Highlights
- •Mass spectrometry complements RT-PCR in COVID-19 diagnostics.
- •Meta-analysis of mass spectrometry diagnostics for COVID-19 shows accuracy of 87%.
- •Diagnosis in admissions settings is a promising use-case for mass spectrometry.
- •Future work should focus on validating features and protocols across laboratories.
Abstract
Background
Method
Findings
Conclusions
Abbreviations:
AUROC (Area Under Receiver Operating Characteristic), DI (Direct Injection), FAIMS (high-Field Asymmetric-waveform Ion-Mobility Spectrometry), GC (Gas Chromatography), ESI (Electrospray Ionization), HESI (Heated Electrospray Ionization), IMS (Ion Mobility Spectrometry), LC (Liquid Chromatography), nLC (nano-Liquid Chromatography), MALDI (Matrix Assisted Laser Desorption Ionization), NMR (Nuclear Magnetic Resonance), QTOF (Quadrupole Time of Flight), ROC (Receiver Operating Characteristic), RT-PCR (Polymerase Chain Reaction combined with Reverse Transcription), TFC (Turbulent Flow Chromatography), TOF (Time of Flight), UHPLC (Ultra High pressure Liquid Chromatography)Keywords
1. Introduction
1.1 Rationale
- Yüce M.
- Filiztekin E.
- Özkaya K.G.
1.2 Objectives
2. Methods
2.1 Information sources and search strategy
2.2 Study selection
2.3 Data collection process
2.4 Risks of bias and applicability
2.5 Diagnostic accuracy measurements including meta-analysis of diagnostic accuracy
2.6 Statistical tools
- R Core Team
- RStudio Team
Mark Stevenson with contributions from Telmo Nunes and Cord Heuer and Jonathon Marshall and Javier Sanchez and Ron Thornton and Jeno Reiczigel and Jim Robison-Cox and Paola Sebastiani and Peter Solymos and Kazuki Yoshida and Geoff Jones and Sarah Pirikahu. epiR: Tools for the Analysis of Epidemiological Data. 2017. https://cran.r-project.org/package=epiR (accessed May 14, 2021).
3. Results
3.1 Study characteristics

Study | Country | Total COVID-19 positive/negative participants | Method | Sample | Main differentiators |
---|---|---|---|---|---|
Host-targeted approaches | |||||
Maras (2021) [ [20] ] | India | 120/ 120 | LC-MS/MS | Nasopharyngeal Swab | MX1 and WARS proteins |
Rocca (2021) [ [21] ]
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. J Virol Methods. 2020; 286https://doi.org/10.1016/j.jviromet.2020.113991 | Argentina | 123/188 | MALDI-TOF-MS | Nasopharyngeal swab | Various m/z features, non-virus |
Yan (2021) [ [35] ] | China | 146/152 | MALDI-TOF MS | Serum | Peptides linked to amyloid fibres, neutrophils and inflammatory/immune response |
Garza (2021) [ [22] ]
Rapid screening of COVID-19 directly from clinical nasopharyngeal swabs using the MasSpec Pen. Anal Chem. 2021; (published online Aug 25)https://doi.org/10.1021/acs.analchem.1c01937 | Brazil/USA | 74/194 | ESI-MS | Nasopharyngeal swab | PE, LysoPE and ceramides |
Berna (2021) | USA | 22/27 | GCxGC-MS | Breath | Octanal, heptanal, nonanal |
Ruszkiewicz (2021) [ [23] ]
Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study. EClinicalMedicine. 2020; https://doi.org/10.1016/j.eclinm.2020.100609 | Germany/UK | 67/31 | GC-IMS | Breath | Ethanal, octanal, acetone, butanone, methanol, isoprene, heptanal, propanol, propanal |
Wadah (2021) [ [24] ] | UK | 52/29 | GC-MS | Breath | Benzaldehyde, 1-propanol, 3-6 methylundecane, camphene, beta-cubene, iodobenzene |
Grassin-Delyle (2020) [ [25] ] | France | 28/12 | Heated transfer line to QTOF MS | Breath | Methypent-2-anal, 2,4-octadiene, 1 chloroheptane, nonanal |
Fraser (2020) [ [18] ] | Canada | 10/20 | DI-MS/LC-MS/MS plus NMR | Plasma | Arginine/kurenine ratio and creatinine |
Delafiori (2020) [ [26] ] | Brazil | 442/373, | HESI-MS | Plasma | Cholesterol/LysoPCs |
Kimhofer (2020) [ [27] ] | Australia | 17/25 | UHPLC-MS plus NMR | Plasma | Kynurenine/tryptophan ratio, glutamine/glutamate ratio |
Gray (2021) [ [28] ]
Diagnostic potential of the plasma lipidome in infectious disease: application to acute sars-cov-2 infection. Metabolites. 2021; 11https://doi.org/10.3390/metabo11070467 | Australia/Spain | 332/159 | UHPLC-MS | Plasma | Lipid panel (PE, PL, LPC, HCER, CER, DCER) |
Spick (2021) [ [29] ] | UK | 30/37 | UHPLC-MS | Skin swab | Odd-chain triglycerides |
Delafiori* (2021) [ [30] ] | Brazil | 64/37 | HESI-MS | Skin swab | Oleamide, N-acylethanolamines, N-acylaminoacids, glycerolipids |
Frampas* (2021) [ [31] ]
Untargeted saliva metabolomics reveals COVID-19 severity. medRxiv. 2021; https://doi.org/10.1101/2021.07.06.21260080 | UK | 47/28 | UHPLC-MS | Saliva | Phenylalanine, unidentified m/z |
Untargeted approaches | |||||
Tran (2021) [ [32] ] | USA | 107/92 | MALDI-TOF-MS | Nasopharyngeal swab | Various m/z, not identified |
Nachtigall (2020) [ [33] ] | Chile | 211/151 | MALDI-MS | Nasopharyngeal swab | Various m/z, not identified |
Deulofeu (2021) [ [34] ] | Spain | 60/176 | MALDI-TOF-MS | Nasopharyngeal swab | Various m/z, not identified |
Virus-targeted approaches | |||||
Cardozo (2020) [ [36] ] | Brazil | 540/445 | TFC-MS | Nasopharyngeal swab | Virus proteins |
Chivte (2021) [ [37] ]
MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19. J Mass Spectrom Adv Clin Lab. 2021; https://doi.org/10.1016/j.jmsacl.2021.09.001 | USA | 30/30 | MALDI-TOF-MS | Saliva | Virus spike protein S2 |
Hober* (2021) [ [38] ]
Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS/MS analysis. medRxiv. 2021; https://doi.org/10.1101/2021.06.02.21258097 | Sweden | 48/40 | UHPLC-MS | Nasopharyngeal swab | Virus nucleocapsid proteins |
Renuse (2021) [ [39] ] | India/USA | 204/159 | FAIMS-PRM | Nasopharyngeal swab | Virus nucleocapsid proteins |
Singh (2020) [ [40] ] | India | 83/20 | nLC-MS | Nasopharyngeal swab | Virus spike glycoprotein, replicase polyprotein |
3.2 Risk of bias and applicability of the tests reviewed
Bias | Applicability | ||||||
---|---|---|---|---|---|---|---|
Patient selection | Index test | Reference standard | Flow and timing | Patient selection | Index test | Reference standard | |
Berna (2021) | High | High | Low | Unclear | Low | Low | Low |
Cardozo (2020) | High | Low | Low | Low | Unclear | Low | Low |
Chivte (2021) | High | High | Low | Unclear | Unclear | Low | Low |
Delafiore (2020) | Low | Low | Low | Unclear | Low | Low | Low |
Delafiore (2021) | High | High | Low | Unclear | Low | Low | Low |
Deulofeu (2021) | Unclear | Low | Low | Low | Unclear | Low | Low |
Fraser (2020) | Low | High | Low | Unclear | Low | Low | Low |
Frampas (2021) | Low | High | Low | Low | Low | Low | Low |
Garza (2021) | High | High | Low | Low | Low | Low | Low |
Gray (2021) | High | Low | Low | Unclear | Low | Low | Low |
Grassin-Delyle (2020) | High | High | Low | Unclear | Low | Low | Low |
Hober (2021) | High | High | Low | Low | Unclear | Low | Low |
Kimhofer (2020) | High | High | Low | Unclear | Unclear | Low | Unclear |
Maras (2021) | High | Low | Low | Unclear | Low | Low | Low |
Nachtigall (2020) | Unclear | Low | Low | Low | Unclear | Low | Low |
Renuse (2021) | Unclear | Low | Low | Low | Unclear | Low | Low |
Rocca (2020) | Unclear | Low | Low | Low | Unclear | Low | Low |
Ruszkiewicz (2021) | High | High | Low | High | Low | Low | High |
Singh (2020) | High | Low | Low | Unclear | Unclear | Low | Low |
Spick (2021) | High | High | Low | Unclear | Low | Low | Low |
Tran (2021) | Low | Low | Low | Low | Unclear | Low | Low |
Wadah (2021) | Unclear | High | Low | Unclear | Low | Low | Low |
Yan (2020) | Low | Low | Low | Unclear | Low | Low | Low |

3.3 Diagnostic results of the studies
Study | Method | n employed in diagnostic model | Sensitivity (95% CI) | Specificity (95% CI) | Likelihood ratio (pos/neg) |
---|---|---|---|---|---|
Host-targeted approaches | |||||
Maras (2021) [ [20] ] | Proteomics - Host | 200 | 0.87 (0.79, 0.93) | 0.88 (0.80, 0.94) | 7.2/0.2 |
Rocca (2021) [ [21] ]
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. J Virol Methods. 2020; 286https://doi.org/10.1016/j.jviromet.2020.113991 | Proteomics – Host | 144 | 0.62 (0.49, 0.73) | 0.72 (0.62, 0.80) | 2.2/0.5 |
Yan (2021) [ [35] ] | Proteomics – Host | 100 | 0.98 (0.89, 1.00) | 1.00 (0.93, 1.00) | NA/0.02 |
Garza (2021) [ [22] ]
Rapid screening of COVID-19 directly from clinical nasopharyngeal swabs using the MasSpec Pen. Anal Chem. 2021; (published online Aug 25)https://doi.org/10.1021/acs.analchem.1c01937 | Lipidomics - Host | 171 | 0.82 (0.67, 0.92) | 0.77 (0.69, 0.84) | 3.6/0.2 |
Berna (2021) | Breathomics – Host | 24 | 0.91 (0.62, 1.00) | 0.75 (0.43, 0.95) | 3.7/0.1 |
Ruszkiewicz (2021) [ [23] ]
Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study. EClinicalMedicine. 2020; https://doi.org/10.1016/j.eclinm.2020.100609 | Breathomics – Host | 98 | 0.84 (0.66, 0.95) | 0.79 (0.67, 0.88) | 4.0/0.2 |
Wadah (2021) [ [24] ] | Breathomics – Host | 81 | 0.68 (0.53, 0.80) | 0.85 (0.68, 0.96) | 4.9/0.4 |
Grassin-Delyle (2020) [ [25] ] | Breathomics – Host | 28 | 0.90 (0.65, 0.99) | 0.94 (0.62, 1.00) | 10.7/0.1 |
Fraser (2020) [ [18] ] | Metabolomics – Host | 20 | 0.80 c (0.44, 0.97) | 1.00 c (0.69, 1.00) | NA/0.2 |
Delafiori (2021) [ [26] ] | Metabolomics – Host | 281 | 0.83 (0.78, 0.88) | 0.96 (0.86, 1.00) | 20.8/5.3 |
Kimhofer (2020) [ [27] ] | Multi-omics – Host | 18 | 1.00 (0.72, 1.00) | 1.00 (0.59, 1.00) | NA/0.0 |
Gray (2021) [ [28] ]
Diagnostic potential of the plasma lipidome in infectious disease: application to acute sars-cov-2 infection. Metabolites. 2021; 11https://doi.org/10.3390/metabo11070467 | Lipidomics - Host | 206 | 0.95 (0.90, 0.98) | 0.92 (0.81, 0.98) | 12.1/0.1 |
Spick (2021) [ [29] ] | Skin Lipidomics – Host | 67 | 0.79 (0.70, 0.87) | 0.83 (0.74, 0.90) | 4.7/0.3 |
Delafiori* (2021) [ [30] ] | Skin Lipidomics – Host | 101 | 0.74 (0.61, 0.84) | 0.82 (0.65, 0.92) | 3.9/0.3 |
Frampas* (2021) [ [31] ]
Untargeted saliva metabolomics reveals COVID-19 severity. medRxiv. 2021; https://doi.org/10.1101/2021.07.06.21260080 | Saliva Metabolomics | 75 | 0.77 (0.62, 0.88) | 0.75 (0.55, 0.89) | 3.1/0.3 |
Untargeted approaches | |||||
Deulofeu (2021) [ [34] ] | Untargeted – Host/Virus | 84 | 1.00 (0.92, 1.00) | 0.92 (0.79, 0.98) | 13.0/0.0 |
Nachtigall (2020) [ [33] ] | Untargeted – Host/Virus | 362 | 0.95 (0.91, 0.97) | 0.93 (0.87, 0.96) | 13.0/0.1 |
Tran (2021) [ [32] ] | Untargeted – Host/Virus | 117 | 1.00 (0.95, 1.00) | 0.96 (0.86, 1.00) | 25.0/0.0 |
Virus-targeted approaches | |||||
Cardozo (2020) [ [36] ] | Proteomics – Virus | 108 | 0.84 (0.71, 0.92) | 0.93 (0.83, 0.99) | 13.3/0.2 |
Chivte (2021) [ [37] ]
MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19. J Mass Spectrom Adv Clin Lab. 2021; https://doi.org/10.1016/j.jmsacl.2021.09.001 | Proteomics/Virus | 60 | 1.00 (0.88, 1.00) | 0.93 (0.78, 0.99) | 15.0/0.0 |
Hober* (2021) [ [38] ]
Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS/MS analysis. medRxiv. 2021; https://doi.org/10.1101/2021.06.02.21258097 | Proteomics/Virus | 88 | 0.83 (0.70, 0.93) | 1.00 (0.91, 1.00) | NA/0.2 |
Renuse (2021) [ [39] ] | Proteomics/Virus | 176 | 0.98 (0.92, 1.00) | 1.00 (0.96, 1.00) | NA/0.0 |
Singh (2020) [ [40] ] | Proteomics - Virus | 83 | 0.90 (0.80, 0.96) | 1.00 (0.83, 1.00) | NA/0.1 |

3.4 Heterogeneity assessment of the studies
- Rücker G.
- Schwarzer G.
- Carpenter J.R.
- Schumacher M.

4. Discussion
- Pang Z.
- Zhou G.
- Chong J.
- Xia J.
- Lisboa Bastos M.
- Tavaziva G.
- Abidi S.K.
- et al.
- Frampas C.
- Longman K.
- Spick M.
- et al.
- Gutmann C.
- Takov K.
- Burnap S.A.
- et al.
- Eyre M.T.
- Burns R.
- Kirkby V.
- et al.
- Zipfel C.M.
- Colizza V.
- Bansal S.
5. Conclusions
Funding
CRediT authorship contribution statement
Declaration of competing interest
Appendix A. Supplementary data
Supplementary material
References
- WHO Coronavirus Disease (COVID-19) Dashboard.https://covid19.who.int/(accessed Sept 17, 2020)Date: 2020
- Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19.Am J Infect Control. 2021; 49: 21-29
- COVID-19 diagnosis — a review of current methods.Biosens Bioelectron. 2021; 172https://doi.org/10.1016/j.bios.2020.112752
- Metabolomics by numbers: acquiring and understanding global metabolite data.Trends Biotechnol. 2004; 22: 245-252
- Mass spectrometry-based ‘omics’ technologies in cancer diagnostics.Mass Spectrom Rev. 2007; 26: 403-431
- Mass spectrometry analytical responses to the SARS-CoV2 coronavirus in review.TrAC Trends Anal Chem. 2021; : 116328
- Guidance for industry and manufacturers: COVID-19 tests and testing kits.(accessed June 17, 2021)
- SARS-COV-2 DIAGNOSTIC USE CASES.https://www.finddx.org/dx-use-cases/(accessed June 17, 2021)Date: 2021
- Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement.JAMA. 2018; 319: 388-396
- QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.Ann Intern Med. 2011; 155: 529-536
- The combination of estimates from different experiments.Biometrics. 1954; 10: 101
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- R: A Language and Environment for Statistical Computing.https://www.r-project.org/Date: 2020
- RStudio: Integrated development environment for R.http://www.rstudio.com/Date: 2020
Mark Stevenson with contributions from Telmo Nunes and Cord Heuer and Jonathon Marshall and Javier Sanchez and Ron Thornton and Jeno Reiczigel and Jim Robison-Cox and Paola Sebastiani and Peter Solymos and Kazuki Yoshida and Geoff Jones and Sarah Pirikahu. epiR: Tools for the Analysis of Epidemiological Data. 2017. https://cran.r-project.org/package=epiR (accessed May 14, 2021).
- forestplot: advanced forest plot using ‘grid’ graphics. r packagage version 1.10.1.
- Stat. Appl. to Clin. Trials.2008: 415-421
- Metabolomics profiling of critically ill coronavirus disease 2019 patients: identification of diagnostic and prognostic biomarkers.Crit Care Explor. 2020; 2e0272
- Epidemic Intelligence from Open Sources (EIOS).(accessed June 3, 2021)
- Multi-omics analysis of respiratory specimen characterizes baseline molecular determinants associated with SARS-CoV-2 outcome.iScience. 2021; 24: 102823
- 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.J Virol Methods. 2020; 286https://doi.org/10.1016/j.jviromet.2020.113991
- Rapid screening of COVID-19 directly from clinical nasopharyngeal swabs using the MasSpec Pen.Anal Chem. 2021; (published online Aug 25)https://doi.org/10.1021/acs.analchem.1c01937
- Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study.EClinicalMedicine. 2020; https://doi.org/10.1016/j.eclinm.2020.100609
- Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography–mass spectrometry.ERJ Open Res. 2021; 7: 139-2021https://doi.org/10.1183/23120541.00139-2021
- Metabolomics of exhaled breath in critically ill COVID-19 patients: a pilot study.EBioMedicine. 2021; 63 (0–6)
- Covid-19 automated diagnosis and risk assessment through metabolomics and machine learning.Anal Chem. 2021; 93: 2471-2479
- Integrative modeling of quantitative plasma lipoprotein, metabolic, and amino acid data reveals a multiorgan pathological signature of SARS-CoV-2 infection.J Proteome Res. 2020; 19: 4442-4454
- Diagnostic potential of the plasma lipidome in infectious disease: application to acute sars-cov-2 infection.Metabolites. 2021; 11https://doi.org/10.3390/metabo11070467
- Changes to the sebum lipidome upon COVID-19 infection observed via rapid sampling from the skin.EClinicalMedicine. 2021; : 100786
- Skin imprints to provide noninvasive metabolic profiling of COVID-19 patients.2021: 1-17
- Untargeted saliva metabolomics reveals COVID-19 severity.medRxiv. 2021; https://doi.org/10.1101/2021.07.06.21260080
- Novel application of automated machine learning with MALDI-TOF-MS for rapid high-throughput screening of COVID-19: a proof of concept.Sci Rep. 2021; 11: 1-10
- Detection of SARS-CoV-2 in nasal swabs using MALDI-MS.Nat Biotechnol. 2020; 38: 1168-1173
- Detection of SARS-CoV-2 infection in human nasopharyngeal samples by combining MALDI-TOF MS and artificial intelligence.Front Med. 2021; 8: 1-12
- Rapid detection of COVID-19 using MALDI-TOF-based serum peptidome profiling.Anal Chem. 2021; 93: 4782-4787
- Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts.Nat Commun. 2020; 11: 1-13
- MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19.J Mass Spectrom Adv Clin Lab. 2021; https://doi.org/10.1016/j.jmsacl.2021.09.001
- Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS/MS analysis.medRxiv. 2021; https://doi.org/10.1101/2021.06.02.21258097
- A mass spectrometry-based targeted assay for detection of SARS-CoV-2 antigen from clinical specimens.EBioMedicine. 2021; 69: 103465
- A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry.J Proteins Proteomics. 2020; 11: 159-165
- Cautionary tales in the clinical interpretation of studies of diagnostic tests.Intern Med J. 2008; 38: 120-129
- Undue reliance on I2 in assessing heterogeneity may mislead.BMC Med Res Methodol. 2008; 8https://doi.org/10.1186/1471-2288-8-79
- Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection.Cell Syst. 2020; 1111-24.e4
- Article proteomic and metabolomic characterization of COVID-19 patient Sera ll article proteomic and metabolomic characterization of COVID-19 Patient Sera.2020: 59-72
- A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies.J Proteins Proteomics. 2020; : 1-10
- Comprehensive meta-analysis of COVID-19 global metabolomics datasets.Metabolites. 2021; 11https://doi.org/10.3390/metabo11010044
- Criteria for releasing COVID-19 patients from isolation.https://www.who.int/publications/i/item/criteria-for-releasing-covid-19-patients-from-isolation(accessed June 17, 2021)Date: 2021
- Patient safety recommendations and management in patients with COVID-19 pneumonia suspicion: a retrospective study.Clin Ter. 2021; 172: 225-230
- Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.BMJ. 2020; 370https://doi.org/10.1136/bmj.m2516
- Chest CT versus RT-PCR for the detection of COVID-19: systematic review and meta-analysis of comparative studies.JRSM Open. 2021; 12 (205427042110118)
- ACR recommendations for the use of chest radiography and Computed Tomography (CT) for suspected COVID-19 infection.(accessed July 29, 2021)
- The serum metabolome of COVID-19 patients is distinctive and predictive.Metabolism. 2021; 118: 154739
- SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.Nat Commun. 2021; 12https://doi.org/10.1038/s41467-021-23494-1
- COVID-19 Target product profiles for priority diagnostics to support response to the COVID-19 pandemic v.1.0.2020: 1-38
- Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study [version 2; peer review: 2 approved].Wellcome Open Res. 2021; 5https://doi.org/10.12688/wellcomeopenres.16304.2
- The missing season: the impacts of the COVID-19 pandemic on influenza.Vaccine. 2021; https://doi.org/10.1016/j.vaccine.2021.05.049
- Anticipating outcomes for patients with COVID-19 and identifying prognosis patterns.Lancet Infect Dis. 2021; 21: 744-745
Article info
Publication history
Identification
Copyright
User license
Creative Commons Attribution (CC BY 4.0) |
Permitted
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
Elsevier's open access license policy