Urine Metabolites Enable Fast Detection of COVID-19 Using Mass Spectrometry

Abstract

The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection–tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines. We adapted a method that is widely used for newborn screening tests on dried blood for urine samples in order to detect metabolites related to COVID-19 infection. We analyzed samples from 246 volunteers with diagnostic confirmation via PCR. Urine samples were self-collected, diluted, and analyzed with a run time of 4 min. A Lasso statistical classifier was built using 75/25% data for training/validation sets and achieved high diagnostic performances: 97/90% sensitivity, 95/100% specificity, and 95/97.2% accuracy. Additionally, we predicted on two withheld sets composed of suspected hospitalized/symptomatic COVID-19-PCR negative patients and patients out of the optimal time-frame collection for PCR diagnosis, with promising results. Altogether, we show that the benchmarked FIA-MS/MS method is promising for COVID-19 screening and diagnosis, and is also potentially useful after the peak viral load has passed.

Urine Parameters in Patients with COVID-19 Infection

“…In addition, the simultaneous increase in combined PRO and haematuria correlated with mortality in COVID-19 patients [12]. for GLU [7,8,11]; for LEU (a) severe and critical COVID-19 [7,8,42], (b) COVID-19 AKI [25]; for KET [16]; for SG [4,5,10,16]; for BLOOD (a) severe and critical COVID-19 [7,8,10,11,29], (b) COVID-19 AKI [16,22,44], (c) COVID-19 mortality [14,16].…”

“…The incidence of these two parameters was not as high as in the previously mentioned studies; however, it can predict adverse renal outcomes in long-term follow-up since Omicron infections may cause new kidney involvement [45]. for GLU [7,8,11]; for LEU (a) severe and critical COVID-19 [7,8,42], (b) COVID-19 AKI [25]; for KET [16]; for SG [4,5,10,16]; for BLOOD (a) severe and critical COVID-19 [7,8,10,11,29], (b) COVID-19 AKI [16,22,44], (c) COVID-19 mortality [14,16].…”

Diagnostic, Prognostic and Mechanistic Biomarkers of COVID-19 Identified by Mass Spectrometric Metabolomics

“…Attempts have been launched to complement standard microbiological and biochemical methods of infection diagnosis by metabolomic analyses to guide specific and tailored antimicrobial therapies for critically ill COVID-19 patients [ 84 ]. In addition, urine-based diagnostic tests have been proposed as “comfortable” by Moura et al to increase the adherence of individuals to routine testing [ 85 ]. The authors developed a rapid procedure based on multiplex flow injection analysis using tandem mass spectrometry (FIA-MS/MS).…”

Data Acquisition and Intraoperative Tissue Analysis on a Mobile, Battery-Operated, Orbitrap Mass Spectrometer

“…Mass spectrometry (MS) is particularly well suited for the analysis of complex biological samples due to the high chemical specificity and sensitivity achieved with high-performance MS instrumentation. Direct MS analysis of human tissues can result in rich molecular profiles comprised of hundreds to thousands of m / z values corresponding to metabolites, lipids, and proteins, which carry clinical and diagnostic value. − Yet, despite the success of MS technologies in analyzing clinical samples in academic and industrial institutions, implementation of MS within hospitals has been largely limited to research and clinical laboratories and is still a growing field of research.…”