Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts

Cardozo, Karina Helena Morais; Lebkuchen, Adriana; Okai, Guilherme Gonçalves; Schuch, Rodrigo Andrade; Viana, Luciana Godoy; Olive, Aline Nogueira; Lazari, Carolina dos Santos; Fraga, Ana; Granato, Celso Francisco Hernandes; Pintão, Maria Carolina; Carvalho, Valdemir Melechco

doi:10.1038/s41467-020-19925-0

Cited by 95 publications

(125 citation statements)

References 65 publications

(79 reference statements)

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“…This study also reported the two peptides were detected in upper respiratory tract swabs of patients who have symptomatically recovered from SARS-CoV2 and had tested negative for RT-PCR analyses, demonstrating the potential of the MS approach to diagnosis asymptomatic SARS-CoV2 in patients. A larger study of close to 1000 specimens, employing the PRM strategy, detected peptides of SARS-CoV-2 nucleocapsid protein both qualitatively and quantitatively by incorporating 15N-labelled standards, in up to 84% of the positive cases with up to 97% specificity [ 28 ]. In this study, the use of a robotic sample handler enabled the analysis of 4 samples every 10 minutes.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry analytical responses to the SARS-CoV2 coronavirus in review

Griffin¹,

Downard²

2021

TrAC Trends in Analytical Chemistry

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This article reviews the many and varied mass spectrometry based responses to the SARS-CoV2 coronavirus amidst a continuing global healthcare crisis. Although RT-PCR is the most prevalent molecular based surveillance approach, improvements in the detection sensitivities with mass spectrometry coupled to the rapid nature of analysis, the high molecular precision of measurements, opportunities for high sample throughput, and the potential for in-field testing, offer advantages for characterising the virus and studying the molecular pathways by which it infects host cells. The detection of biomarkers by MALDI-TOF mass spectrometry, studies of viral peptides using proteotyping strategies, targeted LC-MS analyses to identify abundant peptides in clinical specimens, the analysis of viral protein glycoforms, proteomics approaches to understand impacts of infection on host cells, and examinations of point-of-care breath analysis have all been explored. This review organises and illustrates these applications with reference to the many studies that have appeared in the literature since the outbreak. In this respect, those studies in which mass spectrometry has a major role are the focus, and only those which have peer-reviewed have been cited.

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Section: Discussionmentioning

confidence: 99%

Mass spectrometry analytical responses to the SARS-CoV2 coronavirus in review

Griffin¹,

Downard²

2021

TrAC Trends in Analytical Chemistry

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“…For establishing workflows to evaluate virus-specific peptides, three published cell culture datasets [ 22 – 24 ] which used SARS-COV2 infected Vero cell lines were chosen, along with five clinical datasets [ 26 – 29 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

“…The third dataset was obtained from the Rivera group (PXD020394) comparative quantitative proteomic analysis from oro- and naso-pharyngeal swabs used for COVID-19 diagnosis was performed. Further, unanalyzed oro/nasopharyngeal data from Cardozo et al [ 25 ] (PXD025214) as well as a nasopharyngeal swab dataset from Bankar et al [ 30 ] (PXD023016) were interrogated for the presence of our proposed targets. Datasets derived from COVID-19 patient lung biopsies (PXD018094) and bronchoalveolar lavage fluid (BALF) (PXD022085) were analyzed to determine the utility of our workflow to identify SARS-CoV-2 in clinically relevant sample types.…”

Section: Methodsmentioning

confidence: 99%

“…In order to evaluate the most robustly detectable SARS-CoV-2 peptides, and make the detection of these viral peptides in human samples in a clinical setting all the more feasible, we set out to examine proteomic datasets from three cell culture-based studies [ 22 – 24 ] and seven clinical studies [ 25 – 30 ]. We utilized automated workflows implemented in the Galaxy platform and made accessible via the European Galaxy public instance to first identify as many SARS-CoV-2 peptides possible in all samples, creating a master list of SARS-CoV-2 peptides identified across the samples.…”

Section: Introductionmentioning

confidence: 99%

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A rigorous evaluation of optimal peptide targets for MS-based clinical diagnostics of Coronavirus Disease 2019 (COVID-19)

et al. 2021

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Background The Coronavirus Disease 2019 (COVID-19) global pandemic has had a profound, lasting impact on the world's population. A key aspect to providing care for those with COVID-19 and checking its further spread is early and accurate diagnosis of infection, which has been generally done via methods for amplifying and detecting viral RNA molecules. Detection and quantitation of peptides using targeted mass spectrometry-based strategies has been proposed as an alternative diagnostic tool due to direct detection of molecular indicators from non-invasively collected samples as well as the potential for high-throughput analysis in a clinical setting; many studies have revealed the presence of viral peptides within easily accessed patient samples. However, evidence suggests that some viral peptides could serve as better indicators of COVID-19 infection status than others, due to potential misidentification of peptides derived from human host proteins, poor spectral quality, high limits of detection etc. Methods In this study we have compiled a list of 636 peptides identified from Sudden Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples, including from in vitro and clinical sources. These datasets were rigorously analyzed using automated, Galaxy-based workflows containing tools such as PepQuery, BLAST-P, and the Multi-omic Visualization Platform as well as the open-source tools MetaTryp and Proteomics Data Viewer (PDV). Results Using PepQuery for confirming peptide spectrum matches, we were able to narrow down the 639-peptide possibilities to 87 peptides that were most robustly detected and specific to the SARS-CoV-2 virus. The specificity of these sequences to coronavirus taxa was confirmed using Unipept and BLAST-P. Through stringent p-value cutoff combined with manual verification of peptide spectrum match quality, 4 peptides derived from the nucleocapsid phosphoprotein and membrane protein were found to be most robustly detected across all cell culture and clinical samples, including those collected non-invasively. Conclusion We propose that these peptides would be of the most value for clinical proteomics applications seeking to detect COVID-19 from patient samples. We also contend that samples harvested from the upper respiratory tract and oral cavity have the highest potential for diagnosis of SARS-CoV-2 infection from easily collected patient samples using mass spectrometry-based proteomics assays.

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“…Additional techniques such as tandem MS [32] , [33] , lateral flow immunoassay [34] , [35] , [36] , and few other enzymatic assays are established for the diagnosis of COVID-19 [37] , [38] , [39] , [40] , [41] . Tandem MS is a sophisticated technique operated by highly skilled experts and it requires relatively more time for sample preparation, data acquisition, and processing.…”

Section: Rt-lamp-based Covid-19 Diagnosismentioning

confidence: 99%

A concise discussion on the potential spectral tools for the rapid COVID-19 detection

Mohanty

Fatrekar

Krishnan

et al. 2021

Results in Chemistry

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Developing robust methods to detect the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a causative agent for the current global health pandemic, is an exciting area of research. Nevertheless, the currently used conventional reverse transcription-polymerase chain reaction (RT-PCR) technique in COVID-19 diagnosis endures with some inevitable limitations. Consequently, the establishment of rapid diagnostic tools and quick isolation of infected patients is highly essential. Furthermore, the requirement of point-of-care testing is the need of the hour. Considering this, we have provided a brief review of the use of very recently reported robust spectral tools for rapid COVID-19 diagnosis. The spectral tools include, colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), with the admittance of principal component analysis (PCA) and machine learning (ML) for meeting the high-throughput and fool-proof diagnostic platforms for the detection of SARS-CoV-2, are reviewed. Recently, these techniques have been readily applied to screen a large number of suspected patients within a short period and they demonstrated higher sensitivity for the detection of COVID-19 patients from unaffected human subjects.

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Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts

Cited by 95 publications

References 65 publications

Mass spectrometry analytical responses to the SARS-CoV2 coronavirus in review

Mass spectrometry analytical responses to the SARS-CoV2 coronavirus in review

A rigorous evaluation of optimal peptide targets for MS-based clinical diagnostics of Coronavirus Disease 2019 (COVID-19)

A concise discussion on the potential spectral tools for the rapid COVID-19 detection

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