On the Challenges for the Diagnosis of SARS-CoV-2 Based on a Review of Current Methodologies

Mattioli, Isabela A.; Hassan, Ayaz; Oliveira, Osvaldo N.; Crespilho, Frank N.

doi:10.1021/acssensors.0c01382

Cited by 90 publications

(86 citation statements)

References 229 publications

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“…As the causative virus spreads through the respiratory system, the quickest and most employed method of diagnostics is based on polymerase chain reaction (PCR) testing of nasal and throat swabs, and less commonly used, anal swabs [3,4]. However, some of the predominant limitations of PCR methods, especially during the early stages of infection (<1 week), include the time required for a positive confirmation (up to 72 h) and the high technological inputs that are needed to perform the assay itself (i.e., PCR machines, primers, molecular probes among others) [5]. Other commonly used methods rely on the analysis of serology antibodies, and although cheaper and technically less challenging than PCR, they do not provide reliable results until the second week of infection, when the IgG and IgM antibodies peak in serum samples [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…However, some of the predominant limitations of PCR methods, especially during the early stages of infection (<1 week), include the time required for a positive confirmation (up to 72 h) and the high technological inputs that are needed to perform the assay itself (i.e., PCR machines, primers, molecular probes among others) [5]. Other commonly used methods rely on the analysis of serology antibodies, and although cheaper and technically less challenging than PCR, they do not provide reliable results until the second week of infection, when the IgG and IgM antibodies peak in serum samples [5,6]. The biggest hurdle for both assays is the monetary price associated with each test.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

et al. 2021

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Coronavirus disease (COVID-19) is a contagious respiratory disease that is causing significant global morbidity and mortality. Understanding the impact of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the host metabolism is still in its infancy but of great importance. Herein, we investigated the metabolic response during viral shedding and post-shedding in an asymptomatic SARS-CoV-2 ferret model (n = 6) challenged with two SARS-CoV-2 isolates. Virological and metabolic analyses were performed on (minimally invasive) collected oral swabs, rectal swabs, and nasal washes. Fragments of SARS-CoV-2 RNA were only found in the nasal wash samples in four of the six ferrets, and in the samples collected 3 to 9 days post-infection (referred to as viral shedding). Central carbon metabolism metabolites were analyzed during viral shedding and post-shedding periods using a dynamic Multiple Reaction Monitoring (dMRM) database and method. Subsequent untargeted metabolomics and lipidomics of the same samples were performed using a Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) methodology, building upon the identified differentiated central carbon metabolism metabolites. Multivariate analysis of the acquired data identified 29 significant metabolites and three lipids that were subjected to pathway enrichment and impact analysis. The presence of viral shedding coincided with the challenge dose administered and significant changes in the citric acid cycle, purine metabolism, and pentose phosphate pathways, amongst others, in the host nasal wash samples. An elevated immune response in the host was also observed between the two isolates studied. These results support other metabolomic-based findings in clinical observational studies and indicate the utility of metabolomics applied to ferrets for further COVID-19 research that advances early diagnosis of asymptomatic and mild clinical COVID-19 infections, in addition to assessing the effectiveness of new or repurposed drug therapies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

et al. 2021

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“…Importantly, IgM levels go down post infection, while IgG levels remain the same even after 5 weeks of initial infection. 46 In addition, quantifying the concentration of IgG and IgM to determine the antibody level in patients would provide insight into the human immune response when overcoming COVID-19 infection and will be critical to epidemiology when mass vaccination occurs. As a proof of concept, we performed serological tests to quantify IgG and IgM levels in COVID-19 patient samples utilizing our biosensors.…”

Section: Resultsmentioning

confidence: 99%

Multiplexed and High-Throughput Label-Free Detection of RNA/Spike Protein/IgG/IgM Biomarkers of SARS-CoV-2 Infection Utilizing Nanoplasmonic Biosensors

et al. 2021

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To tackle the COVID-19 outbreak, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an unmet need for highly accurate diagnostic tests at all stages of infection with rapid results and high specificity. Here, we present a label-free nanoplasmonic biosensor-based, multiplex screening test for COVID-19 that can quantitatively detect 10 different biomarkers (6 viral nucleic acid genes, 2 spike protein subunits, and 2 antibodies) with a limit of detection in the aM range, all within one biosensor platform. Our newly developed nanoplasmonic biosensors demonstrate high specificity, which is of the upmost importance to avoid false responses. As a proof of concept, we show that our detection approach has the potential to quantify both IgG and IgM antibodies directly from COVID-19-positive patient plasma samples in a single instrument run, demonstrating the high-throughput capability of our detection approach. Most importantly, our assay provides receiving operating characteristics, areas under the curve of 0.997 and 0.999 for IgG and IgM, respectively. The calculated p -value determined through the Mann–Whitney nonparametric test is <0.0001 for both antibodies when the test of COVID-19-positive patients ( n = 80) is compared with that of healthy individuals ( n = 72). Additionally, the screening test provides a calculated sensitivity (true positive rate) of 100% (80/80), a specificity (true negative rate) >96% (77/80), a positive predictive value of 98% at 5% prevalence, and a negative predictive value of 100% at 5% prevalence. We believe that our very sensitive, multiplex, high-throughput testing approach has potential applications in COVID-19 diagnostics, particularly in determining virus progression and infection severity for clinicians for an appropriate treatment, and will also prove to be a very effective diagnostic test when applied to diseases beyond the COVID-19 pandemic.

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“…They can be used not only for immune sensing and genetic testing but also for alternative testing principles that do not require special biometrics. Their emergence could improve and extend the diagnostics of COVID-19, which could lead to low-cost large-scale testing methods and/or improved accuracy [ 59 ]. We believe that, with progress in research, detection technologies will be further improved.…”

Section: Discussionmentioning

confidence: 99%

Research progress in laboratory detection of SARS-CoV-2

Wang

Xiang

et al. 2021

Ir J Med Sci

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Background Nucleic acid testing is a reliable method for diagnosing viral infection in clinical samples. However, when the number of cases is huge and there are individual differences in the virus itself, the probability of false-negative results increases. With the advancement in research on the new coronavirus, new detection technologies that use serum-specific antibodies as detection targets have been developed. These detection technologies have high efficiency and shorter turnaround time, which ultimately shortens the time required for diagnosis. This article summarizes the methods that have been reported to date for the detection of the new coronavirus and discusses their principles and technical characteristics. Aims Compare the advantages and disadvantages of various SARS-CoV-2 detection methods and analyze their principles. Methods Searched reports on SARS-CoV-2 detection methods published so far, extracted the data and analyzed them. Use the primer blast function of NCBI to analyze the primers used in qRT-PCR detection. Results The detection sensitivity was the highest when nucleocapsid protein gene was used as the target, reaching 96.6%. The detection efficiency of the remaining targets ranged from 66.7% to 96.0%. Various new detection methods, like Serum specific antibody detection, can speed up the test time. However, due to the complexity of the method and higher testing requirements, it seems that it cannot be used as a complete replacement for qRT-PRC testing. Conclusions With the advancement of technology and the improvement of methods, the detection methods of SARSCoV-2 have become more mature. These advances provided great help to the detection of SARS-CoV-2.

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On the Challenges for the Diagnosis of SARS-CoV-2 Based on a Review of Current Methodologies

Cited by 90 publications

References 229 publications

Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

Multiplexed and High-Throughput Label-Free Detection of RNA/Spike Protein/IgG/IgM Biomarkers of SARS-CoV-2 Infection Utilizing Nanoplasmonic Biosensors

Research progress in laboratory detection of SARS-CoV-2

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