A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs

Rocca, María Florencia; Zintgraff, Jonathan; Dattero, María Elena; Santos, Leonardo S.; Ledesma, Martín; Vay, Carlos; Prieto, Mónica; Benedetti, Estefanía; Avaro, Martín; Russo, M.; Nachtigall, Fabiane M.; Baumeister, Elsa

doi:10.1101/2020.05.07.082925

Cited by 9 publications

(14 citation statements)

References 11 publications

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“…Natchigall et al [13] reported in nasal swab samples that five of the seven peaks, distinguishing Cov+ and Cov-groups, have a higher intensity distribution in healthy individuals. Similarly, in another study using swab samples, all the discriminant peaks possessed a higher intensity distribution for uninfected individuals than for SARS-CoV-2 contaminated patients [14]. Conversely, here, in saliva samples, discriminant MS peaks correspond mainly to up-regulation protein expression subsequent to SARS-CoV-2 infection.…”

Section: Discussionsupporting

confidence: 49%

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Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva

Costa¹,

Martin²,

Estellon³

et al. 2021

Preprint

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SARS-CoV-2 caused a large outbreak since its emergence in December 2019. The COVID-19 diagnosis became a priority to isolate and treat infected individuals in order to break the contamination chain. Currently, the reference test for COVID-19 diagnosis is the molecular detection (RT-qPCR) of the virus from nasopharyngeal swab (NPS) samples. Although this sensitive and specific test remains the gold standard, it has several limitations, such as the invasive collection method, the relative high cost and the duration of the test. Moreover, the material shortage to perform tests due to the discrepancy between the high demand for tests and the production capacities puts additional constraints on RT-qPCR. Here, we propose a PCR-free method for diagnosing SARS-CoV-2 based on Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling and machine learning (ML) models from salivary samples. Kinetic saliva samples were collected at enrollment and ten and thirty days later (D0, D10 and D30), to assess the classification performance of the ML models compared to the molecular tests performed on NPS specimens. Spectra were generated using an optimized protocol of saliva collection and successive quality control steps were developed to ensure the reliability of spectra. A total of 360 averaged spectra were included in the study. At D0, the comparison of MS spectra from SARS-CoV-2 positive patients (n=105) with healthy healthcare controls (n=51) revealed nine peaks that significantly distinguished the two groups. Among the five ML models tested, Support Vector Machine with Linear Kernel (SVM-LK) provided the best performance on the training dataset (accuracy = 85.2 %, sensitivity = 85.1 %, specificity = 85.3 %, F1-Score = 85.1 %). The application of the SVM-LK model on independent datasets confirmed it performances with 88.9% and 80.8% of correct classification for samples collected at D0 and D30, respectively. Conversely, at D10, the proportion of correct classification fallen to 64.3%. The analysis of saliva samples by MALDI-TOF MS and ML appears as an interesting supplementary tool for COVID-19 diagnosis, despite the mitigated results obtained for convalescent patients (D10).

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Section: Discussionsupporting

confidence: 49%

“…Another work has shown that the combination of MALDI-TOF MS and machine learning (ML) analysis appears to be a suitable strategy for COVID-19 diagnosis using NPS specimens [14]. The application of this strategy to serum samples succeeded to classify COVID-19 patients according to the severity of clinical symptoms [15].…”

Section: Introductionmentioning

confidence: 99%

Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva

Costa¹,

Martin²,

Estellon³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…If there is a lack of freezer facility for prior-collected gargle/saliva samples to perform RT-PCR examination, those are already known, and in that case, only prospective testing is possible. Several of the researchers are effortlessly working with numerous other researchers collecting gargle/saliva test samples and process as a demo where a PCR testing for selected swabs can be simultaneously processed ( Iles et al, 2020b ; Rocca et al, 2020 ). Such research groups have to analyze different samples also using their MALDI-ToF instrumentation with necessary reagents involved and by their all possible technical support.…”

Section: Emerging Serological Tests For Sars-cov-2mentioning

confidence: 99%

Biological characteristics and biomarkers of novel SARS-CoV-2 facilitated rapid development and implementation of diagnostic tools and surveillance measures

Ghodake

Shinde

Kadam

et al. 2021

Biosensors and Bioelectronics

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“… 45 Using MALDI-MS combined multivariate statistical analysis, Dattero et al showed the potential of MALDI-MS as a complementary diagnostic tool for discriminating SARS-CoV-2 from other viruses. 46 Overall, LC and MALDI-MS based proteomics has shown potential as a key COVID-19 research area; however, development of rapid and sensitive MS techniques along with trials in larger clinical studies are necessary to translate the beneficial aspects of MS-based proteomics in pandemics like COVID-19 disease ( Figure 1 ).…”

Section: Mass Spectrometry-based Proteomics In Covid-19mentioning

confidence: 99%

Mass Spectrometry Techniques in Emerging Pathogens Studies: COVID-19 Perspectives

Mahmud

Garrett

2020

J. Am. Soc. Mass Spectrom.

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As corona virus disease 2019 (COVID-19) is a rapidly growing public health crisis across the world, our knowledge of meaningful diagnostic tests and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still evolving. This novel coronavirus disease COVID-19 can be diagnosed using RT-PCR, but inadequate access to reagents, equipment, and a nonspecific target has slowed disease detection and management. Precision medicine, individualized patient care, requires suitable diagnostics approaches to tackle the challenging aspects of viral outbreaks where many tests are needed in a rapid and deployable approach. Mass spectrometry (MS)-based technologies such as proteomics, glycomics, lipidomics, and metabolomics have been applied in disease outbreaks for identification of infectious disease agents such as virus and bacteria and the molecular phenomena associated with pathogenesis. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is widely used in clinical diagnostics in the United States and Europe for bacterial pathogen identification. Paper spray ionization mass spectrometry (PSI-MS), a rapid ambient MS technique, has recently open a new opportunity for future clinical investigation to diagnose pathogens. Ultra-high-pressure liquid chromatography coupled high-resolution mass spectrometry (UHPLC–HRMS)-based metabolomics and lipidomics have been employed in large-scale biomedical research to discriminate infectious pathogens and uncover biomarkers associated with pathogenesis. PCR-MS has emerged as a new technology with the capability to directly identify known pathogens from the clinical specimens and the potential to identify genetic evidence of undiscovered pathogens. Moreover, miniaturized MS offers possible applications with relatively fast, highly sensitive, and potentially portable ways to analyze for viral compounds. However, beneficial aspects of these rapidly growing MS technologies in pandemics like COVID-19 outbreaks has been limited. Hence, this perspective gives a brief of the existing knowledge, current challenges, and opportunities for MS-based techniques as a promising avenue in studying emerging pathogen outbreaks such as COVID-19.

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A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs

Cited by 9 publications

References 11 publications

Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva

Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva

Biological characteristics and biomarkers of novel SARS-CoV-2 facilitated rapid development and implementation of diagnostic tools and surveillance measures

Mass Spectrometry Techniques in Emerging Pathogens Studies: COVID-19 Perspectives

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