Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Covid-19 - Single-Center Experience.

OBJECTIVES: To describe the clinical presentation, phenotype and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (Covid-19) from a tertiary care center in southern India. METHODS: 257 children fulfilling the inclusion criteria of MIS-C were prospectively enrolled from June, 2020 to March, 2022. RESULTS: Median (range) age at presentation was 6 year (35 day to 12 years). Presenting features were fever (98%), vomiting (75.8%), red eyes (63%), rashes (49%), pain abdomen (49%), shock (45.9%), lymphopenia (73%, thrombocytopenia (58.3%) and anemia (45%). 103 (39.7%) children required intensive care admission. Shock phenotype, Kawasaki-like phenotype and no specific phenotype were diagnosed in 45.9%, 44.4%, and 36.6% children, respectively. Left ventricular dysfunction (30.3%), acute kidney injury (13%), acute liver failure (17.4%), and hemophagolymphohistiocytosis (HLH) (13.6%) were the major system involvement in MIS-C. Mitral regurgitation (P=0.029), hyperechogenic coronaries (P=0.006), Left ventricular dysfunction (P=0.001) and low ejection fraction (P=0.007) were significantly associated with shock. Overall mortality was 11.7%. CONCLUSION: Kawasaki-like and shock-like presentation were common in MIS-C. Coronary abnormalities were seen in 118 (45.9%) children. Children with acute kidney injury, HLH, need for mechanical ventilation, and echocardiogram evidence of mitral regurgitation in MIS-C have a poor outcome.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2.

OBJECTIVES: To know the clinical presentation and outcome of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV- 2 (PIMS-TS) at a pediatric tertiary care center in Chennai. METHODS: Clinical and biochemical parameters of 65 children with PIMS-TS treated between July and October 2020 were studied. All children had their COVID RT-PCR and IgG COVID antibodies tests done. RESULTS: Mean age of the study group was 5.65 ± 3.68 y. Fever with red eyes, rash, vomiting, abdominal pain, and shock were common presenting features. Sixty percent of the study group had Kawasaki/incomplete Kawasaki features. Sixty-seven percent of the study group had coronary dilatation, 41% presented with shock, and 25% had left ventricular dysfunction. Coronary aneurysms were documented in 58% of the study group (z score more than 2.5). Respiratory presentation with pneumonia was seen in 10%. Four children presented with acute abdomen. Acute kidney injury, acute liver failure, hemolysis, pancytopenia, macrophage activation syndrome, encephalopathy, and multiorgan dysfunction syndrome (MODS) were other features. Forty-three percent required noninvasive oxygen support and 15.4% required mechanical ventilation. Intravenous immunoglobulin (73.8%) and methylprednisolone (49.8%) were used for therapy. Mortality in the study was 6%, which was due to MODS. CONCLUSIONS: Acute febrile illness with mucocutaneous and gastrointestinal manifestations should have PIMS-TS as a possible differential diagnosis and needs evaluation with inflammatory markers and SARS-CoV-2 antibodies.

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis.

BACKGROUND: Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis. METHODS: We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. RESULTS: Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. CONCLUSION: Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.

Tuberculosis preventive treatment should be considered for all household contacts of pulmonary tuberculosis patients in India.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.