The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either ...population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.
Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, ...SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.
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•11/464 (2.4%) patients presenting with non-traumatic neurological injury had evidence of current/recent HEV infection.•In 7/11 cases HEV RNA was found in the serum.•Three cases were ...neuralgic amyotrophy with bilateral symptoms, which is the HEV-associated phenotype.•The relationship between HEV and neuralgic amyotrophy is causal.•The relationship between HEV and other neurological syndromes requires further study.
Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury.
Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands.
Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8–145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus.
In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted.
Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.
Miscarriage Associated with Zika Virus Infection van der Eijk, Annemiek A; van Genderen, Perry J; Verdijk, Rob M ...
New England journal of medicine/The New England journal of medicine,
2016-Sep-08, Letnik:
375, Številka:
10
Journal Article
Abstract Hepatitis E virus (HEV) infections are not limited to the liver but may also affect other organs. Several diseases, including Guillain-Barré syndrome, neuralgic amyotrophy, ...glomerulonephritis, cryoglobulinemia, pancreatitis, lymphoma, thrombopenia, meningitis, thyreoiditis and myocarditis have been observed in the context of hepatitis E. To date the definite pathophysiological links between HEV and extrahepatic manifestations are not yet established. However, it is suggested that HEV-infection might be causative based on serological studies, case series, in vitro data and animal models. In particular neuronal and renal diseases as well as pancreatitis seem to be caused by HEV, while a causative relationship between HEV and other diseases is more doubtful. Either direct cytopathic tissue damage by extrahepatic replication or immunological processes induced by an overwhelming host immune response are possible origins of HEV-associated extrahepatic manifestations. Hepatologists should be aware of the possibility of acute or chronically HEV-infected patients to develop extrahepatic manifestations while neurologists, nephrologists, rheumatologists and other groups of physicians should consider HEV-infection as a potential differential diagnosis when observing one of the hereby described diseases. Ribavirin and steroids have been used in small groups of patients with extrahepatic manifestations, but the efficacy of these drugs still needs to be verified by large, multicenter studies. This article comprehensively reviews the published literature regarding HEV and extrahepatic manifestations and discusses the probability of specific extrahepatic diseases to be caused by previous or ongoing HEV-infection and summarizes the published knowledge about antiviral treatment in extrahepatic disorders.
Background: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse ...histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. Methods: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. Results: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0.007) but not with the severity of maternal COVID-19 disease. Conclusion: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease.
The aim of this study was to define the therapeutic range for ribavirin (RBV) in transplant recipients with chronic hepatitis E virus (HEV) infection. In this retrospective multicentre cohort study, ...data of adult transplant recipients with chronic HEV infection, who had been treated with RBV monotherapy between 01‐3‐2008 and 01‐08‐2018, were included. ROC curve analyses were performed, and the half‐maximal effective RBV concentration was calculated to determine a representative therapeutic range. In 96 patients, RBV monotherapy for a median of three months resulted in a sustained virologic response in 63.5% of the patients, while 88.5% of the patients developed anaemia. RBV plasma concentrations at steady state were significantly higher in clinical responders compared with clinical non‐responders: median 1.96 (IQR 1.81‐2.70) versus 0.49 (IQR 0.45‐0.73) mg/L, P = .0004. RBV caused a dose‐dependent haemoglobin reduction with higher RBV plasma concentrations resulting in more haemoglobin reduction. The therapeutic range for RBV for chronic HEV infection in transplant recipients ranges between 1.8 and 2.3 mg/L.
The aim of the study was to determine whether Guillain-Barré syndrome (GBS) is associated with preceding hepatitis E virus infection.
The frequency of hepatitis E virus (HEV) infections was ...determined by anti-HEV serology in a cohort of 201 patients with GBS and 201 healthy controls with a similar distribution in age, sex, and year of sampling. Blood samples from patients with GBS were obtained in the acute phase before treatment. In a subgroup of patients with GBS, blood, stool, and CSF samples were tested for HEV RNA.
An increased ratio of anti-HEV immunoglobulin (Ig) M antibodies was found in 10 patients with GBS (5.0%) compared with 1 healthy control (0.5%, odds ratio 10.5, 95% confidence interval 1.3-82.6, p = 0.026). HEV RNA was detected in blood from 3 of these patients and additionally in feces from 1 patient. Seventy percent of anti-HEV IgM-positive patients had mildly increased liver function tests. All CSF samples tested negative for HEV RNA. The presence of anti-HEV IgM in patients with GBS was not related to age, sex, disease severity, or clinical outcome after 6 months.
In the Netherlands, 5% of patients with GBS have an associated acute HEV infection. Further research is required to determine whether HEV infections also precede GBS in other geographical areas.
•3D-based primary intestinal organoids support the infection of both experimental and patient-derived rotavirus strains.•Rotavirus infection provokes the induction of interferon-stimulated genes in ...organoids.•Interferon-alpha and ribavirin inhibit rotavirus replication in organoids.•Organoids infected with patient rotavirus can be potentially utilized for personalized evaluation of antivirals.
Despite the introduction of oral vaccines, rotavirus still kills over 450,000 children under five years of age annually. The absence of specific treatment prompts research aiming at further understanding of pathogenesis and the development of effective antiviral therapy, which in turn requires advanced experimental models. Given the intrinsic limitations of the classical rotavirus models using immortalized cell lines infected with laboratory-adapted strains in two dimensional cultures, our study aimed to model infection and antiviral therapy of both experimental and patient-derived rotavirus strains using three dimensional cultures of primary intestinal organoids. Intestinal epithelial organoids were successfully cultured from mouse or human gut tissues. These organoids recapitulate essential features of the in vivo tissue architecture, and are susceptible to rotavirus. Human organoids are more permissive to rotavirus infection, displaying an over 10,000-fold increase in genomic RNA following 24h of viral replication. Furthermore, infected organoids are capable of producing infectious rotavirus particles. Treatment of interferon-alpha or ribavirin inhibited viral replication in organoids of both species. Importantly, human organoids efficiently support the infection of patient-derived rotavirus strains and can be potentially harnessed for personalized evaluation of the efficacy of antiviral medications. Therefore, organoids provide a robust model system for studying rotavirus–host interactions and assessing antiviral medications.
Background
Solid organ transplant recipients are at high risk to develop (complicated) herpes zoster (HZ). Booster vaccination could prevent HZ. However, end-stage renal disease (ESRD) patients show ...poor immunological responses to vaccinations. We studied the effect of a live attenuated VZV booster vaccine on VZV-specific B and T cell memory responses in ESRD patients and healthy controls. NL28557.000.09,
www.toetsingonline.nl
Methods
VZV-seropositive patients, aged ≥50 years, awaiting kidney transplantation, were vaccinated with Zostavax
®
. Gender and age-matched VZV-seropositive potential living kidney donors were included as controls. VZV-specific IgG titers were measured before, at 1, 3 and 12 months post-vaccination. VZV-specific B and T cell responses before, at 3 months and 1 year after vaccination were analysed by flow-cytometry and Elispot, respectively. Occurrence of HZ was assessed at 5 years post-vaccination.
Results
26 patients and 27 donors were included. Median VZV-specific IgG titers were significantly higher at all time-points post-vaccination in patients (mo 1: 3104 IU/ml 1967-3825, p<0.0001; mo 3: 2659 1615-3156, p=0.0002; mo 12: 1988 1104-2989, p=0.01 vs. pre: 1397 613-2248) and in donors (mo 1: 2981 2126-3827, p<0.0001; mo 3: 2442 2014-3311, p<0.0001; mo 12: 1788 1368-2460, p=0.0005 vs. pre: 1034 901-1744. The patients’ IgG titers were comparable to the donors’ at all time-points. The ratio VZV-specific B cells of total IgG producing memory B cells had increased 3 months post-vaccination in patients (0.85 0.65-1.34 vs. pre: 0.56 0.35-0.81, p=0.003) and donors (0.85 0.63-1.06 vs. pre: 0.53 0.36-0.79, p<0.0001) and remained stable thereafter in donors. One year post-vaccination, the percentage of CD4+ central memory cells had increased in both patients (0.29 0.08-0.38 vs. 0.12 0.05-0.29, p=0.005) and donors (0.12 0.03-0.37 vs. 0.09 0.01-0.20, p=0.002) and CD4+ effector memory cells had increased in donors (0.07 0.02-0.14 vs. 0.04 0.01-0.12, p=0.007). Only 1 patient experienced HZ, which was non-complicated.
Conclusion
VZV booster vaccination increases VZV-specific IgG titers and percentage VZV-specific memory T-cells for at least 1 year both in ESRD patients and healthy controls. VZV-specific memory B cells significantly increased in patients up to 3 months after vaccination. Prophylactic VZV booster vaccination prior to transplantation could reduce HZ incidence and severity after transplantation.
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