Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study.

BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection.

Background: Performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance in screening for SARS-CoV-2 is not well established. We aimed to evaluate performance of Ag-RDT for detection of SARS-CoV-2 for symptomatic and asymptomatic participants. Methods: Participants >2 years old across the United States enrolled in the study between October 2021 and February 2022. Participants completed Ag-RDT and molecular testing (RT-PCR) for SARS-CoV-2 every 48 hours for 15 days. This analysis was limited to participants who were asymptomatic and tested negative on their first day of study participation. Onset of infection was defined as the day of first positive RT-PCR result. Sensitivity of Ag-RDT was measured based on testing once, twice (after 48-hours), and thrice (after 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status. Results: In total, 5,609 of 7,361 participants were eligible for this analysis. Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDT twice 48-hours apart resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Excluding singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower at 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with testing three times at 48-hour intervals. Discussion: Performance of Ag-RDT was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.

Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic.

Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) for programmable capture and concentration of specific RNAs from complex mixtures. The target bound TtCsm complex generates two cyclic oligoadenylates (i.e., cA3 and cA4) that allosterically activate ancillary nucleases. We show that both Can1 and Can2 nucleases cleave single-stranded RNA, single-stranded DNA, and double-stranded DNA in the presence of cA4. We integrate the Can2 nuclease with type III-A RNA capture and concentration for direct detection of SARS-CoV-2 RNA in nasopharyngeal swabs with 15 fM sensitivity. Collectively, this work demonstrates how type-III CRISPR-based RNA capture and concentration simultaneously increases sensitivity, limits time to result, lowers cost of the assay, eliminates solvents used for RNA extraction, and reduces sample handling.

Excessive iodine in iodized household salt in Nepal.

Iodine is an essential trace element required for the regulation of physiological processes involving the thyroid gland. However, inadequate and excessive intake of iodine are responsible for health problems, such as iodine deficiency disorders, hypothyroidism, hyperthyroidism, thyroiditis, thyroid papillary cancer, and thyrotoxicosis. The Universal Salt Iodization (USI) program has become successful in providing supplemental iodine at the population level globally. Packaging quality, fortification level, and transportation and storage conditions of iodized salt determine the availability of iodine. Previous studies have reported severe health issues caused by excessive iodine intake after the implementation of the USI program. To understand the levels of iodine, we collected 2117 household salt samples from seven districts of Nepal and tested them for iodine content; among them, 98.1% were iodized. Overall median concentration of iodine was 53.9 ppm (range: 43.5-61.4 ppm). The majority (67.2%) of samples had iodine in the range of 45-75 ppm. Approximately 0.9% of samples had inadequate, 13.3% contained adequate, and 83.9% had excessive iodine than the World Health Organization-recommended value. Iodine content varied among the sampling districts and seasons, to some extent. Our study confirmed that iodized salt is widely used in Nepal and is excessively iodized. Excessive intake of iodine through iodized salt requires further attention by policy makers. The iodine level may need adjustment to address the health impact.

Charge doping to flat AgF2 monolayers in a chemical capacitor setup.

Flat monolayers of silver(II) fluoride, which could be obtained by epitaxial deposition on an appropriate substrate, have been recently predicted to exhibit very strong antiferro-magnetic superexchange and to have large potential for ambient pressure superconductivity if doped to an optimal level. It was shown that AgF2 could become a magnetic glue-based superconductor with a critical superconducting temperature approaching 200 K at optimum doping. In the current work we calculate the optimum doping to correspond to 14% of holes per formula unit, i.e. quite similar to that for oxocuprates(II). Furthermore, using DFT calculations we show that flat [AgF2] single layers can indeed be doped to a controlled extent using a recently proposed "chemical capacitor" setup. Hole doping associated with the formation of Ag(III) proves to be difficult to achieve in the setup explored in this work as it falls at the verge of charge stability of fluoride anions and does not affect the d(x2 - y2) manifold. However, in the case of electron doping, manipulation of different factors - such as the number of dopant layers and the thickness of the separator - permits fine tuning of the doping level (and concomitantly TC) all the way from the underdoped to overdoped regime (in a similar manner to chemical doping for the Nd2CuO4 analogue).

Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic.

Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we make two major advances that simultaneously limit sample handling and significantly enhance the sensitivity of SARS-CoV-2 RNA detection directly from patient samples. First, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) for programmable capture and concentration of specific RNAs from complex mixtures. The target bound TtCsm complex primarily generates two cyclic oligoadenylates (i.e., cA3 and cA4) that allosterically activate ancillary nucleases. To improve sensitivity of the diagnostic, we identify and test several ancillary nucleases (i.e., Can1, Can2, and NucC). We show that Can1 and Can2 are activated by both cA3 and cA4, and that different activators trigger changes in the substrate specificity of these nucleases. Finally, we integrate the type III-A CRISPR RNA-guided capture technique with the Can2 nuclease for 90 fM (5x104 copies/ul) detection of SARS-CoV-2 RNA directly from nasopharyngeal swab samples.

Acute-onset chronic inflammatory demyelinating polyneuropathy after COVID-19 infection and subsequent ChAdOx1 nCoV-19 vaccination.

SARS-COV-2 predominantly results in a respiratory illness. However, it has also been associated with a wide range of neurological disorders including a broad range of immune neuropathies. These immune neuropathies associated with SARS-COV2 infection include Guillain-Barré syndrome (GBS), recurrent GBS and exacerbation of pre-existing chronic inflammatory demyelinating polyneuropathy (CIDP). We describe a case with acute-onset CIDP presenting with three relapses of demyelinating polyradiculoneuropathy, the third relapse occurring in the 8 week of illness following a previous COVID-19 infection and a recent COVID-19 vaccination with ChAdOx1 nCoV-19 and high COVID-19 antibody level. In our knowledge, this is the ever reported case of acute-onset CIDP associated with COVID-19 vaccine and high COVID-19 antibody level.

Cladophialophora bantiana brain abscess with lymphadenitis.

Cerebral phaeohyphomycosis refers to central nervous system infection by dematiaceous mould or by dark walled fungi which contain the dark pigment melanin in their cell wall which adds to the virulence of fungus. These dematiaceous fungi can cause a variety of central nervous infections including invasive sinusitis, brain abscess, meningitis, myelitis and arachnoiditis. Cladophialophora bantiana among these dematiaceous fungi is the most common cause of brain abscess in immunocompetent and immunocompromised individuals and is known to occur worldwide though is predominantly reported from subtropical regions especially the Asian subcontinent. It is difficult to differentiate these abscesses radiologically from high-grade gliomas, primary central nervous system lymphoma or other infections including toxoplasmosis, nocardiosis, tuberculosis and listeriosis. We describe a 19-year-old male patient with a cerebral abscess caused by C. bantiana where the diagnosis could be suspected by typical MR spectroscopic findings and by identifying the fungus from a lymph node biopsy.

Review of analytical performance of COVID-19 detection methods.

In the recent SARS-CoV-2 pandemic, public health experts have emphasized testing, tracking infected people, and tracing their contacts as an effective strategy to reduce the spread of the virus. Several diagnostic methods are reported for detecting the coronavirus in clinical, research, and public health laboratories. Some tests detect the infection directly by detecting the viral RNA and other tests detect the infection indirectly by detecting the host antibodies. A diagnostic test during the pandemic should help make an appropriate clinical decision in a short period of time. Recently reported diagnostic methods for SARS-CoV-2 have varying throughput, batching capacity, requirement of infrastructure setting, analytical performance, and turnaround times ranging from a few minutes to several hours. These factors should be considered while selecting a reliable and rapid diagnostic method to help make an appropriate decision and prompt public health interventions. This paper reviews recent SARS-CoV-2 diagnostic methods published in journals and reports released by regulatory agencies. We compared the analytical efficiency including limit of detection, sensitivity, specificity, and throughput. In addition, we also looked into ease of use, affordability, and availability of accessories. Finally, we discuss the limitations of the methods and provide our perspectives on priorities for future test development.

Layer-Dependent Electronic Structure Changes in Transition Metal Dichalcogenides: The Microscopic Origin.

We have examined the electronic structure evolution in transition metal dichalcogenides MX2 where M = Mo, W and X = S, Se, and Te. These are generally referred to as van der Waals materials on the one hand, yet one has band gap changes as large as 0.6 eV with thickness in some instances. This does not seem to be consistent with a description where the dominant interactions are van der Waals interactions. Mapping onto a tight binding model allows us to quantify the electronic structure changes, which are found to be dictated solely by interlayer hopping interactions. Different environments that an atom encounters could change the Madelung potential and therefore the onsite energies. This could happen while going from the monolayer to the bilayer as well as in cases where the stackings are different from what is found in 2H structures. These effects are quantitatively found to be negligible, enabling us to quantify the thickness-dependent electronic structure changes as arising from interlayer interactions alone.