This was a retrospective observational study. The medical records of the patients admitted to the pediatric intensive care unit (PICU) from July to October 2020 were retrieved from the hospitals electronic database and inpatient records after obtaining necessary approval from the institutional review board. The records were analyzed for clinical and laboratory characteristics, treatment modalities and out-comes in PCR-positive and PCR-negative antibody-positive children.

The diagnosis of MIS-C was based on the WHO case definition, as any child with fever for three or more days and any two of the following, i) rash, conjunctivitis and/or mucocutaneous inflammation, ii) hypotension (SBP <5th centile), iii) features of myocardial dysfunction, iv) evidence of coagulopathy, v) acute gastrointestinal problems; and elevated markers of inflammation, with no obvious microbial cause on testing (including negative blood cultures, dengue and scrub typhus serology), and a positive COVID-19 test or contact with a COVID-19 patient [4]. The laboratory parameters that were assessed included ferritin, D-dimer, pro-brain natriuretic peptide BNP, troponin-T, procalcitonin, C-reactive protein (CRP), serum albumin and platelets. Diagnosis of SARS-CoV-2 infection was made by real-time reverse transcription-polymerase chain reaction (RT-PCR) assays done from nasopharyngeal swabs of children at admission. The COVID antibody test was done by rapid antibody tests to SARS-CoV-2 by chemil-uminescent immunoassay (CLIA) by 2 different kits, Siemens S1-RBD rapid antibody test (total or IgG by Siemens Healthineers) with measuring interval/index value 0.05-10 AU/mL and Roche and Abbott-Nucleocapsid (antibody) with cut off index <1 being non-reactive .

All children who were SARS-CoV-2 PCR positive or antibody positive fulfilling the MIS-C criteria were managed as per standard WHO treatment guidelines for critical disease including shock and ARDS (based on PaO2/FiO2 ratio and chest X-ray) [5], and the American College of Rheumatology (ACR) guidance on treatment of MIS-C [6], which included dexamethasone at 0.15 mg/kg/dose once daily and anticoagulant therapy with low molecular weight heparin (LMWH) at a dose of 0.5 mg/kg/dose twice daily in all children with D-dimer >500 ng/mL. Critically ill children on mechanical ventilation received unfractionated heparin at 5-10 units/kg/hour as an intravenous infusion for 24-48 hours till they were stable, which was then changed to LMWH. Intravenous immune globulin (IVIG) at a dose of 2 g/kg over 2 days was given to children with catecholamine-resistant shock and severe left ventricular dysfunction.

Statistical analysis: Statistical analysis was done using SPSS 23.0 (SPSS Inc.). Percentages and mean (standard deviations) were calculated for categorical and continuous variables, respectively. Independent sample t-test was used for comparing the means and two proportions test to compare the proportions between groups.

Over the study period, 415 children were admitted and screened for COVID-19 of whom 215 were admitted to COVID PICU (age range 1 month to 15 years). Thirty-six children (16%) were SARS-CoV-2 PCR positive, of whom 7 (19%) had moderate illness, 5 (14%) had severe and 24 (66%) had critical disease. Of the 24 children with critical disease, 10 (41%) had MIS-C. An additional 7 children with MIS-C were RT-PCR negative but COVID antibody-positive. Three PCR-positive infants aged one month, six months and 11 months had prematurity as a premorbid risk factor, and the 6 month old had also undergone Kasai procedure at 2 months of age for biliary atresia.

Clinical presentations were similar with fever in all and fluid-refractory hypotensive shock in 16 (75% of children being in cold shock) and respiratory distress in 16 children. The comparative clinical features between PCR-positive and PCR-negative antibody positive children are shown in Table I. Additional atypical manifestations seen in 2 children included refractory thrombocytopenia in a one-month-old infant and CNS stroke in a 6-year-old who had received steroids prior to admission and did not have respiratory distress or hypotensive shock at admission.