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Article

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

1
Precision & Systems Biomedicine Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
2
Biostatistics Unit, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
3
Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
4
New South Wales Health Pathology-Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
5
Agilent Technologies Australia, Mulgrave, VIC 3170, Australia
6
Lung Inflammation & Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
7
The Prince Charles Hospital, Chermside, QLD 4032, Australia
8
Australian Infectious Disease Research Centre, GVN Centre of Excellence, Brisbane, QLD 4029, Australia
9
UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD 4006, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Santiago Garcia-Vallve
Biomedicines 2022, 10(2), 351; https://doi.org/10.3390/biomedicines10020351
Received: 30 December 2021 / Revised: 10 January 2022 / Accepted: 26 January 2022 / Published: 1 February 2022
(This article belongs to the Special Issue Feature Papers in Molecular and Translation Medicine)
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. View Full-Text
Keywords: fourier transform infrared spectroscopy; FTIR; COVID-19 pandemic; kallikrein fourier transform infrared spectroscopy; FTIR; COVID-19 pandemic; kallikrein
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MDPI and ACS Style

Kazmer, S.T.; Hartel, G.; Robinson, H.; Richards, R.S.; Yan, K.; van Hal, S.J.; Chan, R.; Hind, A.; Bradley, D.; Zieschang, F.; Rawle, D.J.; Le, T.T.; Reid, D.W.; Suhrbier, A.; Hill, M.M. Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19. Biomedicines 2022, 10, 351. https://doi.org/10.3390/biomedicines10020351

AMA Style

Kazmer ST, Hartel G, Robinson H, Richards RS, Yan K, van Hal SJ, Chan R, Hind A, Bradley D, Zieschang F, Rawle DJ, Le TT, Reid DW, Suhrbier A, Hill MM. Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19. Biomedicines. 2022; 10(2):351. https://doi.org/10.3390/biomedicines10020351

Chicago/Turabian Style

Kazmer, Seth T., Gunter Hartel, Harley Robinson, Renee S. Richards, Kexin Yan, Sebastiaan J. van Hal, Raymond Chan, Andrew Hind, David Bradley, Fabian Zieschang, Daniel J. Rawle, Thuy T. Le, David W. Reid, Andreas Suhrbier, and Michelle M. Hill. 2022. "Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19" Biomedicines 10, no. 2: 351. https://doi.org/10.3390/biomedicines10020351

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