We have developed a rapid and highly specific assay for detecting and monitoring SARS-CoV-2 infections by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). As MALDI-TOF mass spectrometers are available in a clinical setting, our assay has the potential to serve as alternative to the commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Sample preparation prior to MALDI-TOF-MS involves the tryptic digestion of SARS-CoV-2 proteins, followed by an enrichment of virus-specific peptides from SARS-CoV-2 nucleoprotein via magnetic antibody beads. Our MALDI-TOF-MS method allows the detection of SARS-CoV-2 nucleoprotein in sample collection medium as low as 8 amol/µl. MALDI-TOF mass spectra are obtained in just a few seconds, which makes our MS-based assay suitable for a high-throughput screening of SARS-CoV-2 in healthcare facilities in addition to PCR. Due to the specific detection of virus peptides, different SARS-CoV-2 variants are readily distinguished from each other. Specifically, we show that our MALDI-TOF-MS assay discriminates SARS-CoV-2 strain B.1.617.2 “delta variant” from all other variants in patients’ samples, making our method highly valuable to monitor the emergence of new virus variants.

中文翻译：

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开发用于 SARS-CoV-2 检测的快速特异性 MALDI-TOF 质谱分析方法

我们开发了一种快速、高度特异性的检测方法，通过基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF-MS) 来检测和监测 SARS-CoV-2 感染。由于 MALDI-TOF 质谱仪可用于临床环境，因此我们的检测有可能替代常用的逆转录酶定量聚合酶链反应 (RT-qPCR)。MALDI-TOF-MS 之前的样品制备涉及 SARS-CoV-2 蛋白的胰蛋白酶消化，然后通过磁性抗体珠从 SARS-CoV-2 核蛋白中富集病毒特异性肽。我们的 MALDI-TOF-MS 方法可以检测样品收集介质中低至 8 amol/μl 的 SARS-CoV-2 核蛋白。MALDI-TOF 质谱只需几秒钟即可获得，这使得我们基于 MS 的检测除 PCR 之外还适用于医疗机构中 SARS-CoV-2 的高通量筛查。由于病毒肽的特异性检测，不同的 SARS-CoV-2 变体很容易彼此区分。具体来说，我们表明我们的 MALDI-TOF-MS 检测可将 SARS-CoV-2 病毒株 B.1.617.2“δ 变体”与患者样本中的所有其他变体区分开来，这使得我们的方法对于监测新病毒变体的出现非常有价值。