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1.
Immunomodulatory Therapy for MIS-C
Ouldali, N., Son, M. B. F., McArdle, A. J., Vito, O., Vaugon, E., Belot, A., Leblanc, C., Murray, N. L., Patel, M. M., Levin, M., et al
Pediatrics. 2023;152(1)
Abstract
CONTEXT Studies comparing initial therapy for multisystem inflammatory syndrome in children (MIS-C) provided conflicting results. OBJECTIVE To compare outcomes in MIS-C patients treated with intravenous immunoglobulin (IVIG), glucocorticoids, or the combination thereof. DATA SOURCES Medline, Embase, CENTRAL and WOS, from January 2020 to February 2022. STUDY SELECTION Randomized or observational comparative studies including MIS-C patients <21 years. DATA EXTRACTION Two reviewers independently selected studies and obtained individual participant data. The main outcome was cardiovascular dysfunction (CD), defined as left ventricular ejection fraction < 55% or vasopressor requirement ≥ day 2 of initial therapy, analyzed with a propensity score-matched analysis. RESULTS Of 2635 studies identified, 3 nonrandomized cohorts were included. The meta-analysis included 958 children. IVIG plus glucocorticoids group as compared with IVIG alone had improved CD (odds ratio [OR] 0.62 [0.42-0.91]). Glucocorticoids alone group as compared with IVIG alone did not have improved CD (OR 0.57 [0.31-1.05]). Glucocorticoids alone group as compared with IVIG plus glucocorticoids did not have improved CD (OR 0.67 [0.24-1.86]). Secondary analyses found better outcomes associated with IVIG plus glucocorticoids compared with glucocorticoids alone (fever ≥ day 2, need for secondary therapies) and better outcomes associated with glucocorticoids alone compared with IVIG alone (left ventricular ejection fraction < 55% ≥ day 2). LIMITATIONS Nonrandomized nature of included studies. CONCLUSIONS In a meta-analysis of MIS-C patients, IVIG plus glucocorticoids was associated with improved CD compared with IVIG alone. Glucocorticoids alone was not associated with improved CD compared with IVIG alone or IVIG plus glucocorticoids.
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Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems
Ruvinsky S, Voto C, Roel M, Fustiñana A, Veliz N, Brizuela M, Rodriguez S, Ulloa-Gutierrez R, Bardach A
Frontiers in pediatrics. 2022;10:881765
Abstract
BACKGROUND With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide; however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. METHODS A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. RESULTS Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6-7.4 years); 60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection; 59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9-10) and PICU stay 5.75 (IQR, 5-6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. CONCLUSION Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.
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Thrombotic events in children and adolescent patients with SARS-Cov-2 infection: a systematic review with meta-analysis on incidence and management
Vitaliti G, Giacchi V, Sciacca M, Ruggieri M, Falsaperla R
Expert review of hematology. 2022
Abstract
OBJECTIVES the present paper aimed to study available literature on the hypercoagulability state of pediatric patients affected by COVID-19, and the current management of thrombosis in these patients, considering that no guidelines have been published since now in this age group. METHODS N 244 titles were screened using the selected MESH words, 180 abstracts and 120 full texts were read, 12 articles were included, and four were analysed by meta-analysis. RESULTS Over 1128 COVID-19 positive patients, nearly half of them developed inflammatory sequelae, and 7.35% (40 patients over 544 who developed MIS-C) had thrombotic events. Less than 50% of patients with inflammatory disease were under anticoagulant prophylactic treatment, and doses of anticoagulant protocols vary from different centres. Thrombotic events prevented after the start of unfractioned heparin (UFH) therapy, even if 1.06% (4 patients) died. Only two patients presented complications after anticoagulant treatment, with non-fatal bleeding after UFH treatment. No other complications were reported. No difference in the incidence of thrombotic events between patients under prophylactic low molecular weight heparin (LMWH) and without was found in meta-analysis (p=0.32). CONCLUSIONS Little is known on the incidence and management of hyper coagulopathy in pediatric COVID-19 infection. Further studies have to clarify this topic.
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Characteristics and conflicting recommendations of clinical practice guidelines for COVID-19 management in children: A scoping review
Quincho-Lopez A, Chávez-Rimache L, Montes-Alvis J, Taype-Rondan A, Alvarado-Gamarra G
Travel medicine and infectious disease. 2022;48:102354
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Abstract
BACKGROUND Clinical practice guidelines (CPGs) are statements that should be rigorously developed to guide clinicians' decision-making. However, given the scarce evidence for certain vulnerable groups like children, CPGs' recommendations formulation could be challenging. METHODS We conducted a scoping review of CPGs for COVID-19 management in children. Documents were included if they claimed to be a "clinical practice guideline", published between January and October 2021, and described the process followed to issue their recommendations. We assessed the quality using the "Appraisal of Guidelines for Research and Evaluation II" (AGREE-II) and described how the recommendations were reached. RESULTS We found five CPGs that fulfilled our inclusion criteria. The median score on the overall AGREE-II evaluation was 61% (range: 49%-72%), and the score on the third domain referred to the rigor of methodological development was 52% (range: 25%-88%). Recommendations for remdesivir, tocilizumab, and intravenous immunoglobulin were heterogeneous across CPGs (in favor, against, no recommendation), as well as the methodologies used to present the evidence, perform the benefits/harms balance, and issue the recommendation. CONCLUSIONS Heterogeneous recommendations and justifications across CPGs were found in the three assessed topics. Future CPGs should describe in detail their evidence-to-decision process to issue reliable and transparent recommendations.
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Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review
Shaiba LA, More K, Hadid A, Almaghrabi R, Al Marri M, Alnamnakani M, Shah P
Neonatology. 2022;:1-13
Abstract
INTRODUCTION Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. METHODS We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. RESULTS Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. CONCLUSION The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.
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IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis
Rauniyar R, Mishra A, Kharel S, Giri S, Rauniyar R, Yadav S, Chaudhary G
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale. 2022;2022:9458653
Abstract
BACKGROUND There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. METHODS PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I (2) > 50% and fixed-effects model was used if I (2) < 50%. RESULTS We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I (2) 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I (2) 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I (2) 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I (2) 75.40%). CONCLUSION This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.
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Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
Abstract
The 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. We 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. A total of nine 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, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) 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, most of the 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.Conclusions: Overall, 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. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
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From H1N1 to COVID-19: What we have seen in children with hemoglobinopathies
Oliveira CM, Soares VJ, Rechenmacher C, Daudt LE, Michalowski MB
Clinics (Sao Paulo, Brazil). 2022;77:100004
Abstract
This work aimed to better understand the impact of pandemics of respiratory viruses on children with hemoglobinopathies through a comprehensive review of the literature. MEDLINE, SCIELO, LILACS, and PUBMED were used as data sources to find articles without time period restrictions. Previous observations suggest that patients with hemoglobinopathies are a group especially susceptible to the complications of viral respiratory infections, with greater morbidity and mortality related to them. Within this context, this review found that, during the 2009 H1N1 pandemic, the risk of hospitalization in children and adults increased, especially in patients with a history of complications such as acute chest syndrome. In addition, the Coronavirus Disease 2019 (COVID-19) pandemic appears to have less repercussion among children with hemoglobinopathies compared to adults, similar to what is seen in the general population. In the H1N1 pandemic, patients with hemoglobinopathies behaved as a group more susceptible to complications, with increased morbidity and mortality. However, for COVID-19, the existing data to date on these patients do not show the same clinical impact. Thus, although these children deserve attention in case of infection due to their potential risks, they seem to have a favorable evolution.
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Coronavirus disease 2019 (COVID-19) and priapism: An unexplored association
Malinga DM, Laher AE, McDowall J, Adam A
Current urology. 2022;16(2):55-62
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has an established impact on multiple organ systems, including the vascular and urogenital systems. Vascular effects may include venous thromboembolic disease, which could theoretically be a precursor to priapism-a urological emergency defined as an abnormal condition of prolonged penile erection lasting >4 hours. To better explore this association, we critically appraised all the published COVID-19 cases associated with priapism. MATERIALS AND METHODS After PROSPERO registration (CRD42021245257), a systematic search of Google Scholar, Scopus, Embase, Web of Science, PubMed, Cumulative Index to Nursing and Allied Health Literature, Global Index Medicus, and Cochrane Database of Systematic Reviews was performed using specific search terms. The following study metadata were extracted: age, requirement for respiratory support, cavernous blood gas findings, management of priapism, and patient outcomes. RESULTS Fifteen single-patient case reports were included in this review. Of these, all of the patients presented with ischemic priapism, 9 patients (60.0%) were >60 years of age, 4 (26.7%) reported more than a single episode of priapism, 11 (73.3%) presented with pneumonia, 8 (53.3%) required mechanical ventilation, D-dimer was elevated in 5 of the 6 (83.3%) patients in whom this was reported, and among the 13 patients in whom mortality was reported, 4 (30.8%) died. CONCLUSIONS Early reports suggest a prognostic relationship between COVID-19 and coexisting priapism. However, owing to commonalities in their pathophysiology and the small dataset reported in the literature, the probable association between COVID-19 and priapism is still theoretical. Further research is needed to confirm this association.
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Trends in clinical presentation of children with COVID-19: a systematic review of individual participant data
Christophers B, Gallo Marin B, Oliva R, Powell WT, Savage TJ, Michelow IC
Pediatric research. 2022;91(3):494-501
Abstract
BACKGROUND There are sparse patient-level data available for children with novel coronavirus disease (COVID-19). Therefore, there is an urgent need for an updated systematic literature review that analyzes individual children rather than aggregated data in broad age groups. METHODS Six databases (MEDLINE, Scopus, Web of Science, CINAHL, Google Scholar, medRxiv) were searched for studies indexed from January 1 to May 15, 2020, with MeSH terms: children, pediatrics, COVID-19, SARS-CoV-2. 1241 records were identified, of which only unique papers in English with individual patient information and documented COVID-19 testing were included. This review of 22 eligible studies followed Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. RESULTS A total of 123 patients from five countries were identified. 46% were females. The median age was 5 years (IQR = 8). At presentation, 62% had a fever, 32% had a cough, 58% had a single symptom, and 21% were asymptomatic. Abnormal chest imaging was seen in 62% (65/105) of imaged and 76.9% (20/26) of asymptomatic children. A minority of children had elevated platelets, CRP, lactate dehydrogenase, and D-dimer. CONCLUSION Data from this independent participant data systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. IMPACT This systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. By using an independent participant data approach, this analysis underscores the challenge of diagnosing COVID-19 in pediatric patients due to the wide variety of symptoms and seemingly poor correlation of imaging findings with symptomatic disease. The data presented from individual patients from case series or cohort studies add more granularity to the current description of pediatric COVID-19.
