Abstract Objective To describe the clinical characteristics, laboratory parameters, treatment, and predictors of an unfavorable outcome of critically ill children with SARS-CoV-2 infection. Method This was a prospective observational study performed in a pediatric intensive care unit (PICU) of a tertiary care COVID referral hospital among critically ill children in the age group 1 month - 12 years admitted due to SARS-CoV-2 infection from June to December 2020. Demographic, clinical profile, pSOFA and PRISM III scores, laboratory parameters, treatment, and outcomes of the patients were recorded. Children who had a prolonged PICU stay (>14 days) or died were compared with those who were discharged from PICU within 14 days to assess predictors of unfavorable outcomes. Results PICU admission rate among hospitalized SARS-CoV-2 infected children was 22.1% (92/416). Infants comprised the majority of the ICU population. Invasive mechanical ventilation and inotropic support were required for 28.3% and 37% of patients, respectively. Remdesivir, IVIg, and steroids were administered to 15.2%, 26.1%, and 54.3% of the subjects, respectively. The mortality rate was 7.6 %. MIS-C patients were older, less comorbid, and required less ventilator support but more inotrope support than acute severe COVID-19 patients. Predictors of unfavorable outcomes were age < 1 year, fever duration > 5 days, respiratory distress, shock, comorbidity, elevated CRP (> 50 mg/L), procalcitonin (> 6 ng/L), D-dimer (> 6 µg/L) and arterial lactate (> 2 mmol/L). Conclusion Critically ill children with unfavorable outcomes were predominantly infants, comorbid, prolonged fever, respiratory distress, shock and elevated inflammatory markers, D-dimer and lactate. These factors may be useful for watchful monitoring and early intervention.

Abstract Background: PGF2α is essential for the induction of the corpus luteum regression which in turn reduces progesterone production. Early growth response (EGR) proteins are Cys2-His2-type zinc-finger transcription factor that are strongly linked to cellular proliferation, survival and apoptosis. Rapid elevation of EGR1 was observed after luteolytic dose of PGF2α. EGR1 is involved in the transactivation of many genes, including TGFβ1, which plays an important role during luteal regression. Methods: The current study was conducted in buffalo luteal cells with the aim to better understand the role of EGR1 in transactivation of TGFβ1 during PGF2α induced luteal regression. Luteal cells from mid stage corpus luteum of buffalo were cultured and treated with different doses of PGF2α for different time durations. Relative expression of mRNAs encoding for enzymes within the progesterone biosynthetic pathway (3βHSD, CYP11A1 and StAR); Caspase 3; AKT were analyzed to confirm the occurrence of luteolytic event. To determine if EGR1 is involved in the PGF2α induced luteal regression via induction of TGFβ1 expression, we knocked out the EGR1 gene by using CRISPR/Cas9. Result: The present experiment determined whether EGR1 protein expression in luteal cells was responsive to PGF2α treatment. Quantification of EGR1 and TGFβ1 mRNA showed significant up regulation in luteal cells of buffalo at 12 h post PGF2α induction. In order to validate the role of PGF2α on stimulating the expression of TGFβ1 by an EGR1 dependent mechanism we knocked out EGR1. The EGR1 ablated luteal cells were stimulated with PGF2α and it was observed that EGR1 KO did not modulate the PGF2α induced expression of TGFβ1. In PGF2α treated EGR1 KO luteal cell, the mRNA expression of Caspase 3 was significantly increased compared to PGF2α treated wild type luteal cells maintained for 12 h. We also studied the influence of EGR1 on steroidogenesis. The EGR1 KO luteal cells with PGF2α treatment showed no substantial difference either in the progesterone concentration or in StAR mRNA expression with PGF2α-treated wild type luteal cells. Conclusion: These results suggest that EGR1 signaling is not the only factor which plays a role in the regulation of PGF2α induced TGFβ1 signaling for luteolysis.