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Objectives To evaluate the performance of nasal mid-turbinate self-testing using rapid antigen detection tests (RDT) for persons with suspected coronavirus disease 2019 (COVID-19) in the community. Self-testing for COVID-19 infection with lateral flow assay severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RDT, provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2. Methods Participants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD-RDT) or Roche SARS-CoV-2 antigen detection test (Roche-RDT). Oro-nasopharyngeal swabs were collected from the participants for quantitative RT-PCR (qRT-PCR) testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture dropped below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined. Results A total of 3201 participants were included (BD-RDT n = 1595; Roche-RDT n = 1606). Sensitivity and specificity of self-testing compared with the qRT-PCR results with a Ct-value below the Ct-value cut-off were 78.4% (95% CI 73.2%–83.5%) and 99.4% (95% CI 99.1%–99.7%), respectively. A higher age was independently associated with a false-negative self-testing result with an odds ratio of 1.024 (95% CI 1.003–1.044). Conclusions Self-testing using currently available RDT has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness.

Background Countries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration. Aim The aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing. Methods The EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries. Results The overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards. Conclusion Our EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.

De behandeling van reumatoïde artritis heeft een revolutie ondergaan sinds de introductie van biologicals. Een bekende complicatie van deze middelen is een verhoging van het risico op ernstige infecties, wat in verschillende mate bij de verschillende klassen voorkomt. Doordat TNF-alfaremmers onder andere granuloomvorming tegengaan, vormen ze een belangrijke risicofactor voor de reactivatie van latente tuberculose (tbc). Tocilizumab remt interleukine-6. Abatacept remt de T-celcostimulatie, waardoor een robuuste T-celrespons wordt tegengegaan. Rituximab, een monoclonaal dat CD20-positieve B-cellen depleteert, heeft als belangrijk risico reactivatie van hepatitis B-virus. Ook hepatitis C-virus- en JC-virusreactivatie zijn bij rituximab beschreven. Het risico op overige ernstige infecties lijkt bij alle biologicals ongeveer even hoog. Een bijzondere categorie zijn de Janus-kinase (JAK)-remmers, die zorgen voor een verminderde expressie van pro-inflammatoire genen. Van deze middelen is bekend dat ze waarschijnlijk een sterk verhoogd risico op herpes zoster geven. Onderzoek naar de invloed van deze middelen op het microbioom staat nog in de kinderschoenen: alleen van TNF-alfaremming is onderzocht wat dit doet op de darmkolonisatie.

In response to the worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent antibody tests that flooded the market, a nationwide collaborative approach in the Netherlands was employed. Forty-one Dutch laboratories joined forces and shared their evaluation data to allow for the evaluation of a quantity of serological assays for SARS-CoV-2 that exceeds the capacity of each individual laboratory. As of April 2020, these performance data had been aggregated and shared in regularly updated reports with other laboratories, Dutch government, public health organizations, and the public. This frequently updated overview of assay performance increased the efficiency of our national laboratory response, supporting laboratories in their choice and implementation of assays. Aggregated performance data for 47 immunoassays for SARS-CoV-2 showed that none of the evaluated immunoassays that detect only IgM or IgA met the diagnostic criteria, indicating that they are not suitable for diagnosing acute infections. For the detection of IgG, only the Biozek Corona virus COVID rapid test, Euroimmun SARS-CoV-2 IgG, and Wantai SARS-CoV-2 antibody (Ab) ELISA met predefined performance criteria in hospitalized patients where samples were collected 14 days post-onset of symptoms (DPO), while for patients with mild or asymptomatic infections, only the Wantai SARS-CoV-2 Ab ELISA met the predefined performance criteria if samples were collected 14 days postonset. Here, we describe this unique nationwide collaboration during the onset of the COVID-19 pandemic; the collected data and their results are an example of what can be accomplished when forces are joined during a public health crisis.

IntroductionSelf-testing for COVID-19 infection with lateral flow assay SARS-CoV-2 rapid antigen detection tests (RDT), provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2. The objective of this study is to evaluate the performance of self-testing using RDT without assistance.MethodsParticipants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD RDT) or Roche SARS-CoV-2 antigen detection test (Roche RDT). Oro-nasopharyngeal swabs were collected from the participants for qRT-PCR testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture was dropping below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined.ResultsA total of 3,215 participants were included (BD RDT n=1604; Roche RDT n=1611). Sensitivity and specificity of self-testing compared to the qRT-PCR results with Ct-value below the Ct-value cut-off was 78.0% (95% CI:72.5-82.8) and 99.4% (95%CI: 99.0-99.6) respectively. Determinants independently associated with a false-negative self-testing results were: higher age, low viral load and finding self-testing difficult.DiscussionSelf-testing using currently available RDT’s has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness. The performance of two tests were comparable. This application has the potential for frequent and extensive testing which may be an aid to lift restrictions to society while controlling the spread of SARS-CoV-2.

Summary Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)‐antibodies, PnPS IgA and IgM‐antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA‐PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti‐PnPS IgM and IgA‐assays in patients with suspected primary immunodeficiency in a large teaching hospital in ’s‐Hertogenbosch, the Netherlands. Serotype‐specific‐PnPS IgG assays were performed; subsequently, 23‐valent‐PnPS IgG assays (anti‐PnPS IgG assays), and later anti‐PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre‐ and six of 10 post‐immunization samples from good responders to PnPS serotype‐specific IgG testing had decreased anti‐PnPS IgA and/or IgM titres. Of these, three pre‐ and no post‐immunization samples were from patients previously classified as ‘no PAD’. Determination of anti‐PnPS IgA and IgM in addition to anti‐PnPS IgG did not reduce the need for serotype‐specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post‐immunization samples: anti‐PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63–0.97; anti‐PnPS IgM + IgG AUC 0.80, 95% CI = 0.62–0.98; anti‐PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51–0.91; anti‐PnPS IgG AUC = 0.93, 95% CI = 0.85–1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype‐specific PnPS IgG can still display impaired anti‐PnPS IgM and IgA responses, and that the additional measurement of anti‐PnPS IgA and IgM could not reduce the need for serotype‐specific IgG testing. Future studies are needed to investigate the clinical relevance of potential ‘specific IgA or IgM antibody deficiency’ in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions., Patients classified as having an intact PnPS IgG antibody response, still can display defective anti‐PnPS IgA and IgM responses. Whether ‘specific IgA or IgM antibody deficiency’ is a clinically relevant form of antibody deficiency should be investigated in future studies.

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% - 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on 'test, trace and isolate'. Keywords: SARS-CoV-2, RT-PCR, serology, sensitivity, public health.

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. However, the clinical sensitivity of RT-PCR remains uncertain. In the present study, Bayesian statistical modeling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RTPCR ranged between 79–95%; while increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should therefore be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on the ‘test, trace and isolate’ principle.

Item does not contain fulltext To rapidly assess possible community transmission in Noord-Brabant, the Netherlands, healthcare workers (HCW) with mild respiratory complaints and without epidemiological link (contact with confirmed case or visited areas with active circulation) were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within 2 days, 1,097 HCW in nine hospitals were tested; 45 (4.1%) were positive. Of six hospitals with positive HCW, two accounted for 38 positive HCW. The results informed local and national risk management.

Background The current reference standard to diagnose a SARS-CoV-2 infection is real-time reverse transcriptase polymerase chain reaction (RT-PCR). This test poses substantial challenges for large-scale community testing, especially with respect to the long turnaround times. SARS-CoV-2 antigen tests are an alternative, but typically use a lateral flow assay format rendering them less suitable for analysis of large numbers of samples. Methods We conducted an evaluation of the Diasorin SARS-CoV-2 antigen detection assay (DAA) compared to real-time RT-PCR (Abbott). The study was performed on 248 (74 qRT-PCR positive, 174 qRT-PCR negative) clinical combined oro-nasopharyngeal samples of individuals with COVID-19-like symptoms obtained at a Municipal Health Service test centre. In addition, we evaluated the analytical performance of DAA with a 10-fold dilution series of SARS-CoV-2 containing culture supernatant and compared it with the lateral flow assay SARS-CoV-2 Roche/SD Biosensor Rapid Antigen test (RRA). Results The DAA had an overall specificity of 100% (95%CI 97.9%–100%) and sensitivity of 73% (95%CI 61.3%–82.7%) for the clinical samples. Sensitivity was 86% (CI95% 74.6%–93.3%) for samples with Ct-value below 30. Both the DAA and RRA detected SARS-CoV-2 up to a dilution containing 5.2 × 102 fifty-percent-tissue-culture-infective-dose (TCID50)/ml. Discussion The DAA performed adequately for clinical samples with a Ct-value below 30. Test performance may be further optimised by lowering the relative light unit (RLU) threshold for positivity assuming the in this study used pre-analytical protocol . The test has potential for use as a diagnostic assay for symptomatic community-dwelling individuals early after disease onset in the context of disease control.

Non-polio enteroviruses (NPEV) and parechoviruses (PeV) are widespread pathogens that cause significant morbidity. Surveillance is based on culturing or genotyping of virus strains found in clinical samples. Sero-surveillance, by measuring neutralising antibodies (nAb) through virus neutralisation assays (VNA), could provide additional information as it offers a more comprehensive overview of exposure to circulating types in the general population. In our study we evaluated Intravenous immunoglobulins (IVIG) to generate sero-surveillance data. We performed VNA of nineteen NPEV and PeV with Dutch IVIG batches from two different time points (2010 and 2017) and an IVIG batch from Vietnam (2011). We compared our findings with geno- and sero-surveillance data and evaluated changes over time and between the two countries. Our findings show a good correlation with what is known from geno-surveillance data. The highest nAb titres were found against strains from Enterovirus B, while we did not observe nAb titres against strains belonging to Enterovirus C. In conclusion, we demonstrated that sero-surveillance by means of IVIG can be used to obtain insight into circulation of EV and PeV genotypes. This is of particular interest for public health, to evaluate changes over time and population susceptibility to emerging genotypes.

Background: Congenital cytomegalovirus (cCMV) infections are the most prevalent intrauterine infections worldwide and are the result of maternal primary or non-primary infections. Early maternal primary infections are thought to carry the highest risk of fetal developmental abnormalities as seen by ultrasound; however, non-primary infections may prove equally detrimental. Methods/Results: This case series presents 5 cases with fetal abnormalities detected in the second and third trimester, in which cCMV infection was ruled out due to negative maternal CMV-IgM. Discussion: This series highlights the possible pitfalls in serology interpretation and fetal diagnosis necessary for appropriate parental counseling. Once fetal abnormalities have been confirmed and cCMV is suspected, maternal CMV serostatus and fetal infection should be determined. Maternal CMV serology may be ambiguous; therefore, caution should be exercised when interpreting the results.

A 46-year-old man presented with a 5-year history of fatigue, frequent painful muscular spasms in the extremities, and tingling sensations in the hands and feet. His medical history consisted of attention-deficit/hyperactivity disorder, a cervical Mycobacterium avium lymphadenitis during childhood and lateral ligament reconstruction of both ankles after trauma. The authors thank the patient for sample contribution and technicians of the Laboratory for Medical Microbiology and Immunology for contributions in diagnostics in the current case. The patient in this case report provided written informed consent for publication.

The epidemiology of Guillain–Barre syndrome (GBS) in tropical areas is different compared with developed countries. We investigated the epidemiology of GBS on the Caribbean island of Aruba. Data were collected retrospectively from all 36 patients hospitalized with GBS between 2003 and 2011 in Aruba. We observed a seasonal distribution of GBS cases with a peak in February. The incidence rate (IR) fluctuated heavily between individual years. The overall IR was 3.93/100,000, which is higher than that observed in developed countries. Serological studies indicated a possible relation of GBS cases with dengue virus infections. We also observed a relation between the annual number of dengue cases in Aruba and the number of GBS cases in the same year. We conclude that the epidemiology of GBS in tropical areas can be different from temperate climate regions and that dengue may be a trigger for developing GBS.

Background The coronavirus disease (COVID-19) situation demands a lot from citizens, health care providers, and governmental institutions. Citizens need to cope with guidelines on social interaction, work, home isolation, and symptom recognition. Additionally, health care providers and policy makers have to cope with unprecedented and unpredictable pressure on the health care system they need to manage. By providing citizens with an app, they always have access to the latest information and can assess their own health. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. Objective The aim of this observational study is to assess people’s use of an app to support them with COVID-19 education, self-assessment, and monitoring of their own health for a 7-day period. In addition, we aim to assess the usability of this data for health care providers and policy makers by applying it to an interactive map and combining it with hospital data. The secondary outcomes of the study were user’s satisfaction with the information provided in the app, perceived usefulness of the app, health care providers they contacted, and the follow-up actions from this contact. Methods This observational cohort study was carried out at the nonacademic teaching hospital “Elisabeth Twee Steden” (ETZ) in Tilburg, Netherlands. From April 1, 2020, onwards ETZ offered the COVID-19 education, self-assessment, and symptom tracking diary to their already existing app for patient education and monitoring. Results Between April 1 and April 20, 2020, a total of 6194 people downloaded the app. The self-assessment functionality was used abundantly to check one’s health status. In total, 5104 people responded to the question about severe symptoms, from which 242 indicated to suffer from severe symptoms. A total of 4929 people responded to the question about mild symptoms, from which 3248 indicated to suffer from these. The data was successfully applied to an interactive map, displaying user demographics and health status. Furthermore, the data was linked to clinical data. App users were satisfied with the information in the app and appreciated the symptom diary functionality. In total, 102 users reached out to a health care provider, leading to 91 contacts. Conclusions Our study demonstrated the successful implementation and use of an app with COVID-19 education, self-assessment, and a 7-day symptom diary. Data collected with the app were successfully applied to an interactive map. In addition, we were able to link the data to COVID-19 screening results from the hospital’s microbiology laboratory. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. Trial Registration Netherlands Trial Register NL8501; https://www.trialregister.nl/trial/8501

In natalizumab-treated patients without previous immunosuppressive treatment, the JCV antibody index is used to stratify PML risk. A high index value indicates that the risk to develop PML is significantly elevated, although probably about 99% of patients with this index value will not develop PML. This minireview aimed to provide an overview of the basic virology and immunology relevant to understanding JCV infections in MS patients, with a focus on what is presently known about antibodies to JCV and how they could be of use to predict and diagnose PML.

Background: Acute influenza-associated encephalopathy/encephalitis (IAE) in adults is a rare but well-known complication of influenza virus infection. The diagnosis is difficult to make due to the absence of distinctive clinical symptoms and validated diagnostic criteria. We present an illustrative case and a case review on acute IAE in adults. Methods: We performed a Medline search of the English literature using the terms influenz*, encephal* and adult, and constructed a database of detailed descriptions of patients with influenza virus infection with influenza-like symptoms at the onset of neurological symptoms. Results: A total of 44 patients were included. Confusion and seizures were the most prevalent neurological symptoms, present in 12 (27%) and 10 (23%) patients, respectively. Magnetic resonance imaging (MRI) was performed in 21 patients and anomalies were found in 13 (62%), with lesions located throughout the brain. Influenza virus RNA was detected in cerebrospinal fluid (CSF) in 5 (16%) of 32 patients. Eight (18%) of the forty-four patients died. The benefits of antiviral and immunomodulatory therapy have not been well studied. Discussion: Our results show that many different neurological symptoms can be present in patients with acute onset IAE. Therefore, the diagnosis should be considered in patients with fever and neurological symptoms, especially during the influenza season. Laboratory diagnosis consists of demonstration of influenza virus RNA in brain tissue, CSF or respiratory samples, and demonstration of intrathecal antibody production against influenza virus. The presence of brain lesions in MRI and influenza virus in CSF appear to be of prognostic value.

Formalin fixation is known to inactivate most viruses in a vaccine production context, but nothing is published about virus activity in tissues treated with alternative, non-crosslinking fixatives. We used a model assay based on cell culture to test formalin and PAXgene Tissue fixative for their virus-inactivating abilities. MDCK, A549, and MRC-5 cells were infected with Influenza A virus, Adenovirus, and Cytomegalovirus, respectively. When 75% of the cells showed a cytopathic effect (CPE), the cells were harvested and incubated for 15 min, or 1, 3, 6, or 24 hours, with PBS (positive control), 4% formalin, or PAXgene Tissue Fix. The cells were disrupted and the released virus was used to infect fresh MDCK, A549, and MRC-5 cells cultured on cover slips in 24-well plates. The viral cultures were monitored for CPE and by immunocytochemistry (ICC) to record viral replication and infectivity. Inactivation of Adenovirus by formalin occurred after 3 h, while Influenza A virus as well as Cytomegalovirus were inactivated by formalin after 15 min. All three virus strains were inactivated by PAXgene Tissue fixative after 15 min. We conclude that PAXgene Tissue fixative is at least as effective as formalin in inactivating infectivity of Influenza A virus, Adenovirus, and Cytomegalovirus.

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating brain infection caused by JC polyomavirus (JCV), primarily seen in patients with severely compromised cellular immunity. Clinical presentation varies depending on the affected white matter. PML prognosis is variable and effective treatments are lacking. Case presentation: A 75-year-old Chinese woman with type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis, treated with low-dose methotrexate and prednisolone for 2.5 years, developed a Pleurostomophora richardsiae infection of her left arm. After 6 months of treating this rare black fungus infection with voriconazole, surgery and immunosuppression discontinuation, she presented with progressive afebrile encephalopathy with right-sided hemiparesis. There were no signs of inflammation or metabolic abnormalities. Brain magnetic resonance imaging revealed diffuse frontal white matter lesions and a cerebrospinal fluid PCR confirmed PML due to JC virus. Severe lymphopenia was never present, and at PML diagnosis, CD4 and CD8 T-cell counts were 454 mm-3 and 277 mm-3. CD8 T-cells were able to respond to JCV VP1 peptide stimulation with TNFα secretion. Peripheral B-cell count was only 8 mm-3. Mirtazapine and Maraviroc were started, but unfortunately, she rapidly deteriorated and died 5 weeks after PML diagnosis. Conclusion: Although peripheral lymphocyte counts were never low and CD4 T-cell count was close to normal, the persistent black fungus infection was a hallmark of severely compromised cellular immunity. The unexpected extremely low absolute B-cell count might suggest a protective role for B-cells. The paradoxical, clinical PML onset months after immunosuppressive discontinuation suggests that it was only discovered in the context of an immune reconstitution inflammatory syndrome.

Background Alloimmune-mediated lung syndromes (allo-LSs) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the pathogenesis. Objective We studied the relation between RV DNA/RNA detection in the upper/lower airways before HCT and the occurrence of allo-LSs. Methods We retrospectively analyzed all HCT recipients between 2004 and 2014, in whom real-time PCR for RV was performed in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluid before HCT. The main outcome of interest was the presence of an allo-LS, which was defined as idiopathic pneumonia syndrome or bronchiolitis obliterans syndrome. Other outcomes were overall survival and treatment-related mortality. We used Cox proportional hazard models, logistic regression models, and Fine-Gray competing risk regression for analyses. Results One hundred seventy-nine children (median age, 6.8 years) were included. RVs were found in 61% (41% in BAL fluid/NPAs and 20% in NPAs only). Rhinovirus was the most frequently detected RV (42%). Allo-LSs occurred in 13%. RV positivity in BAL fluid was a predictor for allo-LSs (hazard ratio, 3.8; 95% CI, 1.4-10.7; P = .01), whereas RV positivity in NPAs only was not. No other predictors were found. Grade II to IV acute graft-versus-host disease related to steroid treatment shows a trend toward a protective effect (odds ratio, 0.16; 95% CI, 0.0-1.3; P = .08). Allo-LSs significantly increased treatment-related mortality (52% ± 10% in allo-LSs and 20% ± 4% in non–allo-LSs, P = .007). Conclusions These results show that pre-HCT BAL fluid RV positivity was a predictor for allo-LSs. Screening for RVs before HCT might identify patients at risk for allo-LSs. This could have implications for prevention and treatment and might subsequently influence the outcomes of HCT., Graphical abstract

A persistentStaphylococcus epidermidisinfection in mice around a subcutaneous polyvinylpyrrolidone-grafted silicon elastomer catheter (SEpvp) but not around a conventional silicon elastomer catheter was observed. With SEpvp pericatheter tissue, protracted and exaggerated interleukin-1β (IL-1β) production was found. Apparently, sustained levels of IL-1β are associated with enhanced susceptibility to biomaterial-associatedS. epidermidisinfection.

Endosomes are major sorting stations in the endocytic route that send proteins and lipids to multiple destinations in the cell, including the cell surface, Golgi complex, and lysosomes. They have an intricate architecture of internal membrane structures enclosed by an outer membrane. Recycling proteins remain on the outer membrane, whereas proteins that are destined for degradation in the lysosome are sorted to the interior. Recently, a retrograde pathway was discovered whereby molecules, like MHC class II of the immune system, return from the internal structures to the outer membrane, allowing their further transport to the cell surface for T cell activation. Whether this return involves back fusion of free vesicles with the outer membrane, or occurs via the continuity of the two membrane domains, is an unanswered question. By electron tomography of cryo-immobilized cells we now demonstrate that, in multivesicular endosomes of B-lymphocytes and dendritic cells, the inner membranes are free vesicles. Hence, protein transport from inner to outer membranes cannot occur laterally in the plane of the membrane, but requires fusion between the two membrane domains. This implies the existence of an intracellular machinery that mediates fusion between the exoplasmic leaflets of the membranes involved, which is opposite to regular intracellular fusion between cytoplasmic leaflets. In addition, our 3D reconstructions reveal the presence of clathrin-coated areas at the cytoplasmic face of the outer membrane, known to participate in protein sorting to the endosomal interior. Interestingly, profiles reminiscent of inward budding vesicles were often in close proximity to the coats.

The traditional view holds that peroxisomes are autonomous organelles multiplying by growth and division. More recently, new observations have challenged this concept. Herein, we present evidence supporting the involvement of the endoplasmic reticulum (ER) in peroxisome formation by electron microscopy, immunocytochemistry and three-dimensional image reconstruction of peroxisomes and associated compartments in mouse dendritic cells. We found the peroxisomal membrane protein Pex13p and the ATP-binding cassette transporter protein PMP70 present in specialized subdomains of the ER that were continuous with a peroxisomal reticulum from which mature peroxisomes arose. The matrix proteins catalase and thiolase were only detectable in the reticula and peroxisomes. Our results suggest the existence of a maturation pathway from the ER to peroxisomes and implicate the ER as a major source from which the peroxisomal membrane is derived.

Biomaterial surfaces may be modified to reduce bacterial adhesion. The susceptibility in mice to Staphylococcus epidermidis infection in tissue surrounding the commonly used catheter materials—silicon elastomer (SE), polyamide (PA), and their surface-modified polyvinylpyrrolidone (PVP)‐grafted derivatives, SE-PVP and PA-PVP, respectively—was assessed. Abscesses developed around SE-PVP. Around SE, PA, and PA-PVP catheters, no signs of infection were observed, although mice carrying PA-PVP developed septicemia after 14‐21 days. S. epidermidis was cultured from the tissue surrounding PA-PVP segments. Cells around PAPVP segments containing large numbers of bacteria were identified as macrophages by use of immunohistochemistry and electron microscopy. This persistence of intracellular bacteria was also observed around SE-PVP, SE, and PA catheters, although to a lesser extent. The cytokine profiles around the 4 materials were different. Implanted biomaterial induces an inflammatory response favorable to the persistence of S. epidermidis. Intracellular persistence of bacteria inside macrophages may be a pivotal process in the pathogenesis of biomaterialassociated infection. A serious problem associated with the use of biomaterials is the occurrence of bacterial infections. The majority of biomaterial-associated infections, 40%‐75%, are caused by the relatively nonpathogenic coagulase-negative staphylococci, especially Staphylococcus epidermidis [1, 2]. Elek and Conen [3] in 1957 were the first to report that susceptibility to bacterial infection was significantly enhanced by the presence of foreign body material. This was confirmed in animal studies [4‐7]. The mechanism underlying this enhancement of susceptibility to infection is still incompletely understood. The pathogenesis of biomaterial-associated infections is a complex process with various contributing factors, such as bacterial virulence, physicochemical properties of the biomaterial, and alterations in the host defense. Adhesion of bacteria to the biomaterial is regarded as the initial step [1, 2, 8‐15]. Subsequently, production of extracellular substances by the adherent bacteria (slime, glycocalix) and attachment of host factors (e.g., blood and tissue proteins, platelets) lead to the for

Acute flaccid myelitis; Enterovirus D68; Surveillance Mielitis flàcida aguda; Enterovirus D68; Vigilància Mielitis flácida aguda; Enterovirus D68; Vigilancia We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.