Superiority of MALDI-TOF Mass Spectrometry over Real-Time PCR for SARS-CoV-2 RNA Detection

Abstract

At present, the RT-PCR test remains the gold standard for early diagnosis of SARS-CoV-2. Nevertheless, there is growing evidence demonstrating that this technique may generate false-negative results. Here, we aimed to compare the new mass spectrometry-based assay MassARRAY® SARS-CoV-2 Panel with the RT-PCR diagnostic test approved for clinical use. The study group consisted of 168 suspected patients with symptoms of a respiratory infection. After simultaneous analysis by RT-PCR and mass spectrometry methods, we obtained discordant results for 17 samples (10.12%). Within fifteen samples officially reported as presumptive positive, 13 were positive according to the MS-based assay. Moreover, four samples reported by the officially approved RT-PCR as negative were positive in at least one MS assay. We have successfully demonstrated superior sensitivity of the MS-based assay in SARS-CoV-2 detection, showing that MALDI-TOF MS seems to be ideal for the detection as well as discrimination of mutations within the viral genome.

Application and Perspectives of MALDI–TOF Mass Spectrometry in Clinical Microbiology Laboratories

“…At present with the current COVID-19 pandemic, the need for a rapid diagnosis of SARS-CoV-2 has generated a rapid evolution and optimization of clinical methods, including MALDI–TOF MS. Because the gold standard and main diagnosis tool for SARS-CoV-2, the RT-PCR, is continuously producing false negatives, questions are being raised about whether MS-based technology, such as MassARRAY, which demonstrates superior sensitivity and discrimination of mutations within the viral genome, should overtake it [ 114 , 115 ]. MS-based methods using swab and saliva samples are reporting promising results.…”

Current diagnostic approaches to detect two important betacoronaviruses: Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

“…For SARS-CoV-2, a PCR test that was coupled with MS was also widely used to detect this coronavirus ( Table 8 ) [157] , [158] , [159] , [160] . In a Chinese study [159] , a PCR test coupled with an MS test was used to detect the N and ORF 1ab genes of SARS-CoV and the detection rate of this assay was noted to be around 75%.…”

“…The drawback of this study was that the tendency of the assay to cross-react with other pathogens was unexplored and thus, the test specificity was unclear [160] . The test specificity of the PCR-MS-based test was also unspecified in another study [158] , even though the study reported that such test could detect 400 RNA copies in 1 mL. To further compare the sensitivity and specificity of PCR-MS-based tests in detecting SARS-CoV-2 with other diagnostic methods, a study was conducted in Germany and it was shown that PCR-MS-based assay would produce test sensitivity and specificity that was comparable and concordance to qRT-PCR test findings [157] .…”

“Multiomics” Approaches to Understand and Treat COVID-19: Mass Spectrometry and Next-Generation Sequencing

“…Hence, there is a growing popularity of all the above high-throughput multiomics methods involving next-generation sequencing for a wellrounded understanding of COVID-19. MS-based methods have been employed in several clinical studies worldwide, some of which are summarized in Table 1, and have also been indicated to be a superior method for COVID-19 screening [41,42]. This review will, therefore, discuss both mass spectrometry and next generation sequencing-based approaches to interrogate COVID-19.…”