaccination, and unsolicited and prespecified adverse events throughout study participation. Inferred effectiveness (primary immunogenicity outcome) was established by comparing neutralising antibody responses 28 days after dose 1 of mRNA-1273.222 in SARS-CoV-2-positive adolescents with responses 28 days after dose 2 of mRNA-1273 100 μg primary series in SARS-CoV-2-negative young adults (aged 18-25 years) from the COVE trial. This study is registered with ClinicalTrials.gov (NCT04649151).

Between Dec 21, 2022, and June 5, 2023, 379 adolescents (378 of whom were SARS-CoV-2 positive) received at least one mRNA-1273.222 dose and were included in the safety analysis set. The reactogenicity profile was favourable compared with the mRNA-1273 primary series, with no new safety concerns identified. Unsolicited adverse events were reported in 49 (13%) of 379 participants; no deaths or adverse events leading to study discontinuation were reported. The immunogenicity set included 245 adolescents from the per-protocol immunogenicity subset who were SARS-CoV-2 positive at baseline and 296 young adults who were SARS-CoV-2 negative. Compared with the mRNA-1273 primary series in SARS-CoV-2-negative young adults, a single dose of mRNA-1273.222 induced superior (geometric mean ratio [GMR] 95% CI lower bound >1) neutralising antibody responses against omicron BA.4 and BA.5 (GMR 48·95 [95% CI 44·21-54·21]) and non-inferior (GMR 95% CI lower bound >0·667) neutralising antibody responses against ancestral SARS-CoV-2 (GMR 4·25 [95% CI 3·69-4·88]) in SARS-CoV-2-positive adolescents.

In vaccine-naive, SARS-CoV-2-positive adolescents, single-dose mRNA-1273.222 was effective against COVID-19 based on successful immunobridging to the two-dose mRNA-1273 primary series in young adults. The findings support a simplified single-dose vaccination schedule with variant-containing mRNA vaccines, regardless of previous vaccination status.

Moderna.

To investigate the infection status and outcomes of biliary atresia (BA) patients during the coronavirus disease 2019 (COVID-19) pandemic in Chinese population.

This retrospective study involved Kasai-postoperative BA patients who had achieved jaundice-free during the SARS-CoV-2 outbreak from December 1, 2022 to February 28, 2023. Children without hepatobiliary diseases hospitalized during the same period were as control group. Data collected included nutritional status, comorbidities, epidemiologic characteristics, fever symptoms (duration, max), respiratory symptoms (cough, runny nose and shortness of breath), and gastrointestinal symptoms (diarrhea and vomiting). All cases infected with SARS-CoV-2 were followed up for 3 months.

A total of 128 BA patients were enrolled, ranged in age from 6 months to 12 years old (median age: 1.8 years). A total of 51 (39.8%) and 49 BA patients (38.3%) were classified as confirmed and suspected COVID-19 cases, respectively. Only two confirmed cases presented with moderate symptoms, while the rest developed asymptomatic or mild cases. Compared to the 115 control groups, the proportion of symptomatic cases in BA was slightly higher (78.1% vs. 67.8%) without significant difference (p = 0.07). Similarly, no differences were found in proportion of fever, respiratory tract symptoms and gastrointestinal symptoms between BA and control groups. However, it is worth noting that 7 BA patients developed symptoms of cholangitis during SARS-CoV-2 infection, who experienced pale stool and elevated bilirubin levels. After hospitalization, six patients achieved jaundice-free survival, but one child finally had to undergo liver transplantation due to hepatic failure.

The symptoms and course of COVID-19 in BA patients were similar to those in healthy population. The vast majority of BA patients made a good recovery from COVID-19.

Parental vaccine hesitancy has been a hotly debated issue long before the COVID-19 pandemic. Still, the emergence of a new vaccine during this public health crisis made even pro-vaccine individuals reconsider vaccines for their children. This scoping review was conducted to understand why parents expressed hesitancy towards the COVID-19 vaccine for children under 12 years old. The search included primary sources of evidence published in English from 2020-2022. A final 41 articles met the criteria. Overall, more vaccine-hesitant characteristics were non-white, female, lower education level, lower income, on public insurance, conservative political affiliation, younger age, and rural residence. Concerns affecting confidence in the vaccine were the risk of possible side effects and lack of trust in the development of the emergency approval of the vaccine. School nurses can acknowledge parental fears and provide parents with evidence-based information when communicating with them about vaccinations.

There is a limited understanding of the immunological differences between children and adults that protect children from developing severe coronavirus disease 2019 (COVID-19) following SARS-CoV-2 infection. Previous infection with endemic human coronaviruses (HCoVs) has been suggested as a factor. In this study, we used 100 paired residual samples collected before and during the COVID-19 pandemic from children in Bangladesh. We compared the changes in their sero-status (no COVID-19 vs. COVID-19) and quantified antibody levels to HCoVs. We found that although 45% of the children seroconverted for IgG antibodies against SARS-CoV-2, there was no correlation between evidence of previous infection with HCoVs and the magnitude of SARS-CoV-2 antibody responses post-infection. Moreover, no differences in the anti-HCoV antibody levels were found pre- and post-SARS-CoV-2 infection.

Background: The risk of neonatal SARS-CoV-2 infection from the mother's own milk (MoM) in neonates who are exposed to maternal SARS-CoV-2 during the perinatal period remains unclear. We conducted a systematic review to assess the association between MoM feeding and neonatal SARS-CoV-2 infection in neonates who were born to SARS-CoV-2-positive pregnant persons. Methods: PubMed Central and Google Scholar were searched for studies published by 14 March 2024 that reported neonatal SARS-CoV-2 infection by feeding type. This search, including Scopus, was updated on 17 December 2024. The primary outcome was neonatal SARS-CoV-2 infection. The meta-analysis was conducted using a random effects model with two planned subgroup analyses: time of maternal PCR testing (at admission vs. previous 2 weeks) and dyad handling (isolation vs. some precautions vs. variable/NA). Results: The primary outcome was available in both arms of nine studies, including 5572 neonates who received MoM and 2215 who received no MoM. The GRADE rating was low quality, because the studies were observational (cohorts). The frequency of SARS-CoV-2 infection was similar in both arms (2.7% MoM vs. 2.2% no MoM), with a common risk ratio of 0.82 (95% confidence interval 0.44, 1.53, p = 0.54). No significant differences were observed in the subgroup analyses. Limitations include observational and incomplete data, other possible infection sources, small sample sizes for subgroup analyses, and neonates with more than one feeding type. Conclusions: Feeding MoM was not associated with an increased risk of neonatal SARS-CoV-2 infection among neonates who were born to mothers with perinatal infection. These data, along with reports showing a lack of active replicating SARS-CoV-2 virus in MoM, further support women with perinatal SARS-CoV-2 infection feeding MoM. Registration: PROSPERO ID CRD42021268576.

This study aimed to evaluate pathological findings on abdominal ultrasonography upon admission of children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) that were associated with a more severe disease course and the need for intensive care unit (ICU) admission. This retrospective and observational study was conducted between March 2020 and May 2022. Abdominal ultrasonography findings were evaluated in children diagnosed with MIS-C associated with SARS-CoV-2. Ultrasound examinations were conducted within the first 24 h following hospital admission. Clinical severity was categorized as mild-moderate or severe based on the highest clinical severity score observed at any point during hospitalization, using the criteria of dehydration, oxygen or inotropic requirements, cardiac involvement, and respiratory support. The indications of ICU admission were decreased ejection fraction, pulmonary involvement, and any signs of shock. We compared the presence of any individual ultrasonography findings with clinical severity and the need for ICU admission. Multivariable logistic regression analysis was performed to identify independent sonographic predictors of clinical severity and ICU admission. A total of 70 children were included in the study, 16 of whom (23%) were categorized as having severe diseases. ICU admission was required for 14 children (20%), 13 of whom had severe disease. Notably, three children with severe clinical scores did not require ICU admission. The most common ultrasonography findings were intra-abdominal free fluid (41%), hepatomegaly (36%), splenomegaly (33%), mesenteric inflammation (21%) and mesenteric lymphadenopathy (%19). Intra-abdominal free fluid (p < 0.001; OR = 18.20; 95% CI, 3.69-89.86), mesenteric inflammation (p < 0.001; OR = 10.29; 95% CI, 2.80-37.83), mesenteric lymphadenopathy (p = 0.007; OR = 6.22; 95% CI; 1.69-22.88), and hepatosplenomegaly (p = 0.039; OR = 3.89; 95% CI, 1.15-13.17) were substantially associated with severe clinical outcomes. Intra-abdominal free fluid (p < 0.001; OR = 13.76; 95% CI, 2.77-68.29) and hepatosplenomegaly (p = 0.002; OR = 8.00; 95% CI, 2.19-29.25) were significantly more common in children who required ICU admission. Multivariable logistic regression analysis revealed that intra-abdominal free fluid was an independent predictor of severe disease (p = 0.026; OR = 7.41; 95% CI, 1.28-43.00) and ICU admission (p = 0.007; OR = 9.80; 95% CI, 1.88-51.04).

Abdominal ultrasonography findings may indicate clinical severity in children with MIS-C. Intra-abdominal free fluid strongly correlates with severe clinical outcomes and the need for intensive care.

• Abdominal ultrasonography findings in children with MIS-C are non-specific and include intra-abdominal free fluid, mesenteric lymphadenopathy, and hepatosplenomegaly. • MIS-C is associated with significant systemic inflammation and can present with a variety of extracardiac symptoms, often overlapping with acute abdominal conditions.

• Intra-abdominal free fluid on ultrasonography is strongly associated with severe clinical outcomes and the need for ICU admission in MIS-C patients • This study identifies intra-abdominal free fluid as an independent sonographic predictor of disease severity and intensive care needs, emphasizing the importance of early abdominal ultrasonography in MIS-C management.

Children have been largely spared from serious disease through the COVID-19 pandemic despite a high exposure to SARS-CoV-2. Antibody responses to exposure and their role in protecting children from subsequent variant infection remain poorly understood.

This is a prospective cohort study of children in a South African community through ancestral/Beta/Delta/Omicron BA.1/BA.2 and BA.4/BA.5 SARS-CoV-2 waves (March 2020-October 2022). Health seeking behavior/illness was recorded and postwave serum samples measured for immunoglobulin (Ig) G to spike (S) (CoV2-S-IgG) by electrochemiluminescent immunosorbent assay. To estimate the protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter.

Despite little disease, 125 per 366 (34.2%) children (median age 6.7 years [interquartile range 5.99-7.4 years]) were seropositive after wave I, rising to 53.6%, 76.0%, and 96.2% and 99.2% after waves II (Beta), III (Delta), and IV and V (Omicron variants), respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection, with the greatest protection for Beta and least for Omicron. The levels of IgG specific for ancestral S antigen that provided a 50% protective threshold for the subsequent wave were lowest for the Beta and highest for the Omicron BA.1/BA.2 wave. In the multivariate analysis, maternal seropositivity (adjusted odds ratio = 2.57 [95% confidence interval: 1.72-3.82]) was strongly associated with child seropositivity.

Children responded robustly to successive waves of SARS-CoV-2, mounting IgG responses to S antigen that were protective against subsequent waves. In the absence of vaccination, almost all children were seropositive after wave V but none were hospitalized, suggesting that natural immunity alone may be sufficient to protect children in a pandemic setting.

Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance.