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Revista Pediatric research
Año 2022
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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.Fig. 1FLOWCHART OF THE STUDY SELECTION PROCESS FOR INDIVIDUAL PATIENT DATA EXTRACTION.: Study selection was done in accordance with the PRISMA IPD guidelines.Fig. 2TRENDS FOR PEDIATRIC COVID-19 PATIENTS BY AGE.: Heat map representing the proportion of patients with each presenting symptom (a), clinical sign (b), or abnormal lab values (c) compared to all patients of that age who had information available. Color code ranges from white (0%) to dark gray (100%). The diagonal line indicates that no patients of that age had information available.

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Revista Cardiovascular revascularization medicine : including molecular interventions
Año 2022
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Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.

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Revista Advances in Dermatology and Allergology
Año 2022
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Revista Dermatologic therapy
Año 2021
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Dysgeusia is the first recognized oral symptom of novel coronavirus disease (COVID-19). In this review article, we described oral lesions of COVID-19 patients. We searched PubMed library and Google Scholar for published literature since December 2019 until September 2020. Finally, we selected 35 articles including case reports, case series and letters to editor. Oral manifestations included ulcer, erosion, bulla, vesicle, pustule, fissured or depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, hemorrhagic crust, necrosis, petechiae, swelling, erythema, and spontaneous bleeding. The most common sites of involvement in descending order were tongue (38%), labial mucosa (26%) and palate (22%). Suggested diagnoses of the lesions were aphthous stomatitis, herpetiform lesions, candidiasis, vasculitis, Kawasaki-like, EM-like, mucositis, drug eruption, necrotizing periodontal disease, angina bullosa- like, angular cheilitis, atypical Sweet syndrome, and Melkerson-Rosenthal syndrome. Oral lesions were symptomatic in 68% of the cases. Oral lesions were nearly equal in both genders (49% female, 51% male). Patients with older age and higher severity of COVID-19 disease had more widespread and sever oral lesions. Lack of oral hygiene, opportunistic infections, stress, immunosuppression, vasculitis and hyper-inflammatory response secondary to COVID-19 are the most important predisposing factors for onset of oral lesions in COVID-19 patients. This article is protected by copyright. All rights reserved.

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Revista Journal of thoracic imaging
Año 2021
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OBJECTIVE: Cardiac magnetic resonance imaging (CMR) with its new quantitative mapping techniques has proved to be an essential diagnostic tool for detecting myocardial injury associated with coronavirus disease 2019 (COVID-19) infection. This systematic review sought to assess the important imaging features on CMR in patients diagnosed with COVID-19. MATERIALS AND METHODS: We performed a systematic literature review within the PubMed, Embase, Google Scholar, and WHO databases for articles describing the CMR findings in COVID-19 patients. RESULTS: A total of 34 studies comprising 199 patients were included in the final qualitative synthesis. Of the CMRs 21% were normal. Myocarditis (40.2%) was the most prevalent diagnosis. T1 (109/150; 73%) and T2 (91/144; 63%) mapping abnormalities, edema on T2/STIR (46/90; 51%), and late gadolinium enhancement (LGE) (85/199; 43%) were the most common imaging findings. Perfusion deficits (18/21; 85%) and extracellular volume mapping abnormalities (21/40; 52%), pericardial effusion (43/175; 24%), and pericardial LGE (22/100; 22%) were also seen. LGE was most commonly seen in the subepicardial location (81%) and in the basal-mid part of the left ventricle in inferior segments. In most of the patients, ventricular functions were normal. Kawasaki-like involvement with myocardial edema without necrosis/LGE (4/6; 67%) was seen in children. CONCLUSION: CMR is useful in assessing the prevalence, mechanism, and extent of myocardial injury in COVID-19 patients. Myocarditis is the most common imaging diagnosis, with the common imaging findings being mapping abnormalities and myocardial edema on T2, followed by LGE. As cardiovascular involvement is associated with poor prognosis, its detection warrants prompt attention and appropriate treatment.

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Pre-print ResearchSquare
Año 2021
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Background  We aimed to use individual   patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital. Methods  We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with 30 CYP with SARS-CoV-2 or 5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI). Findings  81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).  Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); ≥3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); ≥3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. Interpretation  Hospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions.

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Revista International journal of clinical practice
Año 2021
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OBJECTIVE: Analyze current literature and reported cases of MISC, concerning its clinical spectrum, complications associated, therapeutic strategies and distinguishing features of other clinical syndromes. METHODS: Extensive literature research was performed in MEDLINE (trough PubMed), Scopus and Web of Science from December 2019 to December 2020. First analysis included all article titles and abstracts screening to identify relevant studies and second analysis included a full text screening of previous selected studies. Eligibility was assessed independently by two authors and disagreements were resolved by discussion and consensus. Data were extracted on MISC definition, demographic data, clinical features, diagnostic tests, laboratory analysis and imaging, therapeutical approach and outcomes. RESULTS: Common symptoms included: gastrointestinal (70%), rash (57%) and cardiovascular (52% with shock). Notable differences with Kawasaki Disease were identified including age, clinical presentation and cardiac involvement. 30% presented positive SARS-CoV-2 2 reverse transcription polymerase chain reaction and 51% positive serologies. 62% received intravenous immunoglobulin and 42% glucocorticoids. 62% required intensive care, 21 children died (<2%). Severe presentations were associated with neurological symptoms, hepatitis and acute kidney injury. CONCLUSIONS: MISC raises concern on its severe cardiac involvement at presentation, with frequent intensive care and immunomodulatory therapy need. Short term outcomes seem to be favorable, with cardiac disfunction recovery and low mortality rates.

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Revista World journal of pediatrics : WJP
Año 2021
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BACKGROUND: We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflammatory syndrome in pediatrics diagnosed during the COVID-19 pandemic. DATA SOURCES: A literature search in Web of Science, PubMed, Scopus, and Science Direct was made up to June 29, 2020. RESULTS: Analysis of 15 articles (318 COVID-19 patients) revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics, Kawasaki-like features as fever (82.4%), polymorphous maculopapular exanthema (63.7%), oral mucosal changes (58.1%), conjunctival injections (56.0%), edematous extremities (40.7%), and cervical lymphadenopathy (28.5%), atypical gastrointestinal (79.4%) and neurocognitive symptoms (31.8%) were also common. They had elevated serum lactic acid dehydrogenase, D-dimer, C-reactive protein, procalcitonin, interleukin-6, troponin I levels, and lymphopenia. Nearly 77.0% developed hypotension, and 68.1% went into shock, while 41.1% had acute kidney injury. Intensive care was needed in 73.7% of cases; 13.2% were intubated, and 37.9% required mechanical ventilation. Intravenous immunoglobulins and steroids were given in 87.7% and 56.9% of the patients, respectively, and anticoagulants were utilized in 67.0%. Pediatric patients were discharged after a hospital stay of 6.77 days on average (95% CI 4.93-8.6). CONCLUSIONS: Recognizing the typical and atypical presentation of the multisystem inflammatory syndrome in pediatric COVID-19 patients has important implications in identifying children at risk. Monitoring cardiac and renal decompensation and early interventions in patients with multisystem inflammatory syndrome is critical to prevent further morbidity.

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BackgroundWe aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital. MethodsWe searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with [&ge;]30 CYP with SARS-CoV-2 or [&ge;]5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI). Findings81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)). Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); [&ge;]3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); [&ge;]3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. InterpretationHospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FundingRH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. Putting Research Into ContextO_ST_ABSEvidence before this studyC_ST_ABSThe risk factors for severe disease following SARS-CoV-2 infection in adults has been extensively studied and reported, with good evidence that increasing age, non-white ethnicity, male gender and co-morbidities increase the risk. SARS-CoV-2 infection in children and young people (CYP) infrequently results in hospital admission and very rarely causes severe disease and death, making it difficult to discern the impact of a range of potential risk factors for severe disease in the many small to moderate sized published studies. More recent larger publications have aimed to address this question in specific populations but the global experience has not been described. We searched Pubmed, European PMC, Medline and Embase from the 1st January 2020 to 21st May 2021 for case series and cohort studies that included all CYP admitted to hospital with 30 children with reverse transcriptase-PCR confirmed SARS-CoV-2 or 5 CYP defined as having PIMS-TS or MIS-C. 57 studies met the eligibility criteria for meta-analysis. Added value of this studyTo our knowledge, this is the first meta-analysis to use individual patient data to compare the odds and risk of critical care admission and death in CYP with COVID-19 and PIMS-TS. We find that the odds of severe disease in hospitalised children is increased in those with multiple co-morbidities, cardiac and neurological co-morbidities and those who are obese. However, the additional risk compared to children without co-morbidity is small. Implications of all the available evidenceSevere COVID-19 and PIMS-TS, whilst rare, can occur in CYP. We have identified pre-existing risk factors for severe disease after SARS-CoV-2 and recommend that those with co-orbidities which place them in the highest risk groups are prioritised for vaccination.

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Revista European journal of pediatrics
Año 2021
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An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases.Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.