Antigen point-of-care tests (AgPOCTs) can accelerate SARS-CoV-2 testing. As some AgPOCTs have become available, interest is growing in their utility and performance. Here we aimed to compare the ...analytical sensitivity and specificity of seven commercially available AgPOCT devices.
In a single-centre, laboratory evaluation study, we compared AgPOCT products from seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test, the RapiGEN BIOCREDIT COVID-19 Ag, the Healgen Coronavirus Ag Rapid Test Cassette (Swab), the Coris BioConcept COVID-19 Ag Respi-Strip, the R-Biopharm RIDA QUICK SARS-CoV-2 Antigen, the nal von minden NADAL COVID-19 Ag Test, and the Roche-SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant SARS-CoV-2 nucleoprotein, cultured endemic and emerging coronaviruses, stored respiratory samples with known SARS-CoV-2 viral loads, stored samples from patients with respiratory pathogens other than SARS-CoV-2, and self-sampled swabs from healthy volunteers. We estimated analytical sensitivity in terms of approximate viral concentrations (quantified by real-time RT-PCR) that yielded positive AgPOCT results, and specificity in terms of propensity to generate false-positive results.
In 138 clinical samples with quantified SARS-CoV-2 viral load, the 95% limit of detection (concentration at which 95% of test results were positive) in six of seven AgPOCT products ranged between 2·07 × 106 and 2·86 × 107 copies per swab, with an outlier (RapiGEN) at 1·57 × 1010 copies per swab. The assays showed no cross-reactivity towards cell culture or tissue culture supernatants containing any of the four endemic human coronaviruses (HCoV‑229E, HCoV‑NL63, HCoV‑OC43, or HCoV‑HKU1) or MERS-CoV, with the exception of the Healgen assay in one repeat test on HCoV-HKU1 supernatant. SARS-CoV was cross-detected by all assays. Cumulative specificities among stored clinical samples with non-SARS-CoV-2 infections (n=100) and self-samples from healthy volunteers (n=35; cumulative sample n=135) ranged between 98·5% (95% CI 94·2–99·7) and 100·0% (97·2–100·0) in five products, with two outliers at 94·8% (89·2–97·7; R-Biopharm) and 88·9% (82·1–93·4; Healgen). False-positive results did not appear to be associated with any specific respiratory pathogen.
The sensitivity range of most AgPOCTs overlaps with SARS-CoV-2 viral loads typically observed in the first week of symptoms, which marks the infectious period in most patients. The AgPOCTs with limit of detections that approximate virus concentrations at which patients are infectious might enable shortcuts in decision making in various areas of health care and public health.
EU's Horizon 2020 research and innovation programme, German Ministry of Research, German Federal Ministry for Economic Affairs and Energy, German Ministry of Health, and Bill & Melinda Gates Foundation.
Potential zoonotic sources of SARS‐CoV‐2 infections Jo, Wendy K.; Oliveira‐Filho, Edmilson Ferreira; Rasche, Andrea ...
Transboundary and emerging diseases,
July 2021, Volume:
68, Issue:
4
Journal Article
Peer reviewed
Open access
The severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) causing coronavirus disease‐2019 (COVID‐19) likely has evolutionary origins in other animals than humans based on genetically related ...viruses existing in rhinolophid bats and pangolins. Similar to other animal coronaviruses, SARS‐CoV‐2 contains a functional furin cleavage site in its spike protein, which may broaden the SARS‐CoV‐2 host range and affect pathogenesis. Whether ongoing zoonotic infections are possible in addition to efficient human‐to‐human transmission remains unclear. In contrast, human‐to‐animal transmission can occur based on evidence provided from natural and experimental settings. Carnivores, including domestic cats, ferrets and minks, appear to be particularly susceptible to SARS‐CoV‐2 in contrast to poultry and other animals reared as livestock such as cattle and swine. Epidemiologic evidence supported by genomic sequencing corroborated mink‐to‐human transmission events in farm settings. Airborne transmission of SARS‐CoV‐2 between experimentally infected cats additionally substantiates the possibility of cat‐to‐human transmission. To evaluate the COVID‐19 risk represented by domestic and farmed carnivores, experimental assessments should include surveillance and health assessment of domestic and farmed carnivores, characterization of the immune interplay between SARS‐CoV‐2 and carnivore coronaviruses, determination of the SARS‐CoV‐2 host range beyond carnivores and identification of human risk groups such as veterinarians and farm workers. Strategies to mitigate the risk of zoonotic SARS‐CoV‐2 infections may have to be developed in a One Health framework and non‐pharmaceutical interventions may have to consider free‐roaming animals and the animal farming industry.
Canine circoviruses (CanineCV's), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. ...Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV's. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV's that have resulted in the circulation of newly emerging CanineCV lineages.
Abstract
Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza ...vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10−4 (95% highest posterior density (HPD), 5.4–7.5 × 10−4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10−4 (95% HPD, 5–6.5 × 10−4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10−3 (95% HPD, 2.3–2.7 × 10−3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.
•Morbilliviruses have caused large epizootics in marine mammals in recent decades.•Phylogenetic analysis shows that aquatic and terrestrial mammals are not distinct.•Marine mammals display ...differential susceptibility to morbillivirus infections.•Terrestrial carnivores can facilitate morbillivirus spread to aquatic environments.•Morbilliviruses cross-species infections in marine mammals are poorly characterized.
Transmission of morbilliviruses within and among marine mammal species has been documented in a variety of marine habitats. Cetacean morbillivirus spreads between cetacean species in the aquatic environment whereas both phocine distemper virus and canine distemper virus have been associated with transmission within and between pinniped and terrestrial carnivore species in their natural habitat and at the aquatic–terrestrial interface. Periodically these viruses have caused large epizootics involving thousands of animals, due to sustained intra-species virus transmission. Social behavior of host species, marine habitat, geographical barriers and virus–host adaptations all likely contribute toward modulating virus spread. In combination with increased surveillance and whole genome sequencing, further research into ecological and host factors will be pivotal in better understanding the global transmission dynamics of marine morbilliviruses.
SLC6A1-related disorder is a genetic neurodevelopmental disorder that is caused by loss of function variants in the
gene. Solute Carrier Family 6 Member 1 (
) gene encodes for gamma-aminobutyric acid ...(GABA) transporter type 1 (GAT1), which is responsible for reuptake of GABA from the synaptic cleft. Tight regulation of GABA levels plays an important role in brain development by balancing inhibitory and excitatory neuronal signaling. Consequently, individuals with SLC6A1-related disorder can have manifestations such as developmental delay, epilepsy, autism spectrum disorder, and a subset have developmental regression.
In this study, we identified patterns of developmental regression among a cohort of 24 patients with SLC6A1-related disorder and assessed for clinical characteristics associated with regression. We reviewed medical records of patients with SLC6A1-related disorder and divided subjects into two groups: 1) regression group and 2) control group. We described the patterns of developmental regression including whether there was a trigger prior to the regression, multiple episodes of regression, and whether or not skills were recovered. We assessed the relationship of clinical characteristics among the regression and control groups including demographic factors, seizures, developmental milestone acquisition, gastrointestinal problems, sleep problems, autism spectrum disorder, and behavioral problems.
Individuals with developmental regression had a loss of skills that were previously mastered in developmental domains including speech and language, motor, social, and adaptive skills. The mean age at regression was 2.7 years and most subjects had regression of language or motor skills triggered by seizures, infection, or spontaneously. Although there was no significant difference in clinical characteristics between the two groups, there was a higher prevalence of autism and severe language impairment in the regression group.
Future studies of a larger cohort of patients are required to make definitive conclusions. Developmental regression is often a sign of severe neurodevelopmental disability in genetic syndromes, but it is poorly understood in SLC6A1-related disorder. Understanding the patterns of developmental regression and the associated clinical characteristics in this rare disorder will be important to medical management, prognostication, and could impact the design of future clinical trials.
Comprehensive genomic analysis including exome and genome sequencing is increasingly being utilized in research studies, leading to the generation of incidental genetic findings. It is unclear how ...researchers plan to deal with incidental genetic findings.
We conducted a survey of the practices and attitudes of 234 members of the US genetic research community and performed qualitative semistructured interviews with 28 genomic researchers to understand their views and experiences with incidental genetic research findings.
We found that 12% of the researchers had returned incidental genetic findings, and an additional 28% planned to do so. A large majority of researchers (95%) believe that incidental findings for highly penetrant disorders with immediate medical implications should be offered to research participants. However, there was no consensus on returning incidental results for other conditions varying in penetrance and medical actionability. Researchers raised concerns that the return of incidental findings would impose significant burdens on research and could potentially have deleterious effects on research participants if not performed well. Researchers identified assistance needed to enable effective, accurate return of incidental findings.
The majority of the researchers believe that research participants should have the option to receive at least some incidental genetic research results.
Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public ...health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefore, efforts to eradicate depression should be directed towards understanding the pathomechanisms involved in the hope of finding cost-effective treatment alternatives. The pathophysiology of MDD comprises the breakdown of different pathways, including the hypothalamus-pituitary-adrenal (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission, affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. In addition, evidence from different studies suggests that impairment of glial functions appears to be a major contributor as well. Thus, the intricate role between glia, namely microglia and astrocytes, and the central nervous system's (CNSs) immune response is briefly discussed, highlighting the kynurenine pathway as a pivotal player. Moreover, evaluations of different treatment strategies targeting the inflammatory response are considered. The immuno-modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an attractive and plausible candidate in spite of controversial findings. Further research investigating the role of VDR in mood disorders is warranted.
Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological tests detecting viral antigen or ...virus-specific antibodies.
We provide an overview of the challenges towards serological testing for the most important emerging arboviruses, including Zika, dengue and chikungunya viruses.
We retrieved a data set on performance of commercially available antibody- and antigen-detecting tests from 89 peer-reviewed articles conducting a systematic literature research in PubMed.
We identified commonly used antibody- and antigen-detecting tests and analysed their overall performance. We discuss how timing of serological testing and the use of paired samples from acute and convalescent phases of infection are crucial to optimize diagnostic sensitivity and specificity. We then exemplify how serological diagnostics are challenged by the patient's infection history through the ‘original antigenic sin’ and cross-reactive antibodies in the context of global co-circulation of antigenically related viruses. We highlight how individual infection histories with different arboviruses and with other pathogens such as herpes viruses and Plasmodia can produce inaccurate test results. We show that rapid tests for antibody and antigen detection in point-of-care settings have a significantly lower sensitivity compared with laboratory-based tests such as ELISA. We show that the performance of antibody- and antigen-detecting tests varies greatly between tropical regions of endemic transmission and non-endemic regions. Finally, we highlight that test sensitivity and specificity have to be equilibrated carefully and frequently either of them must be prioritized over the other, depending on disease prevalence and intended use of tests.
For reliable serological diagnostics, it is essential to be aware of inherent test limitations. Although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Summary
Objective
This study evaluated factors influencing reproductive decision‐making in families containing multiple individuals with epilepsy.
Methods
One hundred forty‐nine adults with epilepsy ...and 149 adult biological relatives without epilepsy from families containing multiple affected individuals completed a self‐administered questionnaire. Participants answered questions regarding their belief in a genetic cause of epilepsy (genetic attribution) and estimated risk of epilepsy in offspring of an affected person. Participants rated factors for their influence on their reproductive plans, with responses ranging from “much more likely” to “much less likely” to want to have a child. Those with epilepsy were asked, “Do you think you would have wanted more (or any) children if you had not had epilepsy?”
Results
Participants with epilepsy had fewer offspring than their unaffected relatives (mean = 1.2 vs. 1.9, p = .002), and this difference persisted among persons who had been married. Estimates of risk of epilepsy in offspring of an affected parent were higher among participants with epilepsy than among relatives without epilepsy (mean = 27.2 vs. 19.6, p = .002). Nineteen percent of participants with epilepsy responded that they would have wanted more children if they had not had epilepsy. Twenty‐five percent of participants with epilepsy responded that “the chance of having a child with epilepsy” or “having epilepsy in your family” made them less likely to want to have a child. Having these genetic concerns was significantly associated with greater genetic attribution and estimated risk of epilepsy in offspring of an affected parent.
Significance
People with epilepsy have fewer children than their biological relatives without epilepsy. Beliefs about genetic causes of epilepsy contribute to concerns and decisions to limit childbearing. These beliefs should be addressed in genetic counseling to ensure that true risks to offspring and reproductive options are well understood.
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