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
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.
Multisystem inflammatory syndrome and COVID-19: a scoping review
Tuta-Quintero E, Martínez-Ayala C, Mantilla-Beltrán G, Rueda-Rodríguez A, Pimentel J
Boletin medico del Hospital Infantil de Mexico. 2022
BACKGROUND Multisystem inflammatory syndrome temporally associated with COVID-19 presents with similar symptomatology and therapeutic approach to Kawasaki disease in the pediatric population. Given the novelty of the disease and the growing scientific literature on the subject, it is relevant to collect and report available scientific information. This review aimed to explore the medical evidence on multisystem inflammatory syndrome temporally associated with COVID-19 in a population under 18 years of age. METHODS We conducted a scoping review using Scopus and PubMed, including observational (cohort, case-control, and cross-sectional) studies and case series. RESULTS Of the total articles reviewed as of April 10, 2021, 45 articles met eligibility criteria: case series (n = 32), retrospective cohort studies (n = 6), prospective cohort studies (n = 4), case-control studies (n = 2), and cross-sectional studies (n = 1). Gastrointestinal and respiratory symptoms and myocardial dysfunction are the most commonly reported. The most relevant paraclinical markers were lymphopenia, thrombocytopenia, and elevated D-dimer levels. CONCLUSIONS The multisystem inflammatory syndrome temporally associated with COVID-19 presents a broad spectrum of signs and symptoms. Aneurysms of the coronary arteries and myocarditis are usually present in the acute phases of the disease. The early diagnosis led by a multidisciplinary group of pediatric intensivists, infectious disease specialists, cardiologists, and rheumatologists allows adequate and effective medical management.
Comparative efficacy of 19 drug therapies for patients with idiopathic thrombocytopenic purpura: a multiple-treatments network meta-analysis
Zhou H, Fan J, He J, Hu S
Annals of hematology. 2022
Immune thrombocytopenia (ITP) is the most common clinical bleeding disorder with a high mortality rate and poor long-term survival quality in severe patients. There is controversy on how to choose the appropriate treatment. We systematically reviewed 19 randomized controlled trials (including 2615 participants) from January 1, 2015, to April 20, 2021. These investigations compared multiple drugs or their combinations in the therapeutic dose range for the treatment of ITP. The primary endpoint was based on the proportion of patients who responded to these therapies. The efficacy of eltrombopag plus rituximab, avatrombopag, dexamethasone plus anti-HP, and dexamethasone plus rhTPO was significantly higher than placebo (OR: 46.66, 29.44, 2.66, 1.86) or dexamethasone alone (OR: 46.22, 29.01, 2.22, 1.40). Placebo, oral immunosuppressants, and dexamethasone plus oseltamivir were less effective than the other ITP therapies tested. Eltrombopag plus rituximab may be the best choice when starting treatment for ITP.
People with idiopathic thrombocytopenia purpura (ITP) enrolled in clinical trials, and identified by systematic review (n= 2,615, 19 RCTs).
Interventions for ITP: romiplostim, eltrombopag, rituximab, prednisolone, IVIG, efgartimod, dexamethasone or avatrombopag.
Placebo, dexamethasone, danazol or other drug interventions.
The efficacy of eltrombopag plus rituximab, avatrombopag, dexamethasone plus anti-HP, and dexamethasone plus rhTPO was significantly higher than placebo (odds ratio [OR]: 46.66, 29.44, 2.66, 1.86) or dexamethasone alone (OR: 46.22, 29.01, 2.22, 1.40). Placebo, oral immunosuppressants, and dexamethasone plus oseltamivir were less effective than the other ITP therapies tested.
COVID-19 associated with immune thrombocytopenia: a systematic review and meta-analysis
Expert review of hematology. 2022
BACKGROUND Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19 associated complication. This study analyzes the published literature of case reports and case series regarding COVID-19 infection associated with ITP. METHODOLOGY In this systematic review and meta-analysis, a systematic search was conducted through PubMed, Web of Science and Medline through Clarivate, and EBSCO to include the eligible studies. The authors utilized Review Manager 5.4 to conduct quantitative data synthesis for the condition of interest analysis. RESULTS A total of 13 eligible case reports and case series with 42 patients were included in this study; 54.8% of them were males. The pooled mean age of all participants was (59.5 ± 19) years and a median age of 63 years. The estimated mean time from diagnosis with COVID-19 to ITP development was (18.1 ± 21) and the mean time to recovery from ITP was (5.8 ± 4.8) days. The pooled random effect of mean platelet count in the included six studies was (14.52, CI [8.79, 20.25]). CONCLUSION our analysis show that ITP secondary to COVID-19 infection is slightly more prevalent among males (54.8%). Elderly patients were more vulnerable to have the disease as most of the cases were older than 50 years with a median age of 63 years. Most cases developed ITP within 2-3 weeks after COVID-19 infection and recovered in less than one week from ITP.
COVID-19: Main findings after a year and half of unease and the proper scientific progress (Review)
Leretter MT, Vulcanescu DD, Horhat FG, Matichescu A, Rivis M, Rusu LC, Roi A, Racea R, Badea I, Dehelean CA, et al
Experimental and therapeutic medicine. 2022;23(6):424
Free full text
Since the emergence of the disease in late December 2019, numerous studies have been published to date regarding clinical, laboratory and treatment aspects associated with COVID-19. The present study attempts to compare and unify the clinical, para-clinical and therapeutic aspects that have come to light regarding coronavirus disease-19 (COVID 19), mainly in adults. Between April 2020 and September 2021, a comprehensive systematic literature review was performed, which we added to from our own medical experiences. The search was performed on the PubMed, Scopus and Google Scholar databases, comprising studies with analyzable data that were identified alongside studies and documents containing general scientific data. All published studies were written in English, and were from different countries. A 95% confidence interval (CI95) was also calculated for almost each study using the Wilson formula. When compared with preliminary reports between December 2019 and January 2020, the most frequent symptoms were still identified as being fever (68.6%; CI95: 67.5-69.7) and cough (72.7%; CI95: 71.7-73.8). Nevertheless, asymptomatic cases also increased (by 21.4%; CI95: 16.6-27.1). Severe and critical cases accounted for 10.4% (CI95: 9.6-11.1) of all cases. The mean fatality rate was found to be 4% (CI95: 3.6-4.5). The primary co-morbidity found was hypertension (28.9%; CI95: 27-30.8), followed by other underlying cardiovascular diseases (15.4%; CI95: 13.9-16.9) and diabetes (14.5%; CI95: 13.1-16.1). The majority of studies showed lower white blood cell numbers with neutropenia and lymphopenia, and lower platelet levels. The levels of the biomarkers C-reaction protein and erythrocyte sedimentation rate were positive in all studied cases alongside other lab tests, such as examining the D-dimer levels and those of other hepatic, cardiac and renal injury markers. The procalcitonin level was also found to be elevated in many cases, resulting in high usage of antibiotics (83.7%; CI95: 81.2-85.9). Approximately 31.6% (CI95: 29.1-34.1) of the patients required non-invasive ventilation, whereas 9.9% (CI95: 8.1-12.1) of the patients were intubated or placed on extracorporeal membrane oxygenation. The most used antivirals were ribavirin (67.3%; CI95: 63.4-70.9), oseltamivir (52.5%; CI95: 49.4-55.5) and Arbidol™ (34.5%; CI95: 32-37.1). General admittance to the intensive care unit was ~7.2% (CI95: 6.5-7.9) of patients.
Prognostic Accuracy of Cardiovascular Disease Biomarkers in Patients with COVID-19: A Diagnostic Test Accuracy Meta-Analysis
Nasir Kansestani A, Zare ME, Zhang J
The journal of Tehran Heart Center. 2021;16(1):1-14
Background: Several reports have determined that cardiovascular diseases (CVDs) are common complications in patients with coronavirus disease 2019 (COVID-19) and lead them to poor outcomes. CVD biomarkers have, thus, great potential to be used as prognostic biomarkers. We aimed to determine the accuracy of CVD biomarkers for the prognosis of the COVID-19 patient's outcome via a diagnostic test accuracy (DTA) meta-analysis. Methods: Until September 30, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to obtain related papers. The summary points and lines were calculated using bivariate/HSROC model. As outcomes, we considered critical conditions and mortality. Results: A total of 17 659 patients from 33 studies were included. Five biomarkers, namely increased levels of lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase (CK), D-dimer, and thrombocytopenia, met the inclusion criteria. Our results indicated that LDH and cTnI had good accuracy for the prognosis of critical condition (AUC(HSROC)=0.83 and 0.80, respectively), while LDH, cTnI, and D-dimer had acceptable accuracy (AUC(HSROC)=0.74, 0.71, and 0.72, respectively) for the prognosis of mortality. LDH and D-dimer had high sensitivity, whereas cTnI had high specificity. The other biomarkers did not have acceptable accuracy. Significant publication bias was found for D-dimer (P=0.053). Conclusion: Among CVD biomarkers, LDH and cTnI had good accuracy for the prognosis of critical outcomes and acceptable accuracy for the prognosis of mortality, without publication bias. Given their different sensitivities and specificities, we recommend the use of these 2 biomarkers concomitantly.
Immune Thrombocytopenic Purpura in a Patient With SARS-CoV-2 and Epstein-Barr Virus
Galestanian, A., Suthar, K. H., Karnath, B.
A 35-year-old female was admitted to the hospital for menorrhagia and fatigue Initial labs revealed that the patient had severe thrombocytopenia and also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The main objective in this case is to describe the investigation that eventually led to a diagnosis of idiopathic thrombocytopenic purpura (ITP) in the setting of a SARS-CoV-2 coronavirus disease 2019 (COVID-19) infection and co-infection with Epstein-Barr virus (EBV) The majority of ITP cases are idiopathic and most are diagnosed and managed without hospital admission Admission and careful management were warranted in this particular case Interestingly, however, the patient did not have any respiratory complications associated with COVID-19 She was given 1 unit of platelets and subsequently received intravenous corticosteroids Platelet counts improved and the patient was discharged with a course of oral prednisone This case highlights the importance of understanding the differences between primary and secondary ITP
COVID-19 Associated Thrombocytopenia in Children: An Emerging Issue
Hashemieh, M., Tabatabaee, S., Radfar, M., Fahim, P.
International Journal of Pediatrics-Mashhad. 2021;9(6):13635-13642
Thrombocytopenia is a risk factor for increased mortality and morbidity during the Coronavirus Disease 2019 (COVID-19) In patients with COVID-19, the mechanisms lead to thrombocytopenia seems to be multifactorial Thrombotic consumption of platelets in microvasculature, cytokine release, sepsis, and drug induced, direct infection of megakaryocytes and autoimmune destruction of platelets are the leading etiologies in COVID-19 and thrombocytopenia In this overview, the research was conducted by screening the relevant articles evaluating the COVID-19 associated thrombocytopenia in children An electronic search was performed in online databases of Scopus, EMBASE, Cochrane, Web of Science and Medline (via PubMed) with English language from December 2019 up to September 2020 Thrombocytopenia at admission in patients with SARS-CoV-2 infection is common, but delayed phase thrombocytopenia (occurring 2 weeks after beginning of symptoms) is uncertain The delayed phase thrombocytopenia in COVID-19 is more prevalent in infected case with low lymphocyte count at admission and has a significant correlation with higher mortality rate In majority of cases with COVID-19 and thrombocytopenia, the platelet count is mildly decreased Severe thrombocytopenia or a prompt decline in number of platelets often indicates immune mediated thrombocytopenia or in late terminal stages of this infection Thrombocytopenia is a significant finding in patients with severe type of COVID -19 Immune mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients, and can manifest as severe thrombocytopenia It is important for practitioners to be vigilant and aware of this hematologic abnormality
Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis
Palaiodimou L, Stefanou MI, Katsanos AH, Aguiar de Sousa D, Coutinho JM, Lagiou P, Michopoulos I, Naska A, Giannopoulos S, Vadikolias K, et al
BACKGROUND AND OBJECTIVES There is accumulating evidence supporting an association between the "thrombosis and thrombocytopenia syndrome" (TTS) and adenovirus vector-based vaccines against SARS-CoV-2. Yet, TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS We performed a systematic review and meta-analysis of clinical trials, cohorts, case series and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with post-vaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were further included in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95%CI:36-66%; I(2)=61%). TTS was independently associated with a higher likelihood of CVST, when compared to non-TTS patients with thrombotic events after vaccination (OR:13.8; 95%CI:2.0-97.3; I(2)=78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95%CI:21-36%) and 38% (95%CI:27-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval:10 days; 95%CI:8-12) and affected predominantly women (69%, 95%CI:60-77%), under the age of 45, even in the absence of pro-thrombotic risk factors. DISCUSSION Approximately one half of TTS cases present with CVST, while almost one third of TTS patients do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION The pre-specified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).
Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?
Madala, S., Krzyzak, M., Dehghani, S.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral respiratory illness initially described in Wuhan, China, and was declared a pandemic by World Health Organization (WHO) in 2020, and the disease is named coronavirus disease (COVID-19) SARS-CoV2 is known to cause fever, cough, fatigue, and acute respiratory distress syndrome As more patients become infected, extrapulmonary manifestations came to rise and hypercoagulability is one among those COVID-19 could predispose patients to both venous and arterial thromboembolic events which are commonly treated with unfractionated heparin or low molecular weight heparin (LMWH) The treatment of patients who develop heparin-induced thrombocytopenia (HIT) while being treated with heparin or LMWH for COVID-induced thromboembolic complications is challenging We describe a patient admitted to the hospital with COVID-19 pneumonia, found to have a cerebrovascular event treated with unfractionated heparin She also received therapeutic LMWH for anticoagulation on day 1 of presentation due to atrial fibrillation She was diagnosed with HIT and was found to have a pulmonary embolism, aortic arch mural thrombus, and arterial thrombi in the lower extremities As more recent studies showed HIT antibodies in COVID-19 patients who are naive for heparin-based products, COVID-19 may be an independent risk factor for the development of HIT The role of COVID-19 in the development of HIT is uncertain High vigilance is required to diagnose and initiate treatment for HIT early in the disease course as it can be life-threatening