Multisystem Inflammatory Syndrome In Children Research Articles

Severity predictors for multisystemic inflammatory syndrome in children after SARS-CoV-2 infection in Vietnam

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children’s Hospital from January 2022 to June 2023. The median age was 85 (range: 2–188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2–7) days. We observed independent factors related to PICU admission, including CRP ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge $$\\end{document} 50 (mg/L) (OR 2.52, 95% CI 1.39–4.56, p = 0.002), albumin ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 30 (g/L) (OR 3.18, 95% CI 1.63–6.02, p = 0.001), absolute lymphocyte count ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 2 (× 109/L) (OR 2.18, 95% CI 1.29–3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38–4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28–4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 2 (× 109/L) (OR 2.48, 95% CI 1.10–5.61, p = 0.029), albumin ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 30 (g/L) (OR 2.53, 95% CI 1.22–5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12–4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study

Background As a post-COVID complication in children, multisystem inflammatory syndrome in children (MIS-C) is important because of its varied and life-threatening manifestations. With this background, this study attempts to focus on MIS-C cases in an underprivileged rural setting in north-eastern India, with most patients being treated with methylprednisolone rather than intravenous immunoglobulin due to financial constraints. Methods In this prospective longitudinal cohort study at MGM Medical College, 27 MIS-C cases diagnosed following WHO criteria were included. Laboratory and radiological investigations, including echocardiography, were performed as required for diagnosis and to assess prognosis. Most patients were treated with methylprednisolone. A follow-up assessment was done six weeks after discharge for any residual impairment. Results The most frequently affected age group was 5–10 years (59.28%), while respiratory (48.14%) and cardiac (40.74%) were the most commonly involved systems. Logistic regression studies established a significant association between serum ferritin level and prolonged hospital stay (coefficient 0.0674, p=0.0041), possibly due to greater complications in cases with high ferritin levels. Organ impairment was found to increase the need for inotrope use (coefficient 3.8797, p=0.00584). Most cases were treated with methylprednisolone alone (85.18%) with a favourable response and no death occurred. Conclusion The favourable response in cases treated with methylprednisolone only affirms the effectiveness of the drug as a cheaper alternative in a resource-poor setting. The study highlights that higher ferritin levels in complicated cases leads to prolonged hospitalisation and the increased need for inotropes in cases with organ impairment.

Multi-System Inflammatory Syndrome in Children: Varied Presentations and Implications in the Context of COVID-19

Multi-System Inflammatory Syndrome in Children: Varied Presentations and Implications in the Context of COVID-19

Cardiac Follow up of Pediatric Patients Presented with Covid-19 Cardiovascular Affection

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 carditis, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. Aim of the Work To Follow up of Pediatric Patients Presented with Covid-19 Cardiovascular Affection. Patients and Methods This was an analytical Prospective Cohort study conducted on 33 patients with post COVID-19 infection. all patients were subjected to the following:(demographic data, clinical signs &amp; symptoms, laboratory investigations and Echocardiogrsphy at presentation, 1,6 weeks and 3months follow up from January 2021 to August 2021 to evaluate the short and mid- term effect of COVID-19 infection on cardiac function, and outcomes for pediatric multisystem inflammatory syndrome related to covid-19. Results In our study all patients fulfilled criteria of MIS-C presented with Kawasaki disease(KD)- like symptoms and gastrointestinal symptoms in addition to fever with shock or cardiac dysfunction. Our patients were presented with the following vital data: tacycardia with mean of 132.82 (18.74) beat/minute, hypotension with mean of 88.03 (14.06) (mmhg) for systolic blood pressure &amp; mean of 49.39 (14.78) mmhg for diastolic blood pressure, spo2 mean 96.27 (2) %, high grade fever of mean 38.36(0.79). KD-like features were seen in many patients (skin rash in 66.7%, conjunctivitis in 75.8% and Cardiovascular abnormalities were seen in 100% e.g. (myocardial dysfunction, valvular regurgitation, pericardial effusion and shock. Our MIS-C patients had signs and symptoms of an inflammatory state e.g.(fever, rash, conjunctivitis and diarrhea(gastroenteritis). Conclusion MIS-C is a hyper-infammatory syndrome affecting multiple organs especially the heart and is triggered by SARS-CoV-2 infection. It is usually seen 2–4 weeks following infection. In our study,IVIG and steroids might have a beneficial role in MIS-C management.

Follow Up of Cardiovascular Affection in Covid-19 Pediatrics Survivors

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare complication of (SARS-CoV-2) infection. Presenting (4–6) weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation which is mostly due to post infection immune reaction. Aim of the Work to evaluate cardiac outcomes 6 months after initial presentation with MIS-C associated with cardiac affection. Patients and Methods This was a retrospective cohort study on 28 patients (19 boys &amp; 9 girls) who were diagnosed as multi system inflammatory syndrome in children (MIS-C) related to COVID19 six months ago at children`s hospital, Ain shams university from January 2021 to October 2021. All patients were subjected to the following: (demographic data, clinical signs and symptoms, laboratory investigations) in the acute phase (obtained from patient’s medical records) and at follow up after 6- months. Results in our study all patients fulfilled criteria of MIS-C presented with fever, shock or cardiac dysfunction and gastrointestinal symptoms in addition to conjunctivitis and skin rash. Our patients were presented with hypotension with mean systolic blood pressure (87) mmHg &amp; mean diastolic blood pressure (48) mmHg. Regarding symptoms: vomiting was seen in (60.7%), diarrhea in (32.1%), conjunctivitis in (82.1%) and cardiovascular abnormalities were seen in (100%) in the form of (myocardial dysfunction in (50%), coronary dilatation in (28.8%), valvular regurgitation in (100%) and pericardial effusion in (7.2%)). After 6 months there was significant improvement regarding vital signs. Regarding laboratory findings: at time of presentation most of the patients had high CRP, high troponin, and high CK-MB. On follow up after 6 months, all patients had normal values. Conclusion Our follow up study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children.

COVID-19 Related Multi-System Inflammatory Syndrome in Children (MIS-C): A Systematic Review

Context: Multisystem inflammatory syndrome in children (MIS-C) is a severe condition associated with SARS-CoV-2. The underlying reasons why some children develop MIS-C remain unclear. Objectives: To review and summarize the existing evidence about the epidemiological and clinical characteristics, laboratory findings, therapeutic management, and outcomes of patients with COVID-19-related MIS-C. Methods: This systematic review followed PRISMA guidelines. We searched PubMed and Google Scholar for studies on COVID-19 and MIS-C. Out of the 2026 research articles generated from our initial search on PubMed and Google Scholar on 20 December 2022, 44 met the inclusion criteria and were included in the review. Data on demographics, clinical features, laboratory findings, treatment, and outcomes were extracted. Results: The median age of 7297 MIS-C patients was 8.6 years, with 59.2% being male. The most common symptoms were fever (98.7%), rash (55.2%), and conjunctivitis (52.8%). Obesity (27.1%) was the most prevalent comorbidity. Fifty percent of patients were admitted to pediatric intensive care; 631 received inotropes, and 374 required mechanical ventilation. Over 80% received IV immunoglobulin, and 77% received corticosteroids. Abnormal echocardiograms occurred in 77.5% of cases, with coronary artery aneurysms present in 18.5%. Most patients recovered, with a reported mortality rate of 1.7%. Conclusion: Despite the limitations, our systematic review provides valuable insights into the characteristics and management of MIS-C based on existing global literature. While a large number of patients required intensive care and various therapeutic interventions, favorable short-term outcomes were demonstrated in the majority of patients, with notably low mortality rates.

SARS-CoV-2 parental vaccination and risk of multisystem inflammatory syndrome in children: a single-center retrospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually causes a mild disease in children and the most serious consequence is multisystem inflammatory syndrome in children (MIS-C). Currently, there are no data about the protective role of vaccination performed by parents on children regarding the development of MIS-C. The aim of our study is to establish whether parental vaccination is related to MIS-C and the protective value of SARS-CoV-2 vaccination performed by parents against the occurrence of MIS-C in their children. Our retrospective single center study included 124 patients aged 1 month to 18 years admitted to emergency department from April 2020 to March 2022 for coronavirus disease 2019 disease. Parental vaccination was negatively correlated with the development of MIS-C: 4% of patients with both parents vaccinated developed MIS-C, while patients with no parent vaccinated to have developed MIS-C were 20%. Parental vaccination could be an important factor influencing the course of the disease and reduces the probability that a child would develop MIS-C by 83% if both parents vaccinated.

Multisystem Inflammatory Syndrome in children at Sohag University Hospital

Multisystem Inflammatory Syndrome in children at Sohag University Hospital

Coronavirus Disease 2019 and Skin: A Retrospective Analysis

Abstract Introduction: Coronavirus disease 2019 (COVID-19), a unique viral infection causing multiorgan failure, can lead to diverse dermatological manifestations, unlike other viral exanthems. There is a scarcity of Indian literature describing these manifestations. Aims and Objectives: To study the dermatological manifestations due to COVID-19 infection. Materials and Methods: It was a retrospective analysis (6 month) of patients with dermatological manifestations related to COVID-19 infection. Medical records were evaluated with respect to demography, detailed clinical presentations, real-time reverse transcription–polymerase chain reaction/rapid antigen test positivity, and related investigations. Statistical Analysis: It was done using proportion, mean, and percentages. Results: A total of 76 cases were recruited. Out of the 76 COVID-19-related cases, there were 67 diagnosed and 9 suspected cases (later came positive). The overall female predominance (n = 69) was observed. The most common age affected was 31-40 years. The most common presentation during prodromal, acute, and postacute phases was urticaria. Other manifestations were chilblain-like, varicella-like, pityriasis rosea-like, erythema multiforme-like, petechial rash, multisystemic inflammatory syndrome in children and confirmed cases of mucormycosis seen with cutaneous manifestation. Conclusion: Our study highlights the need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in patients presenting with rash in otherwise asymptomatic individuals having contact with confirmed case and when associated with systemic symptoms. Dermatological manifestations may play an important role in identifying cases early and serve as an important proxy in managing further spread of this disease in the midst of the global pandemic. Urticaria with fever has diagnostic significance since this combination can be a symptom of an otherwise not confirmed SARS-CoV-2 infection.

Declining Incidence of Kawasaki Disease During the COVID-19 Pandemic: A Time Series Analysis.

In 2020, Taiwan experienced a dramatic disruption of daily life due to measures aimed at limiting the spread of coronavirus disease 2019 (COVID-19), although domestic COVID-19 cases were extremely rare. This provided a chance to investigate the change of incidence and possible triggers of Kawasaki disease (KD) without the interference of multisystem inflammatory syndrome in children. This population-based study used Taiwan's National Health Insurance Research Database. To detect the change in KD incidence in children less than 6 years old during the period of social distancing policy in 2020, the autoregressive integrated moving average model was used based on seasonal variation and the increasing trend of KD incidence over the past 10 years. The trends in population mobility and common infectious diseases were also analyzed to observe their effects on KD incidence. The predicted monthly incidence [95% confidence interval (CI)] of KD in April, May and June 2020 were 5.26 (3.58-6.94), 5.45 (3.70-7.20) and 5.41 (3.61-7.21) per 100,000 person-months. The actual observed incidences were 2.41, 2.67 and 2.60 per 100,000 person-months, respectively, representing a 51.2%, 51.0% and 51.9% reduction in incident rates in the 3-month period of stringent COVID-19 mitigation measures. The trend was not proportionate to the profound decline of common infectious cases. KD incidence decreased by approximately 50% during the period of stringent COVID-19 mitigation measures in 2020 in Taiwan. Human-to-human contact may be a potential KD trigger, but there are likely other contributing factors aside from infection.

One- and Two-year Multidisciplinary Follow-Up of MIS-C at a Tertiary Hospital: A Retrospective Cohort Study.

Although 6-month follow-up of patients with multisystem inflammatory syndrome in children (MIS-C) was reassuring, there is scant data on long-term sequelae, including whether changing variants affect clinical severity and outcomes. Children (<18 years of age) admitted to Great Ormond Street Hospital between April 4, 2020, and January 2023, meeting diagnostic criteria for MIS-C were included. Admission and follow-up data were categorized by the predominant SARS-CoV-2 circulating variant in the United Kingdom. One hundred and sixty children [median age, 10.1 (interquartile range, 7.9-12.6) years] were included. There was no difference in the time of symptom onset to diagnosis between waves ( P =0.23) or hospitalization days across all waves ( P =0.32). Inflammatory markers were normal for up to 2 years in all patients except one. Eleven patients (6.9%) remain in follow-up: cardiology (n=5), gastroenterology (n=5) and nephrology (n=1). The main self-reported symptoms at 2 years were abdominal pain (n=5) and myalgia (n=2). Fatigue was present in approximately a quarter of patients at admission; this reduced to 14 (9%), (2%) and 1 (2%) at 6-month, 1-year and 2-year follow-ups, respectively. Chronic fatigue or long-COVID symptomatology was rare (n=1) even with high rates of concurrent Epstein-Barr virus positivity (49/134). All patients had sustained neurological recovery with no new neurological pathology observed. Patients with MIS-C have a sustained recovery, which is reassuring for positive long-term outcomes. Across waves, time from symptom onset to diagnosis and treatment, symptomatology and length of stay were similar. Sustained recovery is reassuring for clinicians and parents alike. Differentiating long-COVID symptomatology from that of MIS-C is important in formulating an individualized treatment plan.

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

BackgroundThe innate immunity acts during the early phases of infection and its failure in response to a multilayer network of co-infections is cause of immune system dysregulation. Epidemiological SARS-CoV-2 infections data, show that Influenza Virus (FLU-A-B-C) and Respiratory Syncytial Virus (RSV) are co-habiting those respiratory traits. These viruses, especially in children (mostly affected by ‘multi-system inflammatory syndrome in children’ [MIS-C] and the winter pandemic FLU), in the aged population, and in ‘fragile’ patients are causing alteration in immune response. Then, bacterial and fungal pathogens are also co-habiting the upper respiratory traits (e.g., Staphylococcus aureus and Candida albicans), thus contributing to morbidity in those COVID-19 affected patients.MethodsLiquid chromatography coupled with high-resolution mass spectrometry using the quadrupole orbital ion trap analyser (i.e., UHPLC-Q-Orbitrap HRMS) was adopted to measure the polyphenols content of a new nutraceutical formula (Solution-3). Viral infections with SARS-CoV-2 (EG.5), FLU-A and RSV-A viruses (as performed in BLS3 authorised laboratory) and real time RT-PCR (qPCR) assay were used to test the antiviral action of the nutraceutical formula. Dilution susceptibility tests have been used to estimate the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively) of Solution-3 on a variety of microorganisms belonging to Gram positive/ negative bacteria and fungi. Transcriptomic data analyses and functional genomics (i.e., RNAseq and data mining), coupled to qPCR and ELISA assays have been used to investigate the mechanisms of action of the nutraceutical formula on those processes involved in innate immune response.ResultsHere, we have tested the combination of natural products containing higher amounts of polyphenols (i.e., propolis, Verbascum thapsus L., and Thymus vulgaris L.), together with the inorganic long chain polyphosphates ‘polyPs’ with antiviral, antibacterial, and antifungal behaviours, against SARS-CoV-2, FLU-A, RSV-A, Gram positive/ negative bacteria and fungi (i.e., Candida albicans). These components synergistically exert an immunomodulatory action by enhancing those processes involved in innate immune response (e.g., cytokines: IFNγ, TNFα, IL-10, IL-6/12; chemokines: CXCL1; antimicrobial peptides: HBD-2, LL-37; complement system: C3).ConclusionThe prophylactic antimicrobial success of this nutraceutical formula against SARS-CoV-2, FLU-A and RSV-A viruses, together with the common bacteria and fungi co-infections as present in human oral cavity, is expected to be valuable.

МУЛЬТИСИСТЕМНЫЙ ВОСПАЛИТЕЛЬНЫЙ СИНДРОМ, АССОЦИИРОВАННЫЙ С COVID-19 У ДЕТЕЙ, ОСЛОЖНЕННЫЙ ВЕНОЗНЫМИ И АРТЕРИАЛЬНЫМИ ТРОМБОЗАМИ: СЕРИЯ КЛИНИЧЕСКИХ НАБЛЮДЕНИЙ

SARS-CoV-2 causative agent may result in adulthood in hyperinflammatory syndrome and cytokine storm in some patients leading to the microvascular bed thromboses as well as those of large venous and arterial vessels. In the COVID-19 critical form, multisystem inflammatory syndrome in children (MIS-C), thromboses are less common. Authors represent a series of 8 patients’ cases with both thromboses and MIS-C associated with COVID-19 of different localization hospitalized in Nov. 2020-Nov. 2022 aged 4 months to 17 years old (Me 7.5 y/o): 4 aged 4 m/o to 5 y/o and 4 aged 8 to 17 y/o; 6 boys/2 girls. The incidence of thromboses was 13.3% (8/60 pediatric patients with MIS-C); venous thrombosis occurred in 6 (10% of 60), arterial thrombosis in 4 (6.6%), large cerebral vessels thrombosis coupled with the development of bilateral stroke occurred in 2 (3.3%), secondary thrombotic microangiopathy (TMA) in 3 (5%), distal gangrene in a single case (1.7%) and the cerebral venous sinus thrombosis in a single case (1.7%) as well. Treatment was carried out with anticoagulants, aspirin, immunomodulators (intravenous immunoglobulin, glucocorticosteroids, genetically engineered biological drugs). One of 8 patients with thromboses had died from pulmonary embolism (1.7% among all 60 patients with MIS-C), 6 of the 7 survivors continue to be followed up without complications and a single patient continues to have residual severe neurological deficits. Conclusion: venous thrombosis, secondary TMA and large cerebral arteries thrombosis predominated. Treatment of thrombosis with unfractionated heparin intravenously by continuous infusion with a transition to low molecular weight heparins against the background of pathogenetic therapy for MIS-C with immunomodulators was effective in most patients. Acetylsalicylic acid was used in 3 (with coronary dilatation and/or absence of severe thrombocytopenia). Risk factors for thromboses were male gender, severe congenital underlying diseases.

Are Steroids Always Necessary in Multisystem Inflammatory Syndrome in Children (MIS-C)?

Are Steroids Always Necessary in Multisystem Inflammatory Syndrome in Children (MIS-C)?

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

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

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. To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. 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. Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. 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. 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. 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.

Effectiveness of nirmatrelvir/ritonavir in children and adolescents aged 12–17 years following SARS-CoV-2 Omicron infection: A target trial emulation

Currently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection.

Evolution of the Antigenic Landscape in Children and Young Adults with COVID-19 and MIS-C

There is minimal knowledge regarding the durability of neutralization capacity and level of binding antibody generated against the highly transmissible circulating Omicron subvariants following SARS-CoV-2 infection in children with acute COVID-19 and those diagnosed with multisystem inflammatory syndrome in children (MIS-C) in the absence of vaccination. In this study, SARS-CoV-2 neutralization titers against the ancestral strain (WA1) and Omicron sublineages were evaluated in unvaccinated children admitted for COVID-19 (n = 32) and MIS-C (n = 32) at the time of hospitalization (baseline) and at six to eight weeks post-discharge (follow-up) between 1 April 2020, and 1 September 2022. In addition, antibody binding to the spike receptor binding domain (RBD) from WA1, BA.1, BA.2.75, and BA.4/BA.5 was determined using surface plasmon resonance (SPR). At baseline, the children with MIS-C demonstrated two-fold to three-fold higher binding and neutralizing antibodies against ancestral WA1 compared to those with COVID-19. Importantly, in children with COVID-19, the virus neutralization titers against the Omicron subvariants at six to eight weeks post-discharge reached the same level as those with MIS-C had at baseline but were higher than titers at 6–8 weeks post-discharge for MIS-C cases. Cross-neutralization capacity against recently emerged Omicron BQ.1, BQ.1.1, and XBB.1 variants was very low in children with either COVID-19 or MIS-C at all time points. These findings about post-infection immunity in children with either COVID-19 or MIS-C suggest the need for vaccinations in children with prior COVID-19 or MIS-C to provide effective protection from emerging and circulating SARS-CoV-2 variants.

An epidemiological study of multisystem inflammatory syndrome in children (MIS-C) and young adults among COVID-19-positive patients - data from National Inpatient Sample database.

During the pandemic of COVID-19, a novel atypical set of clinical findings was seen among several children with recent or current exposure to the virus. It was termed the "multisystem inflammatory syndrome in children" (MIS-C). Our study used the 2021 National Inpatient Sample to study the associations of sex, race, and age with the incidence of MIS-C among COVID-19-positive children. Out of 69,440 COVID-19-positive children, 2,790 (4.0%) reported MIS-C. The incidence of MIS-C was highest among those aged 8 years old (17,130 MIS-C cases per 100,000 COVID-19 patients), Asian or Pacific Islanders (API) (5,346 MIS-C per 100,000 COVID-19 cases), and males (4,734 cases per 100,000 COVID-19 cases). Furthermore, 7.9% of MIS-C cases met the classification of Kawasaki disease.

Updates on postinfectious skin rashes in pediatric dermatology.

This review provides updates on postinfectious skin rashes in the pediatric population from recently published literature. The COVID-19 pandemic and its sequelae remain a focus of research on pediatric infectious skin rashes. Multisystem inflammatory syndrome in children (MIS-C) and reactive infectious mucocutaneous eruption (RIME) are common complications of infection with SARS-COV-2 in the pediatric population. Most cases of MIS-C show low mortality and suggest mucocutaneous symptoms do not correlate with COVID-19 disease severity. Cases of papular acrodermatitis of childhood, also known as Gianotti-Crosti, have also been reported in association with SARS-COV-2, and can present similarly in reaction to other viral infection like molluscum contagiosum, known as a Gianotti-Crosti syndrome-like reaction (GCLR). Other relevant studies on postinfectious skin rashes include updates on the management of staphylococcal scalded skin syndrome (SSSS), with newer evidence advocating for beta-lactam monotherapy without clindamycin and reduced ancillary testing. Finally, the emergence of antifungal resistance due to Trichophyton indotinae is a growing global health concern emphasizing the need for improved antifungal stewardship. It is prudent for clinicians to be informed of both common and rare diagnoses that have emerged more recently in association with the COVID-19 pandemic, in addition to other diseases with newer evidence-based recommendations to guide management.