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COVID-19: using mass spectrometry to diagnose and assess viral load

​A CEA-Joliot team is developing with the AP-HP a mass spectrometry diagnostic test for COVID-19 that would also make it possible to assess the patient's viral load. Their aim is to make the method more sensitive and more compatible with hospital equipment.

Published on 12 April 2021

Several teams from the CEA-Joliot's Pharmacology and Immunoanalysis unit are working on the development of new diagnostic tests for COVID-19: on the one hand are rapid immunological, antigenic or serological tests, and on the other hand, mass spectrometry tests. The latter could eventually be used in hospitals and analysis laboratories, in addition to the reference PCR test.

Indeed, mass spectrometry allows detecting proteins in a manner complementary to PCR, which can be used to analyze the genome. The reagents for mass spectrometry are common and inexpensive, and analysis laboratories, especially those in hospitals, are equipped with the necessary equipment. Finally, some protocols are quantitative, which would therefore make it possible to assess the viral load.

In collaboration with the bacteriology unit at the Hôpital Bicêtre (AP-HP), researchers at the CEA-Joliot capitalized on the ability of mass spectrometry to detect coronavirus proteins in order to develop an analytical protocol. This protocol, which can be applied in hospitals, does not require any specific reagent and can be used to assess the quantity of the three main constituent proteins of the SARS-CoV-2 virus: the Nucleoprotein N, Spike S, and Membrane M proteins. The simultaneous detection of these three proteins, as opposed to one in most cases, gives this test a particular advantage.

Nasopharyngeal samples were collected from COVID patients and tested by three different methods to compare, for the first time, their respective performances: first by PCR, then by immunoanalysis (antigenic tests), and finally with the analytical protocol developed by the CEA-Joliot researchers. To ensure an accurate evaluation, the new protocol was tested first in various media used to preserve the virus before PCR analysis, which could be unsuitable for mass spectrometry analysis because of their high protein content.

The new methodology was able to reach a lower detection limit of 2,000 viral particles/mL from the nasopharyngeal samples, without any significant impact from the different collection and storage media in common use that were evaluated during the study. Furthermore, by confirming 75% of positive samples by PCR, this method proved to be more sensitive than other methods also based on mass spectrometry. The CEA-Joliot researchers are now pursuing this work to improve the sensitivity of the approach and adapt it to MALDI-TOF instruments, which are available in the vast majority of clinical microbiology laboratories.

This work provides important diagnostic perspectives that complement existing tests, regarding viral load quantification and the detection of new variants of SARS-Cov-2.

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