Potentially effective drugs for the treatment of COVID-19 in children: a systematic review

IntroductionThe purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. MethodsWe searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. ResultsA total of six cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 37.1% (95%CI, 0.0% to 74.5%) experienced adverse events, 5.9% (95%CI, 1.5% to 10.2%) died, 37.2% (95%CI, 0% to 76.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, the two included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. ConclusionsOverall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

A follow-up study of children infected with SARS-CoV-2 from Western China

BackgroundTo clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. MethodsA total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. ResultsEleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. ConclusionsChildren with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis

BackgroundGlucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited. MethodsWe comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies. ResultsOur search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75, I2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). ConclusionsGlucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.

Health Education for Parents During the COVID-19 OutbreakPublic Health Education for Parents During the Outbreak of COVID-19: A Rapid Review

BackgroundIt is well-known that public health education plays a crucial role in the prevention and control of emerging infectious diseases, but how health providers should advise families and parents to obtain health education information is a challenging question. With COVID-19 (Coronavirus disease 2019) spreading around the world, this rapid review aims to answer that question and thus to promote evidence-based decision making in health education policy and practice. MethodsWe systematically searched the literature on health education during COVID-19, SARS (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome) epidemics in Medline (via PubMed), Cochrane Library, EMBASE, Web of Science, CBM (China Biology Medicine disc), CNKI (China National Knowledge Infrastructure), and Wanfang Data from their inception until March 31, 2020. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool. ResultsOf 1067 papers found, 24 cross-sectional studies with a total of 35,967 participants were included in this review. The general public lacked good knowledge of SARS and MERS at the early stage of epidemics. Some peoples knowledge, attitude and practice (KAP) of COVID-19 had been improved, but the health behaviors of some special groups including children and their parents need to be strengthened. Negative emotions including fear and stigmatization occurred during the outbreaks. Reliable health information was needed to improve public awareness and mental health for infectious diseases. Health information from nonprofit, government and academic websites was more accurate than privately owned commercial websites and media websites. ConclusionsFor educating and cultivating children, parents should obtain information from the official websites of authorities such as the World Health Organization (WHO) and national Centers for Disease Control, or from other sources endorsed by these authorities, rather than from a general search of the internet or social media.

Breastfeeding of Infants Born to Mothers with COVID-19: A Rapid Review

BackgroundExisting recommendations on whether mothers with COVID-19 should continue breastfeeding are still conflicting. We aimed to conduct a rapid review of mother-to-child transmission of COVID-19 during breastfeeding. MethodsWe systematically searched Medline, Embase, Web of Science, Cochrane library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang, and preprint articles up to March 2020. We included studies relevant to transmission through milk and respiratory droplets during breastfeeding of mothers with COVID-19, SARS, MERS and influenza. Two reviewers independently screened studies for eligibility, extracted data, assessed risk of bias and used GRADE to assess certainty of evidence. ResultsA total of 4481 records were identified in our literature search. Six studies (five case reports and one case series) involving 58 mothers (16 mothers with COVID-19, 42 mothers with influenza) and their infants proved eligible. Five case reports showed that the viral nucleic acid tests for all thirteen collected samples of breast milk from mothers with COVID-19 were negative. A case series of 42 influenza infected postpartum mothers taking precautions (hand hygiene and wearing masks) before breastfeeding showed that no neonates were infected with influenza during one-month of follow-up. ConclusionsThe current evidence indicates that SARS-CoV-2 viral nucleic acid has not been detected in breast milk. The benefits of breastfeeding may outweigh the risk of SARS-CoV-2 infection in infants. Mothers with COVID-19 should take appropriate precautions to reduce the risk of transmission via droplets and close contact during breastfeeding.

Efficacy and Safety of Antibiotic Agents in Children with COVID-19: A Rapid Review

BackgroundThe aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. MethodsWe searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. ResultsSix studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [HR] 0.88, 95% CI 0.47, -1.64], P = 0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. ConclusionsThe benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.