Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

A bstract Background Multisystem inflammatory syndrome (MIS) associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2) (MIS-C) in children is being increasingly reported across the world. Materials and methods Children fulfilling the World Health Organization criteria of MIS-C needing pediatric intensive care unit between April 15 and July 26, 2020 were studied. Results There were 21 patients with median age of 7 years [interquartile range (IQR) 1.9–12.1], of which 11 were females. SARS-CoV-2 real-time polymerase chain reaction positive in 8/21 and/or antibody positive 16/21. Fever was present in all patients, and gastrointestinal symptoms being second most frequent (16/21). One child had aplastic anemia, while the rest had no comorbidities. Nearly all presented with shock ( n = 20/21) and 90% needed vasoactive drugs with a median Vasoactive Inotropic Score of 40 (IQR 20–95). Thirteen children needed ventilatory support and one needed peritoneal dialysis. Nine children had left ventricular dysfunction and five had dilatation of coronaries on echocardiography. Inflammatory markers C-reactive protein [98 mg/dL (IQR 89–119)], serum ferritin [710 mg/dL (IQR 422–1,609)], and serum interleukin-6 levels [215 ng/L (IQR 43–527)] were uniformly elevated. Eighteen children received pulse methyl-prednisolone, eleven intravenous immunoglobulins, and four tocilizumab. Eighteen children (86%) were discharged home while three died. Conclusion In our cohort, MIS-C was seen in previously healthy children with fever, gastrointestinal symptoms, and shock. Early and aggressive management of shock and immune modulation with methyl-prednisolone and intravenous immunoglobulin were used. How to cite this article Shobhavat L, Solomon R, Rao S, Bhagat I, Prabhu S, Prabhu S, et al. Multisystem Inflammatory Syndrome in Children: Clinical Features and Management—Intensive Care Experience from a Pediatric Public Hospital in Western India. Indian J Crit Care Med 2020;24(11):1089–1094.

Objective To study clinical characteristics and outcome of children with admitted to a paediatric hospital in Mumbai, India. Method Review of medical records of 969 children admitted between 19 March and 7 August, 2020, to assess the clinico-demographic characteristics, disease severity and factors predicting outcome in COVID-19 children. Variables were compared between children who were previously healthy (Group I) and those with co-morbidity (Group II). Results 123 (71 boys) children with median (IQR) age of 3 (0.7–6) years were admitted, of which 47 (38%) had co-morbidities. 39 (32 %) children required intensive care and 14 (11.4%) died. Male sex, respiratory manifestation, oxygen saturation <94% at admission, mechanical ventilation, inotrope, hospital stay of <10 days were independent predictors of mortality. Oxygen saturation <94% at admission (OR 35.9, 95% CI 1.5–856) and hospital stay <10 days (OR 9.1, 95% CI 1.04–99.1) were significant. Conclusion COVID-19 in children with co-morbidities causes severe disease. Association of mortality with oxygen saturation by pulse oximeter <94% on admission, and hospital stay <10 days, needs further evaluation.

Neonatal data regarding SARS-CoV-2 is sparse from India. On review of hospital records from April- August, 2020, 18/423 (4.25%) neonates were SARS-CoV-2 RT-PCR positive. 15 (83.3%) neonates recovered and 3 (16.6%) succumbed. Only 50% of the positive babies had positive mothers/ caretakers, a contact could not be traced in others.

SARS-CoV-2-related multisystem inflammatory syndrome in an immunocompromised child with leukemiaTo the Editor:associated multisystem inflammatory syndrome in children (MIS-C) is increasingly recognised in children with clinical presentations resembling disorders ranging from toxic shock syndrome to Kawasaki disease. MIS-C is diagnosed in immunocompetent children based on the clinical and laboratory profile of the patient with history or evidence of exposure to the SARS-CoV-2 virus. A high index of suspicion is required for diagnosis of MIS-Cin cancer patients receiving immunosuppressive therapy. We describe the first case of MIS-C in a child receiving significantly immunosuppressive chemotherapy.

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The energy metabolism of myeloid cells depends primarily on glycolysis. 1,5-anhydroglucitol (1,5AG), a natural monosaccharide is erroneously phosphorylated by glucose-phosphorylating enzymes to produce 1,5-anhydroglucitol-6-phosphate (1,5AG6P), a powerful inhibitor of hexokinases. The endoplasmic reticulum transporter (SLC37A4/G6PT) and the phosphatase G6PC3 co-operate to dephosphorylate 1,5AG6P. Failure to eliminate 1,5AG6P is the mechanism of neutrophil dysfunction and death in G6PC3de cient mice. SLGT2-inhibitor reduces 1,5AG level in the blood and restores the neutrophil count in G6PC3-de cient mice. In the investigator-initiated study, a 30 year-old G6PC3-de cient woman with recurrent infections, distressing gastrointestinal symptoms and multi-lineage cytopenia was treated with an SLGT2-inhibitor. A signi cant increase in all the hematopoietic cell lineages and substantial improvement in the quality of life was observed.