Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID

Background Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with SARS-CoV-2. The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID. Methods We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/sex/infection/vaccine-matched patients with long COVID. Findings Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785. Conclusions These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.info:eu-repo/semantics/publishedVersio

A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation. Spread is mainly through close contact during sexual activities. Few cases are reported among women and children. Targeted interventions of at-risk groups are needed to stop further transmission. © 2022 European Centre for Disease Prevention and Control (ECDC). All rights reserved.The authors affiliated with the World Health Organization (WHO) are alone responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO. The co-author is a fellow of the ECDC Fellowship Programme, supported financially by the European Centre for Disease Prevention and Control (ECDC). The views and opinions expressed herein do not state or reflect those of ECDC. ECDC is not responsible for the data and information collation and analysis and cannot be held liable for conclusions or opinions drawn

The relationship between dramatic play and creativity in young children

SIGLEAvailable from British Library Document Supply Centre- DSC:DX178317 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Treatment of anemia in low risk myelodysplastic syndromes with granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 mu g/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a >50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined

A severe gastroenteritis outbreak of Salmonella enterica serovar Enteritidis PT8, with PFGE profile XbaI.0024 and MLVA profile 2-9-7-3-2 following a christening reception, Greece, 2016

In June 2016, a Salmonella enterica serovar Enteritidis outbreak (n = 56) occurred after a christening reception in Central Greece, mainly affecting previously healthy adults; one related death caused media attention. Patients suffered from profuse diarrhoea, fever and frequent vomiting episodes requiring prolonged hospitalisation and sick leave from work, with a 54% hospital admission rate. The majority of cases experienced serious illness within <12 h of attending the party. We investigated the outbreak to identify the source(s) of infection and contributing factors to the disease severity. From the retrospective cohort study, the cheesy penne pasta was the most likely vehicle of infection (relative risk 7.8; 95% confidence interval 3.6-16.8), explaining 79% of the cases. S. enterica ser. Enteritidis isolates were typed as phage-type PT8, pulsed-field gel electrophoresis type XbaI.0024, multiple locus variable-number tandem repeat analysis-type 2-9-7-3-2. The strain did not share the single-nucleotide polymorphism address of the concurrent European S. enterica ser. Enteritidis PT8 outbreak clusters. Following five consecutive years with no documented S. enterica ser. Enteritidis outbreaks in Greece, this outbreak, likely associated with a virulent strain, prompted actions towards the enhancement of the national Salmonella molecular surveillance and control programmes including the intensification of training of food handlers for preventing similar outbreaks in the future. Advanced molecular techniques were useful in distinguishing unrelated outbreak strains. Copyright © 2017 Cambridge University Press