Evaluation of platelet indices as markers of tuberculosis among children in India.

Children with tuberculosis have increased platelet count and platelet/lymphocyte ratio along with decreased mean platelet volume, suggesting that these indices may be useful as adjunct tools in diagnosis of paediatric tuberculosis https://bit.ly/3Ga4AWT.

Elucidating systemic immune responses to acute and convalescent SARS-CoV-2 infection in children and elderly individuals.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a causative pathogen of the COVID-19 pandemic, affects all age groups. However, various studies have shown that COVID-19 presentation and severity vary considerably with age. We, therefore, wanted to examine the differences between the immune responses of children with COVID-19 and elderly COVID-19 individuals. METHODS: We analyzed cytokines, chemokines, growth factors, and acute phase proteins in acute and convalescent COVID-19 children and the elderly with acute and convalescent COVID-19. RESULTS: We show that most of the pro-inflammatory cytokines (interferon [IFN]γ, interleukin [IL]-2, tumor necrosis factor-α [TNFα], IL-1α, IFNα, IFNß, IL-6, IL-12, IL-3, IL-7, IL-1Ra, IL-13, and IL-10), chemokines (CCL4, CCL11, CCL19, CXCL1, CXCL2, CXCL8, and CXL10), growth factors (vascular endothelial growth factor and CD40L) and acute phase proteins (C-reactive protein, serum amyloid P, and haptoglobin) were decreased in children with acute COVID 19 as compared with elderly individuals. In contrast, children with acute COVID-19 exhibited elevated levels of cytokines- IL-1ß, IL-33, IL-4, IL-5, and IL-25, growth factors-fibroblast growth factor-2, platelet- derived growth factors-BB, and transforming growth factorα as compared with elderly individuals. Similar, differences were manifest in children and elderly with convalescent COVID-19. CONCLUSION: Thus, COVID-19 children are characterized by distinct cytokine/chemokine/growth factor/acute phase protein markers that are markedly different from elderly COVID-19 individuals.

Sex-specific differences in systemic immune responses in MIS-C children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease.

Multisystem inflammatory syndrome in children characterized by enhanced antigen-specific T-cell expression of cytokines and its reversal following recovery.

Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied. Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections. Whole blood was stimulated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antigens and flow cytometry was performed to examine CD4+ and CD8+ T-cell responses. Results: Children with MIS had higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with COVID-19 and/or other infections. Children with COVID-19 also exhibited higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with other infections. At 6-9 months following treatment and recovery, this enhanced response against SARS-CoV-2 antigens was down modulated in children with MIS. Conclusion: Our study, therefore, provides evidence of enhanced activation of CD4+ and CD8+ T-cell responses in children with MIS and reversal following recovery.

Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. METHODS: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. RESULTS: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1ß, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. CONCLUSIONS: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.

Alterations of adipokines, pancreatic hormones and incretins in acute and convalescent COVID-19 children.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes. METHODS: We wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19. RESULTS: Acute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines. CONCLUSION: Children with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.

Levels of Complement Components in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a severe and unrestrained inflammatory response with multiorgan involvement, which occurs within a few weeks following the resolution of acute SARS-CoV-2 infection. The complement system is a vital part of the innate immune system and plays a role in COVID-19 pathogenesis. Objective: To examine and compare the levels of complement components and regulators along with complement activation products in the different clinical spectrum of children with SARS-CoV-2 and a control group. Design, Setting, and Participants: This cross-sectional study analyzed children with MIS-C admitted to a single hospital in India from June through September 2020. Eligible participants were children who were hospitalized of either sex, aged 1 to 18 years. Data were analyzed August 2022. Measures: Levels of complement components and regulators along with complement activation products in all the groups of children. Mann-Whitney U test and Kruskal-Wallis analysis were used to compare the complement component levels, and Spearman rank correlation analysis was used to describe the association between complement components and laboratory and biochemical parameters. Results: A total 145 children were included (median age, 5 years [range, 1 month-17 years); 84 [58%] male): 44 children with MIS-C, 33 with acute COVID-19 (reverse transcriptase-polymerase chain reaction [RT-PCR] positive), 47 with convalescent COVID-19 (immunoglobulin G-positive non-MIS-C) and 21 children for a control group (both serology and RT-PCR negative). Children with MIS-C and COVID-19 had higher levels of C1q (geometric mean [SD]: MIS-C, 61.5 [18.5] ng/mL; acute COVID-19, 56.9 [18.6] ng/mL; controls, 24.1 [3.3] ng/mL), C2 (MIS-C, 605.8 [219.7] ng/mL; acute COVID-19, 606.4 [167.7] ng/mL; controls, 255.9 [73.3] ng/mL), C3 (MIS-C, 318.2 [70.7] ng/mL; acute COVID-19, 237.7 [61.8] ng/mL; controls, 123.4 [15.7] ng/mL), C4b (MIS-C, 712.4 ng/mL; acute COVID-19, 640.7 ng/mL; controls, 351.5 ng/mL), C5 (MIS-C, 1487 ng/mL; acute COVID-19, 1364 ng/mL; controls, 561.9 ng/mL), C5a, (MIS-C, 2614.0 [336.2] ng/mL; acute COVID-19, 1826.0 [541.0] ng/mL; controls, 462.5 [132.4] ng/mL), C3b/iC3b (MIS-C, 3971.0 [635.1] ng/mL; acute COVID-19, 3702.0 [653.9] ng/mL; controls, 2039.0 [344.5] ng/mL), and factor B (MIS-C, 47.6 [7.8] ng/mL; acute COVID-19, 44.6 [6.3] ng/mL; controls, 27.5 [5.0] ng/mL), factor D (MIS-C, 44.0 [17.2] ng/mL; acute COVID-19, 33.8 [18.4] ng/mL; controls, 21.3 [6.1] ng/mL), and factor H (MIS-C, 53.1 [4.0] ng/mL; acute COVID-19, 50.8 [5.7] ng/mL; controls, 43.6 [3.8] ng/mL) in comparison with convalescent and control children. In addition, children with MIS-C had significantly elevated levels of C3 (318.2 [70.7] ng/mL vs 237.7 [61.8] ng/mL), C5a (2614 [336.2] ng/mL vs 1826 [541.0] ng/mL), and mannose-binding lectin (79.4 [12.4] ng/mL vs 69.6 [14.7] ng/mL) in comparison to children with acute COVID-19. Levels of some of these analytes at admission (ie, pretreatment) were more elevated in children with MIS-C who needed pediatric intensive care unit (PICU) support as compared with those who did not require PICU support, and in children with COVID-19 who developed moderate to severe disease compared with those who developed mild disease. Overall, MIS-C and acute COVID-19 were associated with the hyperactivation of complement components and complement regulators. Conclusions and Relevance: In this cross-sectional study, the complement system was associated with the pathogenesis of MIS-C and COVID-19 in children; complement inhibition could be further explored as a potential treatment option.

Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children.

Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. Methods: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). Results: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84-100% and specificity 80-100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. Discussion: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.

Unique cellular immune signatures of multisystem inflammatory syndrome in children.

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.

Comparison of two mycobacterial strains in performance of the whole blood mycobacterial growth inhibition assay in Indian children.

A major challenge in tuberculosis is identifying correlates of a protective immune response. The Mycobacterial Growth Inhibition Assay (MGIA) is a functional assay providing an integrated measure of the host immune response to mycobacteria. However, its feasibility is limited by reliance on biosafety level 3 facilities, and its performance has not been widely evaluated in TB-endemic settings. Here, we compared two mycobacterial strains (M. tuberculosis H37Rv versus attenuated M. bovis BCG) in the performance of whole-blood MGIA in 30 TB-exposed children (median age 2 years) in Chennai, India. The time-to-positivity in both assays was similar (5.7 days vs 6 days) and the mycobacterial growth of M. tuberculosis H37Rv and M. bovis BCG were correlated (r = 0.64, p<0.0001). In Bland-Altman analysis, the bias was -0.54 days (95% limit of agreement -2.08, 0.99). Collectively, our results indicate that M. tuberculosis H37Rv can be substituted with the less virulent M. bovis BCG strain to improve feasibility of the MGIA assay, particularly in low-income settings.

Enhanced Severe Acute Respiratory Syndrome Coronavirus 2 Antigen-Specific Systemic Immune Responses in Multisystem Inflammatory Syndrome in Children and Reversal After Recovery.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. RESULTS: MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis based on these cytokines and chemokines could clearly distinguish MIS-C from both COVID-19 and other infections. In addition, these responses were significantly diminished and normalized 6-9 months after recovery. CONCLUSIONS: Our data suggest that MIS-C is characterized by an enhanced production of cytokines and chemokines that may be associated with disease pathogenesis.

Systemic Inflammation and Microbial Translocation Are Characteristic Features of SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that can result in increased morbidity and mortality. The inflammatory underpinnings of MIS-C have not been examined in detail. METHODS: We examined the plasma levels of acute phase proteins and microbial translocation markers in children with MIS-C, children with acute coronavirus disease 2019 (COVID-19) infection, SARS-CoV-2-seropositive children, and controls. RESULTS: MIS-C children exhibited significantly higher levels of C-reactive protein (CRP), alpha2 macroglobulin (α2M), serum amyloid P (SAP), lipopolysaccharide (LPS), sCD14, and LPS binding protein (LBP) and significantly lower levels of haptoglobin (Hp) in comparison with seropositive, control, and/or COVID-19 children. In addition, COVID-19 children exhibited significantly higher levels of most of the above markers in comparison with seropositive and control children. Principal component analysis using a set of these markers could clearly discriminate MIS-C and COVID-19 from seropositive and control children. MIS-C children requiring pediatric intensive care unit admission and COVID-19 children with severe disease had higher levels of CRP, SAP, and/or sCD14 at admission. CONCLUSIONS: Our study describes the role of systemic inflammation and microbial translocation markers in children with MIS-C and COVID-19 and therefore helps in advancing our understanding of the pathogenesis of different presentations of SARS-CoV-2 infection in children.

Plasma biomarker profiling of PIMS-TS, COVID-19 and SARS-CoV2 seropositive children - a cross-sectional observational study from southern India.

BACKGROUND: SARS-CoV-2 infection in children can present with varied clinical phenotypes and understanding the pathogenesis is essential, to inform about the clinical trajectory and management. METHODS: We performed a multiplex immune assay analysis and compared the plasma biomarkers of Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), acute COVID-19 infection (COVID-19), SARS-CoV-2 seropositive and control children admitted to a tertiary care children's hospital in Chennai, India. Pro-inflammatory cytokines, chemokines and growth factors were correlated with SARS-CoV-2 clinical phenotypes. FINDINGS: PIMS-TS children had significantly elevated levels of cytokines, IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNß, IL-6, IL-15, IL-17A, GM-CSF, IL-10, IL-33 and IL-Ra; elevated chemokines, CCL2, CCL19, CCL20 and CXCL10 and elevated VEGF, Granzyme B and PDL-1 in comparison to COVID-19, seropositive and controls. COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNß, IL-6, IL-17A, IL-10, CCL2, CCL5, CCL11, CXCL10 and VEGF in comparison to seropositive and/or controls. Similarly, seropositive children had elevated levels of IFNγ, IL-2, IL-1α, IFNß, IL-17A, IL-10, CCL5 and CXCL10 in comparison to control children. Plasma biomarkers in PIMS-TS and COVID-19 children showed a positive correlation with CRP and a negative correlation with the lymphocyte count and sodium levels. INTERPRETATION: We describe a comprehensive plasma biomarker profile of children with different clinical spectrum of SARS-CoV-2 infection from a low- and middle-income country (LMIC) and observed that PIMS-TS is a distinct and unique immunopathogenic paediatric illness related to SARS-CoV-2 presenting with cytokine storm different from acute COVID-19 infection and other hyperinflammatory conditions.

Correlation of SARS-CoV-2 Serology and Clinical Phenotype Amongst Hospitalised Children in a Tertiary Children's Hospital in India.

INTRODUCTION: Children usually present with minimal or no symptoms of COVID-19 infection. Antibody responses to SARS-CoV-2 in children from low- and middle-income countries (LMIC) have not been well described. We describe the prevalence of anti-SARS-CoV-2 antibodies and clinical phenotype of seropositive children admitted to a tertiary children's hospital in South India. METHODS: To determine the seropositivity and describe the clinical characteristics of COVID-19 infection amongst hospitalised children, we performed a prospective clinical data collection and blood sampling of children admitted to Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India over 4 months of the COVID-19 pandemic. In seropositive children, we compared antibody titres between children with and without PIMS-TS. RESULTS: Of 463 children, 91 (19.6%) were seropositive. The median (range) age of seropositive children was 5 years (1 month-17 years). Clinical presentation was consistent with Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) in 48% (44/91) of seropositive children. The median (range) antibody titre was 54.8 (11.1-170.9) AU/ml among all seropositive children. The median antibody titre among the children with PIMS-TS (60.3 AU/mL) was significantly (p = 0.01) higher when compared to the children without PIMS-TS (54.8 AU/mL). CONCLUSION: We describe the antibody responses to SARS-CoV-2 amongst hospitalised children in a LMIC tertiary children's hospital. Almost half of the seropositive children had PIMS-TS. Antibody levels may be helpful in the diagnosis and disease stratification of PIMS-TS. LAY SUMMARY: Children usually present with minimal or no symptoms of COVID-19 infection. However, Multisystem Inflammatory Syndrome in Children (MIS-C) or Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) has emerged as a distinctive paediatric illness related to SARS-CoV-2. Recently, antibody testing for SARS-CoV-2 is being used increasingly as a diagnostic test for PIMS-TS. However, data on the antibody responses to SARS-CoV-2 in children are sparse. We, therefore, attempted to identify the seropositivity and describe the clinical spectrum of COVID-19 infection amongst infants and children getting hospitalised in a children's hospital in south India. Nearly one-fifth of the hospitalised children tested serology positive over 4 months. Antibody levels in children with PIMS-TS were significantly higher in comparison to the other two groups (acute COVID-19 infection and children without PIMS-TS). Results from our study suggest that all children are at risk of COVID-19 infection though they may present with mild illness or no symptoms. We also observed that antibody testing may have a possible role in diagnosis of PIMS-TS.

Epidemiological and Clinical Profile of Pediatric Inflammatory Multisystem Syndrome - Temporally Associated with SARS-CoV-2 (PIMS-TS) in Indian Children.

Background: We describe the demographic, clinical and labo-ratory findings along with the treatment and outcomes among children meeting the case definition of Pediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We analyzed the clinical and laboratory findings of children who presented with PIMS-TS during an 8-week period from May 4, 2020 to July 8, 2020. RESULTS: We report 19 children with a median age of 6 year (IQR: 13 months-16 years), who met the case definition of PIMS-TS. All of them presented with fever. Multi organ involvement (79%), mucocutaneous involvement (74%), cardiovascular symptoms (63%) and gastrointestinal symptoms (42%) were the other features. Elevated levels of C-reactive protein was found in all of them and the majority of them had evidence of coagulopathy; intensive care admissions were needed in 12 (63%) and vasoactive medications were given to 6 (31.5%) children. There were no deaths. CONCLUSION: Children with PIMS-TS present with a wide range of signs and symptoms. Fewer children in this series had coronary artery abnormalities, and there was a low incidence of RT-PCR positivity with high presence of SARS-CoV-2 antibodies.

Pediatric Resuscitation: Do We Maintain Adequate Skills?

Adequate skills and knowledge is necessary in pediatric cardiopulmonary resuscitation. We conducted a study to evaluate the current status of resuscitation knowledge and skills among the pediatric medical and nursing staff at the Royal London Hospital, London.

Paediatric electronic infusion calculator: An intervention to eliminate infusion errors in paediatric critical care.

INTRODUCTION: Medication errors, including infusion prescription errors are a major public health concern, especially in paediatric patients. There is some evidence that electronic or web-based calculators could minimise these errors. AIMS: To evaluate the impact of an electronic infusion calculator on the frequency of infusion errors in the Paediatric Critical Care Unit of The Royal London Hospital, London, United Kingdom. METHOD: We devised an electronic infusion calculator that calculates the appropriate concentration, rate and dose for the selected medication based on the recorded weight and age of the child and then prints into a valid prescription chart. Electronic infusion calculator was implemented from April 2015 in Paediatric Critical Care Unit. A prospective study, five months before and five months after implementation of electronic infusion calculator, was conducted. Data on the following variables were collected onto a proforma: medication dose, infusion rate, volume, concentration, diluent, legibility, and missing or incorrect patient details. RESULTS: A total of 132 handwritten prescriptions were reviewed prior to electronic infusion calculator implementation and 119 electronic infusion calculator prescriptions were reviewed after electronic infusion calculator implementation. Handwritten prescriptions had higher error rate (32.6%) as compared to electronic infusion calculator prescriptions (<1%) with a p < 0.001. Electronic infusion calculator prescriptions had no errors on dose, volume and rate calculation as compared to handwritten prescriptions, hence warranting very few pharmacy interventions. CONCLUSIONS: Use of electronic infusion calculator for infusion prescription significantly reduced the total number of infusion prescribing errors in Paediatric Critical Care Unit and has enabled more efficient use of medical and pharmacy time resources.

Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. AIM: To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. METHODS: All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. RESULTS: Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. CONCLUSIONS: Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain.