December 11, 2020 I Two-thirds of COVID-19 patients lose sense of taste and smell, nanoPCR technology for diagnosis, biomarkers of blood vessel damage in children, sore eyes significant ocular symptom, Nanopore sequencing technology, understanding viral persistence and immune responses, and IgA antibodies dominate early neutralizing response. Plus: New testing method detects gene expression patterns, lung sound recording system prototype, healthcare workers immunity lasts several months, and combining antibody assays may yield most accurate results.
Research News
University of California (UC) Santa Cruz scientists have developed a new serological assay for the detection of SARS-CoV-2 antibodies that provides rapid results and is as accurate as the most reliable antibody tests currently available. The new method, called biolayer interferometry immunosorbent assay (BLI-ISA), provides quantitative measurements of antibodies in blood plasma in under 20 minutes. This new BLI-ISA uses optical biosensor technology. The team explains that their new method could provide a standardized way to evaluate vaccine candidates, and they are hoping to use the new assay to conduct a surveillance study to assess the prevalence of COVID-19 infections within the Santa Cruz community. Their work is published in Scientific Reports. DOI:10.1038/s41598-020-78895-x
Nearly two-thirds of COVID-19 patients admitted to an Italian hospital reported a loss of smell and taste, according to a new study published in Neurology Clinical Practice. The study included 93 patients (average age of 63) who were admitted to the COVID-19 unit in March of 2020, and 58 of those patients (63%) stated that they lost their sense of taste and smell when interviewed about their symptoms. Moreover, 22% of those patients reported that this was their first symptom with an average duration of 25 to 30 days. The researchers then analyzed bloodwork of these patients and determined that those with compromised sense of smell had lower neutrophil counts, which was 29% less when compared to those with a normal sense of smell. DOI:10.1212/CPJ.0000000000001029
A new nanoPCR technology that can accurately diagnose SARS-CoV-2 infection in under 20 minutes has been developed by a team of Korean researchers. The technique uses the same underlying principles as reverse transcription polymerase chain reaction (RT-PCR), the gold standard test method for COVID-19, to detect viral RNA, but it provides a result much faster using hybrid nanomaterials and is much more compact. The researchers tested nanoPCR under clinical settings on 150 subjects with or without COVID-19 and provided an accurate diagnosis in all patients (75 positives and 75 negative samples). The level of sensitivity and specificity was found to be equivalent to the conventional RT-PCR and the whole process took 17 minutes on average. The researchers also showed the possibility of loading multiple samples from multiple patients at once by applying a Ferris wheel system. This work is published in Nature Biomedical Engineering. DOI:10.1038/s41551-020-00654-0
Researchers from the Children’s Hospital of Philadelphia (CHOP) have found elevated levels of a biomarker related to blood vessel damage in children with COVID-19, even in those with mild to no symptoms. In this study, published in Blood Advances, they also found that in a cohort of 22 pediatric patients with COVID-19, 86% met the clinical and diagnostic criteria for thrombotic microangiopathy (TMA), which is a syndrome that involves clotting in the small blood vessels. The researchers explain that they do not yet know the implications of this elevated biomarker in children with COVID-19 but suggest further testing and monitoring of children with SARS-CoV-2 to gain a better understanding. They add that these findings show that there is much more to learn about the virus and its short and long-term impacts on health. DOI:10.1182/bloodadvances.2020003471
Sore eyes may be the most significant ocular symptom of COVID-19, finds new research published in BMJ Open Ophthalmology. Anglia Ruskin University (ARU) researchers looked at questionnaire responses from 83 individuals diagnosed with COVID-19 to evaluate reported symptoms. They found that sore eyes were the most commonly reported symptom, with 16% reporting this problem and only 5% stating that they had this condition prior to infection. 81% of the respondents reported ocular issues within two weeks of COVID-19 symptom onset, however 80% of those persons stated that these eye problems lasted less than two weeks. The researchers suggest that sore eyes replace conjunctivitis on the list of possible COVID-19 symptoms, as it is important to differentiate between an ocular symptom and a possible bacterial infection of the eye. DOI:10.1136/bmjophth-2020-000632
Researchers from Sydney have published an analytical validation and best practice guidelines for Nanopore sequencing of SARS-CoV-2 in a new paper published in Nature Communications. Their analysis demonstrated the Nanopore sequencing method to be highly accurate—variants were detected with over 99% sensitivity and precision in 157 SARS-CoV-2 positive patient samples. The researchers explain that this coronavirus genome sequencing, that provides results in under four hours, has the potential to track virus transmission and origins to understand how cases of COVID-19 are linked. They hope that this analysis and best practice guidelines will assist public heath teams around the globe to adopt this technology and improve contact tracing through real time genomic transmission studies. DOI:10.1038/s41467-020-20075-6
COVID-19 patients may develop a wide range of symptoms that evolve over time. This prolonged infection, or ‘long COVID’, was further investigated by researchers in Geneva by reviewing COVID-19 symptom evolution and persistence in an outpatient setting from the first day of diagnosis through day 30 to 45. They determined that these patients developed an array of symptoms that evolved over time. Fatigue, dyspnea, and loss of taste or smell were the most prominent symptoms that persisted. The researchers believe that public health messages about these persistent symptoms could encourage some to comply with recommended measures to slow the spread and avoid infection. This research is published in the Annals of Internal Medicine. DOI:10.7326/M20-5926
A new Wuhan study, published in the Annals of Internal Medicine, aimed to gain a better understanding of viral persistence and immune responses in COVID-19 patients. The researchers examined over 3,000 COVID-19 patients admitted to Tongji hospitals to describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and prognosis. They found that the rate of viral PCR positivity peaked with the initial few days and seroconversion rates peaked within four to five weeks. Dynamic laboratory index changes corresponded to clinical signs, the recovery process, and disease severity in most cases. They suggest that further work is urgently needed to provide a better understanding of the potential effects of COVID-19, immune responses to the virus, and these interactions during the acute and convalescent phases of infection. DOI:10.7326/M20-3337
IgA antibodies dominate the early neutralizing antibody response to SARS-CoV-2, finds a new study published in Science Translational Medicine. Researchers studied samples from over 150 COVID-19 patients with mild to severe symptoms and found that IgA concentrations were higher than IgG and IgM concentrations in the first 3 to 4 weeks after symptom onset and then waned, however, IgA antibodies persisted in saliva for several more weeks. In a separate study, the researchers cloned antibodies taken from recovered COVID-19 patients and discovered that the dimeric form of IgA was fifteen times better at neutralizing the SARS-CoV-2 virus then the monomeric form. Based on these findings, they suggest vaccine development that induces an IgA response and IgA-based tests to detect infection at early stages. DOI:10.1126/scitranslmed.abd2223
A paper-based electrochemical sensor that detects the presence of SARS-CoV-2 in less than five minutes has been developed at the University of Illinois Grainger College of Engineering. This new biosensor uses graphene, which exhibits unique properties that make it ideal for sensitive electrochemical sensors, with an electrical read-out setup to selectively detect the presence of viral RNA. When testing the performance of this sensor on positive and negative COVID-19 samples, it showed a significant increase in the voltage of positive samples compared to negative ones and was able to differentiate viral RNA loads in these samples. This work is detailed in ACS Nano. DOI:10.1021/acsnano.0c06392
In a five-month longitudinal study, researchers followed 254 COVID-19 patients, who had varying degrees of severity with infection, and investigated antibody responses in these patients. They found that IgA and IgM antibodies to SARS-CoV-2 disappeared rather quickly and IgG antibodies lasted longer, however, they documented a slow decline in this antibody class as well, even in those who recovered from severe COVID-19 disease. Interestingly, they detected a higher ratio of antibodies that react to the viral spike protein complex in those patients with mild infection compared to those with severe symptoms, concluding that this finding could explain why these individuals never developed severe infection. The authors of this study, published in Science Immunology, also suggest that their findings may indicate an underestimation of how many people have previously been infected with COVID-19 and raise the question of how long a vaccine will offer protection against the virus. DOI:10.1126/scitranslmed.abe024
Research led at the University of California, San Francisco (UCSF) has led to a new COVID-19 testing approach that detects distinct patterns of immune gene expression in SARS-CoV-2 positive patients, rather than detecting the virus itself. The UCSF scientists created three proof-of-concept versions of the new test based on readouts of gene activity from three, 10, and 27 key genes. The tests independently detected infection in clinically confirmed cases, increasing in sensitivity with the number of genes included. The researchers also discovered that the gene expression patterns in COVID-19 patients indicated that the virus may suppress immune reactions in the early stages of infection, which likely allows the virus to spread before patients experience any symptoms. This research is published in Nature Communications. DOI:10.1038/s41467-020-19587-y
A new CRISPR-based assay for COVID-19 uses a smartphone camera to deliver accurate results in less than 30 minutes. In this new test, the Cas13 protein is combined with an RNA-based probe that becomes florescent when cleaved. The patient’s sample is placed in a device that attaches to a smartphone and if the sample contains SARS-CoV-2 RNA, the Cas13 will be activated and cleave the probe, which causes the emission of a florescent signal that is detected by the smartphone camera. This new test not only provides a positive or negative result, but it also measures the viral load of SARS-CoV-2 in the sample. This new work is published in Cell. DOI:10.1016/j.cell.2020.12.001
Researchers from the Institute of Biomedicine of Seville (IBIS) have identified six biochemical biomarkers of COVID-19 infection and have published their work in Clinical Laboratory. This study, a joint effort with specialists at the Clinical Biochemistry service, evaluated routine blood tests of more than 200 patients in the emergency department to detect infection. They analyzed blood lymphocyte and eosinophil count, ferritin levels, lactate dehydrogenase, C-reactive protein, and d-dimer in plasma as the six established criteria linked to SARS-CoV-2 infection, and 91% of the COVID-19 positive patients met one or more of these biomarker criteria. The researchers believe that it is possible to rule out COVID-19 infection with a high degree of certainty in patients who do not meet any of these criteria. DOI:10.7754/Clin.Lab.2020.200522
Combining antibody assays may yield the most accurate results for SARS-CoV-2 antibody testing, according to a new study published in PLOS ONE. The study, led by the University of Tartu, assessed nine different antibody tests that were most widely used during the COVID-19 outbreak in the spring to test 97 patients from Saaremaa with confirmed cases. They discovered that the sensitivity of the tests was lower than stated by the producers and, for some tests, the positivity rates in asymptomatic COVID-19 patients was about two times lower than in those displaying several symptoms. The researchers suggest combining several antibody tests for the most accurate results, such as a test sensitive to antibodies to the nucleocapsid and a test that detects antibodies to the spike protein. DOI:10.1371/journal.pone.0237548
Industry News
Thermo Fisher Scientific announced the availability of a new direct from saliva PCR test for COVID-19 to enable widespread, high-frequency surveillance testing. The Applied Biosystems TaqCheck SARS-CoV-2 Fast PCR Assay uses raw saliva samples and simplifies lab workflows using instruments that are widely available globally to deliver reliable data quickly. The company also introduced the Safe Campus Reopening Program to subsidize the cost of the test for U.S. colleges, universities and post-secondary institutions. Availability of this program coincides with recent guidance issued by the Centers for Disease Control and Prevention (CDC) that calls for expanded COVID-19 surveillance using PCR-based tests with turnaround times within 24-48 hours. By performing the test directly from raw saliva and eliminating the need for equipment, materials, time and labor associated with nucleic acid extraction, the TaqCheck SARS-CoV-2 Fast PCR Assay helps labs meet the CDC turnaround time recommendations. Press release.
FDA has issued an expanded Emergency Use Authorization (EUA) for the Rheonix COVID-19 MDx Assay and now allows the use of saliva as an approved sample type. The Rheonix COVID-19 MDx Assay is processed on the fully automated Rheonix Encompass MDx workstation using proprietary Rheonix CARD cartridge technology. The system requires minimal training to use and can be quickly installed in critical locations of immediate need. It provides same-day results and is highly scalable, enabling laboratories to move from outsourcing their COVID-19 testing to providing same- or next-day test results for their communities or regions. Rheonix has supported customers’ expanding testing needs by significantly scaling its manufacturing capacity, committing reagent availability to support its customers’ 24/7 testing requirements. Press release.
The NIH, under the Rapid Acceleration of Diagnostics-Underserved Populations Initiative (RADx-UP), has awarded a $1.6 million grant to fund a new research project to study whether interventions that have been effective at engaging high-risk populations in HIV/AIDS testing can be adapted to mitigate COVID-19. The project involves a randomized trial with over 580 residents of Essex County in New Jersey, who are medically or socially vulnerable to COVID-19. The researchers will identify factors that promote compliance with testing and precautionary measures such as hand washing, social distancing and self-quarantining. A social work professor from the University of Illinois Urbana-Champaign is partnering with the New Jersey Community Research Initiative for this project. Press Release
A study led by researchers at the University of Oxford finds that healthcare workers who contracted COVID-19 could have immunity that lasts several months. The researchers tested over 12,000 healthcare workers in England routinely for infection with SARS-CoV-2 and for antibodies against the virus. They found that those workers who tested positive for antibodies at the beginning of the study were protected against reinfection for at least six months. Out of more than 1,400 antibody-positive participants in the study, only three subsequently tested positive for COVID-19 and none of them had any symptoms. These findings are published as a pre-print on medRxiv. Press Release
A team from Graz University of Technology has developed a prototype of a lung sound recording system (LSRS) that allows for high-quality recordings of lung sounds, which could be used to detect or objectively assess lung diseases or pathological lung conditions. The LSRS is multi-channel and equipped with powerful micro-electromechanical microphones (MEMS). The researchers hope to further develop the system for screening of COVID-19 patients, however, adaptation of the system to COVID-19 typical lung sounds requires appropriate recording facilities for infected patients. They have applied for funding to expand upon this technology to assist in better diagnostics and screening for COVID-19 related lung injuries and diseases. Press Release
Two-Photon Research (TPR), based in Montreal, announces CAST, a diagnostics platform that uses TPR’s patented Aptamer Molecular Photonic Beacon (AMPB) that photonically interfaces with smartphones. The first application of CAST is for detecting COVID-19. The test uses a saliva sample, and if the virus is present, the AMPB binds to the spike protein of SARS-CoV-2 and responds to the smartphone’s LED flash. The light emitted by the AMPD is then detected by the smartphone’s CMOS sensors. The smartphone displays the results instantly and stores the results along with time and GPS information if needed. Press Release
Rheonix has received expanded Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) for the Rheonix COVID-19 MDx Assay and now allows the use of saliva as an approved sample type. The fully automated sample-to-answer assay was initially authorized for use on respiratory samples under EUA in April. The assay provides same-day results and is highly scalable, enabling laboratories to move from outsourcing their COVID-19 testing to providing quick results for their communities. Press Release