ATR-FTIR spectrum analysis of saliva samples from COVID-19 positive patients

Martínez-Cuazitl, Adriana; Vázquez-Zapién, Gustavo Jesús; Sánchez-Brito, Miguel; Limón-Pacheco, Jorge H.; Guerrero-Ruiz, Melissa; Garibay-Gonzalez, Francisco; Delgado-Macuil, R.; Jesus, Maria G. Garcia de; Corona-Perezgrovas, Miguel A.; Pereyra-Talamantes, Armando; Mata-Miranda, Mónica Maribel

doi:10.1038/s41598-021-99529-w

Cited by 55 publications

(64 citation statements)

References 53 publications

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“…In addition, seven points of varying significance (p < 0.06-0.01) correlated with the significant peaks from the COVID.POS FU.POS vs. COVID.NEG comparison: right shift of amide I (1688/1658 cm −1 ); decreased aliphatic/RNA (1430 cm −1 ); decreased δCH 3 − bending (1373 cm −1 ); decreased ν s PO 2 − RNA (1124 cm −1 ), ν s PO 2 − , symmetric, and C-O ν ribose (1071 cm −1 ); decreased νC 4 -OH − glucose (1016 cm −1 ). The right shifting amide I peak in COVID.POS FU.POS , compared to both COVID.NEG and COVID.POS FU.NEG , is in agreement with residual misfolded amyloid protein fibrils and elevated IgA in COVID-19 patient saliva (Figure S5) [9,26,27].…”

Section: Comparison Of Covid-19 Spectral Signature Across Diverse Modelssupporting

confidence: 71%

“…As an alternative to using specific reagents (i.e., PCR primers, antibodies) to detect SARS-CoV-2 viral RNA or proteins, Fourier transform infrared (FTIR) spectroscopy was recently reported as a promising, point-of-care technology for COVID-19 detection using a pharyngeal swab or saliva [ 8 , 9 , 10 ]. FTIR provides a biochemical snapshot of the sample by measuring the vibration states of chemical bonds [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…FTIR provides a biochemical snapshot of the sample by measuring the vibration states of chemical bonds [ 11 ]. FTIR spectra collected from the saliva of COVID-19 patients and healthy controls have been used to develop prediction algorithms that demonstrate high predictive accuracy in the cross-validation of the same cohort [ 9 , 10 ] or in an independent cohort [ 8 ]. FTIR sampling, using either transflection (slide mount) or attenuated total reflectance (ATR, directly deposited onto highly reflective crystal), was able to distinguish healthy controls from confirmed COVID-19 cases with high specificity and sensitivity [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19

et al. 2022

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Fourier transform infrared (FTIR) spectroscopy provides a (bio)chemical snapshot of the sample, and was recently used in proof-of-concept cohort studies for COVID-19 saliva screening. However, the biological basis of the proposed technology has not been established. To investigate underlying pathophysiology, we conducted controlled infection experiments on Vero E6 cells in vitro and K18-hACE2 mice in vivo. Potentially infectious culture supernatant or mouse oral lavage samples were treated with ethanol or 75% (v/v) Trizol for attenuated total reflectance (ATR)-FTIR spectroscopy and proteomics, or RT-PCR, respectively. Controlled infection with UV-inactivated SARS-CoV-2 elicited strong biochemical changes in culture supernatant/oral lavage despite a lack of viral replication, determined by RT-PCR or a cell culture infectious dose 50% assay. Nevertheless, SARS-CoV-2 infection induced additional FTIR signals over UV-inactivated SARS-CoV-2 infection in both cell and mouse models, which correspond to aggregated proteins and RNA. Proteomics of mouse oral lavage revealed increased secretion of kallikreins and immune modulatory proteins. Next, we collected saliva from a cohort of human participants (n = 104) and developed a predictive model for COVID-19 using partial least squares discriminant analysis. While high sensitivity of 93.48% was achieved through leave-one-out cross-validation, COVID-19 patients testing negative on follow-up on the day of saliva sampling using RT-PCR was poorly predicted in this model. Importantly, COVID-19 vaccination did not lead to the misclassification of COVID-19 negatives. Finally, meta-analysis revealed that SARS-CoV-2 induced increases in the amide II band in all arms of this study and in recently published cohort studies, indicative of altered β-sheet structures in secreted proteins. In conclusion, this study reveals a consistent secretory pathophysiological response to SARS-CoV-2, as well as a simple, robust method for COVID-19 saliva screening using ATR-FTIR.

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Section: Comparison Of Covid-19 Spectral Signature Across Diverse Modelssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19

et al. 2022

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“…These results are in concordance with other studies describing higher serum ferritin concentration in patients with severe manifestations [ 36 , 37 , 38 ] in comparison with less severe patients, with increases ranging from 1.5- to 5.3-fold [ 6 ]. Blood ferritin, together with other biomarkers such as C-reactive protein or D-dimer have been proposed to be used in risk stratification to predict severe and fatal COVID-19 in hospitalized patients [ 19 , 39 ]. This could be because serum ferritin shows major increases in severe inflammation and autoimmune response [ 9 , 13 , 14 ], processes that can be present in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Salivary Ferritin Changes in Patients with COVID-19

Franco‐Martínez

Cerón

Vicente-Romero

et al. 2021

IJERPH

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High ferritin serum levels can be found in patients with macrophage activation syndrome, and increased serum ferritin due to cytokine storm have been reported in severe COVID-19 patients. Saliva is being increasingly used in COVID-19 tests as a diagnostic sample for virus detection and quantification. This study aimed to evaluate the possible changes in ferritin in saliva in COVID-19 patients. In addition, the effects of different inactivation SARS-CoV-2 treatments in ferritin measurements in saliva, the correlation between ferritin in saliva and serum, and the possible effects of correction of ferritin values by total protein were assessed. Ferritin was measured in saliva from healthy (n = 30) and COVID-19 (n = 65) patients with severe, (n = 18) or mild (n = 47) disease, depending on the need for nasal flow oxygen or assisted respiration. Ferritin was also measured in paired serum and saliva samples (n = 32) from healthy and COVID-19 patients. The evaluated inactivation protocols did not affect the assay’s results except the addition of 0.5% SDS. Significantly higher ferritin was found in the saliva of COVID-19 patients (median; 25–75th percentile) (27.75; 9.77–52.2 µg/L), compared with healthy controls (4.21; 2.6–8.08 µg/L). Individuals with severe COVID-19 showed higher ferritin values in saliva (48.7; 18.7–53.9) than mild ones (15.5; 5.28–41.3 µg/L). Significant correlation (r = 0.425; p < 0.001) was found between serum and saliva in ferritin. Ferritin levels were higher in COVID-19 patients in serum and saliva, and the highest values were found in those patients presenting severe symptomatology. In conclusion, ferritin in saliva has the potential to be a biomarker to evaluate severity in patients with COVID-19.

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“…Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy has emerged as a powerful tool in the medical diagnostic field [36,37]. ATR-FTIR has been extensively explored to identify molecular vibrations of biomolecules in various biological samples that are useful for monitoring health status [38,39]. Some advantages provided by ATR-FTIR include the ease of handling samples with relatively short measurement duration (only a few minutes), a small amount of required sample volume, a reagent-free approach, and high signal to noise ratio output that facilitates chemometric analysis.…”

Section: Introductionmentioning

confidence: 99%

Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Discriminates the Elderly with a Low and High Percentage of Pathogenic CD4+ T Cells

Praja

Wongwattanakul

Tippayawat

et al. 2022

Cells

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In the aging process, the presence of interleukin (IL)-17-producing CD4+CD28-NKG2D+T cells (called pathogenic CD4+ T cells) is strongly associated with inflammation and the development of various diseases. Thus, their presence needs to be monitored. The emergence of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy empowered with machine learning is a breakthrough in the field of medical diagnostics. This study aimed to discriminate between the elderly with a low percentage (LP; ≤3%) and a high percentage (HP; ≥6%) of pathogenic CD4+CD28-NKG2D+IL17+ T cells by utilizing ATR-FTIR coupled with machine learning algorithms. ATR spectra of serum, exosome, and HDL from both groups were explored in this study. Only exosome spectra in the 1700–1500 cm−1 region exhibited possible discrimination for the LP and HP groups based on principal component analysis (PCA). Furthermore, partial least square-discriminant analysis (PLS-DA) could differentiate both groups using the 1700–1500 cm−1 region of exosome ATR spectra with 64% accuracy, 69% sensitivity, and 61% specificity. To obtain better classification performance, several spectral models were then established using advanced machine learning algorithms, including J48 decision tree, support vector machine (SVM), random forest (RF), and neural network (NN). Herein, NN was considered to be the best model with an accuracy of 100%, sensitivity of 100%, and specificity of 100% using serum spectra in the region of 1800–900 cm−1. Exosome spectra in the 1700–1500 and combined 3000–2800 and 1800–900 cm−1 regions using the NN algorithm gave the same accuracy performance of 95% with a variation in sensitivity and specificity. HDL spectra with the NN algorithm also showed excellent test performance in the 1800–900 cm−1 region with 97% accuracy, 100% sensitivity, and 95% specificity. This study demonstrates that ATR-FTIR coupled with machine learning algorithms can be used to study immunosenescence. Furthermore, this approach can possibly be applied to monitor the presence of pathogenic CD4+ T cells in the elderly. Due to the limited number of samples used in this study, it is necessary to conduct a large-scale study to obtain more robust classification models and to assess the true clinical diagnostic performance.

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ATR-FTIR spectrum analysis of saliva samples from COVID-19 positive patients

Cited by 55 publications

References 53 publications

Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19

Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19

Salivary Ferritin Changes in Patients with COVID-19

Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Discriminates the Elderly with a Low and High Percentage of Pathogenic CD4+ T Cells

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