Abstract

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.

Abstract

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.

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized COVID-19 patients develop immunoglobulin Gs (IgGs) that recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia and thrombosis (HIT), however, independent of heparin exposure. These antibodies activate platelets in the presence of TLR9 stimuli, stimuli that are prominent in COVID-19. Strikingly, 4 out of 42 antibodies cloned from IgG1 (+) RBD-binding B cells could activate platelets. These antibodies possessed, in the heavy-chain complementarity-determining region 3, an RKH or Y (5) motif that we recently described among platelet-activating antibodies cloned from HIT patients. RKH and Y (5) motifs were prevalent among published RBD-specific antibodies, and 3 out of 6 such antibodies tested could activate platelets. Features of platelet activation by these antibodies resemble those by pathogenic HIT antibodies. B cells with an RKH or Y (5) motif were robustly expanded in COVID-19 patients. Our study demonstrates that SARS-CoV-2 infection drives the development of a subset of RBD-specific antibodies that can activate platelets and have activation properties and structural features similar to those of the pathogenic HIT antibodies.

Abstract

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).

Abstract

Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear.Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models.Results: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 x 10(9)/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization.Conclusions: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.