MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19

Prajkta Chivte; Zane LaCasse; Venkata Devesh R Seethi; Pratool Bharti; Joshua Bland; Shrihari S Kadkol; Elizabeth R Gaillard

doi:10.1016/j.jmsacl.2021.09.001

MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19

J Mass Spectrom Adv Clin Lab. 2021 Aug:21:31-41. doi: 10.1016/j.jmsacl.2021.09.001. Epub 2021 Sep 9.

Authors

Prajkta Chivte¹, Zane LaCasse¹, Venkata Devesh R Seethi², Pratool Bharti², Joshua Bland³, Shrihari S Kadkol³, Elizabeth R Gaillard¹

Affiliations

¹ Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, United States.
² Department of Computer Science, Northern Illinois University, DeKalb, IL 60115, United States.
³ Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, United States.

Abstract

More than a year after the COVID-19 pandemic was declared, the need still exists for accurate, rapid, inexpensive and non-invasive diagnostic methods that yield high specificity and sensitivity towards the current and newly emerging SARS-CoV-2 strains. Compared to the nasopharyngeal swabs, several studies have established saliva as a more amenable specimen type for early detection of SARS-CoV-2. Considering the limitations and high demand for COVID-19 testing, we employed MALDI-ToF mass spectrometry in the analysis of 60 gargle samples from human donors and compared the resultant spectra against COVID-19 status. Several standards, including isolated human serum immunoglobulins, and controls, such as pre-COVID-19 saliva and heat inactivated SARS-CoV-2 virus, were simultaneously analyzed to provide a relative view of the saliva and viral proteome as they would appear in this workflow. Five potential biomarker peaks were established that demonstrated high concordance with COVID-19 positive individuals. Overall, the agreement of these results with RT-qPCR testing on nasopharyngeal swabs was ≥90% for the studied cohort, which consisted of young and largely asymptomatic student athletes. From a clinical standpoint, the results from this pilot study suggest that MALDI-ToF could be used to develop a relatively rapid and inexpensive COVID-19 assay.

Keywords: ACE2, angiotensin-converting enzyme 2; AUC, area under the curve; Asymptomatic; COVID-19 testing; COVID-19, coronavirus disease 2019; Ct, cycle threshold, DTT, dithiothreitol; E Protein, envelope protein; EUA, emergency use authorization; FDA, food and drug administration; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; Immunoglobulins; LoD, limit of detection, LC-MS, liquid chromatography mass spectrometry; M Protein, membrane protein; MALDI-ToF; MALDI-ToF MS, matrix-assisted laser desorption/ionization-time of flight mass spectrometry; N Protein, nucleocapsid protein; NP, nasopharyngeal; RBD, receptor binding domain; RNA, ribonucleic acid; ROC, receiver operating characteristic, RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; S Protein, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Saliva; VEP, viral envelope protein; WHO, world health organization.