Effectiveness of early Anakinra on cardiac function in children with multisystem inflammatory syndrome of COVID-19: a systematic review.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C. METHODS: A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra's role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements. CONCLUSION: Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra's effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols.

Timing of HIV testing among pregnant and breastfeeding women and risk of mother-to-child HIV transmission in Malawi: a sampling-based cohort study.

INTRODUCTION: Pregnant women living with HIV can achieve viral suppression and prevent HIV mother-to-child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi's PMTCT programme. METHODS: We conducted a two-stage cohort study among mother-infant pairs in 30 randomly selected high-volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log-binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting. RESULTS: Of 822 mother-infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81). CONCLUSIONS: MTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.