Multisystem Inflammatory Syndrome Associated With COVID-19 in Children (MIS-C): A Systematic Review of Studies From India.

BACKGROUND: With wide clinical spectrum, multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children (MIS-C) is a relatively novel condition occurring weeks to months' post SARS-CoV-2 infection. The aim was to systematically review data on clinical features, laboratory parameters and therapeutics of MIS-C from India. Methods: This systematic review was done as per the PRISMA guidelines, and quality assessment was done using NIH tool for case-series. A systematic search through databases yielded studies whose data was pooled to calculate the mean frequencies with standard deviation using GraphPad software. RESULTS: Screening of 2548 articles published till December, 2021, yielded 11 case-series. World Health Organization case definition was used widely. There was a slight preponderance of males (57%), median (IQR) age was 7 (6,7) years, 63% (n=305) required intensive care unit admissions, and mortality rate was 10% (n=261). Clinical features included fever, mucocutaneous features (72%), and gastrointestinal problems (62%) in majority. Widely used treatment was corticosteroids (76%) and intravenous immunoglobulin (62%) with other options depending on patient's state. An increased level of inflammatory markers and derangement in other parameters corroborated with disease status. Kawasaki disease like features, not reported in many studies, ranged from 4-76% of patients. CONCLUSION: MIS-C presents with a wide spectrum clinical features, increased inflammatory markers and managed as per the disease course and presentation. Future studies monitoring the long-term effects of MIS-C are recommended.

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. METHODS: A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. RESULTS: Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. CONCLUSIONS: Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.

HIV infection is associated with a progressive decline of CD4+ T-cell numbers and increase in viral load. To keep the virus replication in check, patients need to take the antiretroviral therapy life-long, which is not without gastrointestinal discomfort. Probiotics have already shown multiple benefits ranging from reduction in diarrhea, nausea and bloating besides replenishment of CD4+ T-cells numbers. Based on this background information, we have compiled the data on probiotics among HIV-infected children. A pooled analysis from randomized clinical trials revealed significant improvement in CD4+ T-cell counts in HIV-infected children without any adverse effects. However, we recommend large and well-designed trials in future that would help in forming a concrete and high quality evidence in this context.