Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Multisystem Inflammatory Syndrome in Neonates Associated with COVID-19 in Neonatal ICU of a Tertiary Care Hospital.

OBJECTIVE: Neonatal multisystem inflammatory syndrome (MIS-N) is a unique disease of neonates described in several case reports from all over the world with a myriad of presentations and the emergence of new cases. STUDY DESIGN: Retrospective case series. Place and Duration of the Study: Department of Paediatrics, Fazaia Medical College, Pakistan Air Force Hospital, Islamabad, Pakistan, from December 2021 to November 2022. METHODOLOGY: The study was conducted on neonates who were managed as MIS-N in the neonatal ICU. Data were collected and analysed on SPSS version 24. RESULTS: Patients in this study ranged from newborns to 13 days of age with a mean age of 3.27 ± 4.29 days and average gestational age of 35.18 ± 3.67 weeks. Among these neonates, 7 (63.6%) had bleeding diathesis, 11 (100%) had seizures, 8 (72.2%) presented with haemodynamic instability and shock, and 7 (63.3%) had signs of heart failure. All neonates (100%) had markedly raised SARS-CoV2 IgG antibodies, CRP, ferritin, D-dimers, interleukin 6, procalcitonin, 10 (90.9%) had hypoalbuminemia, and 7 (63.3%) had deranged coagulation profile. Cardiac involvement was seen in all neonates (100%) with raised proBNP and myocardial dysfunction on echocardiography. Pulmonary hypertension was present in 6 (54.4%) neonates. High mortality was observed at 6 (54.5%) among which 4 (66.6%) were premature neonates. CONCLUSION: MIS-N is a new disease entity which is still under research. There is a high propensity for cardiovascular system involvement and higher mortality among preterm neonates. KEY WORDS: Neonatal multisystem inflammatory syndrome (MIS-N), Multisystem inflammatory syndrome in children (MIS-C), SARS-CoV2 infection, SARS-CoV2 spike protein, SARS-CoV2 IgG antibodies.

Correlation of risk factors with systemic inflammatory response syndrome in burn patients at the Burn Center of Dr Soetomo General Hospital, Surabaya, Indonesia.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is the main cause of death in burns and is associated with high burn mortality rates. SIRS occurs when burns are in the subacute phase and is affected by several factors, such as host, trauma and management. The research was conducted at the Burn Center of Dr Soetomo General Hospital, Surabaya, Indonesia, using retrospective observational analytic research design. The aim of the study was to assess the correlation of risk factors which include age, extent of burns, cause of burns, inhalation trauma, history of hyperglycaemia, anaemia, hypoalbuminemia and ESBL infection with the incidence of SIRS. MATERIALS AND METHODS: The study is observational analytic research using a retrospective design and secondary data of all burn patients treated at the Burn Center of Dr Soetomo General Hospital, Surabaya, Indonesia from January 2018 to December 2019. RESULTS: A total of 163 burn patients were included. Among comorbidities found were inhalation trauma (39.3%), diabetes mellitus (2.5%), anaemia (14.7%), hypoalbuminemia (40.5%) and ESBL infection (1.2%). A total of 11 patients (6.7%) suffered from SIRS. The statistical analysis showed that anaemia (p=0.012), hypoalbuminemia (p=0.030) and the percentage of burns (p=0.001) were significantly correlated to the incidence of SIRS while age, sex, cause of burn injury, inhalation trauma, diabetes mellitus and ESBL infection have no significant correlation with SIRS. CONCLUSION: Burn surface area is the most influencing factor of SIRS incident. It is important to meticulously monitor patients with extensive burn areas for indications of SIRS. However, the sample size of this study was relatively small, and it used a retrospective approach, so a larger sample size and a prospective or cohort design method were recommended for further study.

Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients.

OBJECTIVES: This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. METHODS: Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. RESULTS: The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 2 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 3 BMD (ß = -1.35, 95% CI: -0.23, -0.02), lumbar 4 BMD (ß = -0.11, 95% CI: -0.30, -0.10), femur neck BMD (ß = -0.11, 95% CI: -0.18, -0.05) and Ward's triangle BMD (ß = -0.12, 95% CI: -0.20, -0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (ß = 0.33) and hip fractures (ß = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. CONCLUSIONS: Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

Sepsis death risk factor score based on systemic inflammatory response syndrome, quick sequential organ failure assessment, and comorbidities.

OBJECTIVE: In this study, we aimed to evaluate the death risk factors of patients included in the sepsis protocol bundle, using clinical data from qSOFA, SIRS, and comorbidities, as well as development of a mortality risk score. DESIGN: This retrospective cohort study was conducted between 2016 and 2021. SETTING: Two university hospitals in Brazil. PARTICIPANTS: Patients with sepsis. INTERVENTIONS: Several clinical and laboratory data were collected focused on SIRS, qSOFA, and comorbidities. MAIN VARIABLE OF INTEREST: In-hospital mortality was the primary outcome variable. A mortality risk score was developed after logistic regression analysis. RESULTS: A total of 1,808 patients were included with a death rate of 36%. Ten variables remained independent factors related to death in multivariate analysis: temperature ≥38 °C (odds ratio [OR] = 0.65), previous sepsis (OR = 1.42), qSOFA ≥ 2 (OR = 1.43), leukocytes >12,000 or <4,000 cells/mm3 (OR = 1.61), encephalic vascular accident (OR = 1.88), age >60 years (OR = 1.93), cancer (OR = 2.2), length of hospital stay before sepsis >7 days (OR = 2.22,), dialysis (OR = 2.51), and cirrhosis (OR = 3.97). Considering the equation of the binary regression logistic analysis, the score presented an area under curve of 0.668, is not a potential model for death prediction. CONCLUSIONS: Several risk factors are independently associated with mortality, allowing the development of a prediction score based on qSOFA, SIRS, and comorbidities data, however, the performance of this score is low.

COVID-19 admissions: Trying to define the real impact of infection in hospitalized patients.

INTRODUCTION AND OBJECTIVE: Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. METHODS: Retrospective cohort study including patients aged 0-18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021. RESULTS: 228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization). In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. CONCLUSIONS: In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Convergence and divergence in Kawasaki disease and multisystem inflammatory syndrome in children: results from the COVASAKI survey.

OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.

Clinical and Laboratory Biomarkers as Predictors of Severity in Pediatric Inflammatory Multisystem Syndrome-temporally Associated With SARS-CoV-2: Data From a Prospective Nationwide Surveillance Study in Switzerland.

BACKGROUND: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. OBJECTIVE: To identify factors associated with increased PIMS-TS severity in children. METHODS: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. RESULTS: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. CONCLUSION: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.

Risk of Systemic Inflammatory Response Syndrome Following Preoperative Glucocorticoids Administration in Patients After Percutaneous Nephrolithotomy: A Retrospective Cohort Study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. METHODS: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). CONCLUSION: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.

Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients.

Current state of COVID-19 in children: 4 years on.

Children have been disproportionately affected by the COVID-19 pandemic. Despite evidence of a very low risk of severe disease, children were subjected to extensive lockdown, restriction and mitigation measures, including school closures, to control the rapid spread of SARS-CoV-2 in most parts of the world. In this review we summarise the UK experience of COVID-19 in children four years into the largest and longest pandemic of this century. We address the risks of SARS-CoV-2 infection, immunity, transmission, severity and outcomes in children. We also assess the implementation, uptake, effectiveness and impact of COVID-19 vaccination, as well as the emergence, evolution and near disappearance of PIMS-TS (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) and current understanding of long COVID in children. This review consolidates current knowledge on childhood COVID-19 and emphasises the importance of continued research and the need for research-driven public health actions and policy decisions, especially in the context of new variants and future vaccines.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

PURPOSE: In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. METHODS: We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. RESULTS: There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. CONCLUSION: However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

Should we be afraid of long-term cardiac consequences in children with multisystem inflammatory syndrome? Experience from subsequent waves of COVID-19.

The purpose of the study was to assess and compare short- and long-term cardiac complications of the multisystem inflammatory syndrome in children (MIS-C) by predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants throughout the pandemic. The analysis of prospectively collected data comparing cardiac complications of MIS-C during and after hospitalization across the original/alpha, delta, and omicron waves. Cardiac complications were defined as cardiac failure with systolic function impairment or hypotension or abnormalities in echocardiographic findings (decrease in LVEF, FS, valvular insufficiency, pericardial effusion, or coronary artery abnormalities). A total of 120 patients with MIS-C admitted to the Children's Hospital of Krakow between November 1, 2020, and May 5, 2023, were included in the study (74 during original/alpha dominance, 31 delta, and 15 omicron). Patients in the omicron group were found to be younger than those in the alpha and delta groups (37 vs. 75 vs. 80 months, p = 0.03). The frequency of cardiac failure with systolic function impairment or hypotension was diagnosed more frequently in the original/alpha and delta groups than in the omicron group (44.59% vs. 41.94% vs. 13.33%, p = 0.08) also echocardiographic abnormalities changed, with rates of 60.8%, 35.5%, and 13.3% (p < 0.001) accordingly. The multivariable regression revealed an older age (OR = 1.19, 95% CI = 1.07-1.33, p = 0.002) as the only independent factors of cardiac failure with systolic function impairment or hypotension. In all patients, signs of cardiac failure resolved during the hospitalization. Moreover, in 98.3% of patients, all echocardiagraphic abnormalities resolved completely during the observation period.    Conclusion: The cardiac complications of MIS-C appeared to advance less severely in younger children during the Omicron outbreak. In long-term observation, symptoms of cardiac failure resolve completely. Similarly, also echocardiographic abnormalities normalize in the vast majority of patients. What is Known: • Knowledge about the long-term cardiac complications of MIS-C is still evolving and uncertain. • The greatest concern of MIS-C is cardiac complications, including cardiac failure and coronary artery dilatation. What is New: • Long-term observations revealed complete resolution of cardiac complications in the vast majority of patients with MIS-C, irrespective of the dominant variant. • Cardiac complications of MIS-C were less common in younger children during subsequent pandemic waves in our patient population.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

Risk of COVID-19 in pediatric population and the effects of COVID-19 vaccination: A retrospective cohort study.

OBJECTIVE: Prior studies have demonstrated the adverse effects of upper respiratory infections on the pediatric population, such as increased risk for acute otitis media (AOM). Other studies have noted decreased otitis media complaints during the COVID-19 pandemic. This project aims to identify whether individuals who tested positive for COVID-19 at the Emergency Department (ED) visit had an increased risk of developing severe complications. Additionally, we will study whether vaccination helped decrease following COVID-19 complications. METHODS: Utilizing the TriNetX database, we obtained de-identified electronic medical records for children under five and 6-10 years old from 2020-2023 in the United States. The study population was propensity-matched for gender, index age, and comorbidities. Complications within eight weeks of the ED visit were compared between COVID-19 vaccinated and unvaccinated children. Risk ratio was used to measure associations between our groups. A p-value less than or equal to 0.05 was considered significant. RESULTS: After propensity matching, a total of 211,138 children were identified. Within eight weeks after the ED visit, unvaccinated children <5 years old who tested negative for COVID-19 had a 30 % relative risk reduction for AOM, 52 % for sinusitis, 76 % for multisystem inflammatory system (MIS), 17 % for acute respiratory failure, and 37 % for septic shock when compared to those with a positive COVID-19 result (p ≤ 0.05). Unvaccinated 6-10 years old children who tested negative for COVID-19 had an 18 % risk reduction for AOM, 44 % reduction for sinusitis, 63 % reduction for MIS, and 42 % for acute respiratory failure (p ≤ 0.05) compared to those that tested positive for COVID-19. Vaccinated children with positive COVID-19 results have no significant risk of AOM or acute respiratory failure. Additionally, children 6-10 years old with positive COVID-19 results did not have a substantial risk of sinusitis. CONCLUSION: COVID-19's effects require continued investigation in children. This study showed that there are some increased risks of severe complications following this viral infection.

Assessing pattern of the Pediatric Multisystem Inflammatory Syndrome (PMIS) in children during the COVID-19 pandemic: experience from the emergency department of tertiary care center of a low-middle-income country.

BACKGROUND: Pediatric Multisystem Inflammatory Syndrome (PMIS) is a hyperinflammatory condition affecting multiple organs in children, often resembling incomplete Kawasaki Disease during later phases of COVID-19 infection. Data on PMIS in low-middle-income countries, particularly in emergency department settings, is limited. OBJECTIVES: This prospective observational study at Aga Khan University Hospital, Karachi, aimed to determine the frequency, clinical presentation patterns, and laboratory parameters of children with PMIS visiting the emergency department during the COVID-19 pandemic. Secondary objectives included assessing factors associated with in-hospital mortality. METHODS: From March 2020 to September 2021, patients meeting World Health Organization PMIS criteria were enrolled. COVID-19 testing included PCR and antibody testing. Data was collected through a questionnaire and analyzed statistically. RESULTS: Among 56 PMIS patients (85.7% male, mean age 7.67 ± 4.8 years), respiratory symptoms (70%), neurological symptoms (57%), and gastrointestinal symptoms (54%) were common presentations. Signs included delayed capillary refill time (93%), low-volume pulses (89%), and hypotension (68%). COVID-19 antibodies were positive in the majority (78.6%) while PCR was positive in 18%. Risk factors for mortality included prolonged emergency department stay, and high Ferritin and Lactate Dehydrogenase levels. CONCLUSION: PMIS affects children of all ages. Respiratory and gastrointestinal symptoms are the most frequent presentations. Elevated inflammatory markers, including LDH, Ferritin, D-dimer, and Pro-BNP, correlate with higher mortality risk.

Capillary leak syndrome was associated with more severe multisystem inflammatory syndrome in children during the COVID-19 pandemic.

AIM: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. METHODS: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. RESULTS: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. CONCLUSION: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.

Prolonged Systemic Inflammatory Response Syndrome After Cardiac Surgery.

OBJECTIVES: Cardiac surgery induces systemic inflammatory response syndrome (SIRS), leading to higher morbidity and mortality. There are no individualized predictors for worse outcomes or biomarkers for the multifactorial, excessive inflammatory response. The interest of this study was to evaluate whether a systematic use of the SIRS criteria could be used to predict postoperative outcomes beyond infection and sepsis, and if the development of an exaggerated inflammation response could be observed preoperatively. DESIGN: The study was observational, with prospectively enrolled patients. SETTING: This was a single institution study in a hospital setting combined with laboratory findings. PARTICIPANTS: The study included a cohort of 261 volunteer patients. INTERVENTIONS: Patients underwent cardiac surgery with cardiopulmonary bypass, and were followed up to 90 days. Biomarker profiling was run preoperatively. MEASUREMENTS AND MAIN RESULTS: Altogether, 17 of 261 (6.4%) patients had prolonged SIRS, defined as fulfilling at least 2 criteria on 4 consecutive postoperative days. During hospitalization, postoperative atrial fibrillation (POAF) was found in 42.2% of patients, and stroke and transient ischemic attack in 3.8% of patients. Prolonged SIRS was a significant predictor of POAF (odds ratio [OR] 4.5, 95% CI 1.2-17.3), 90-day stroke (OR 4.5, 95% CI 1.1-18.0), and mortality (OR 10.7, 95% CI 1.7-68.8). Biomarker assays showed that preoperative nerve growth factor and interleukin 5 levels were associated with prolonged SIRS (OR 5.6, 95%, CI 1.4-23.2 and OR 0.7, 95%, CI 0.4-1.0, respectively). CONCLUSIONS: Nerve growth factor and interleukin 5 can be used to predict prolonged systemic inflammatory response, which is associated with POAF, stroke, and mortality.

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.