PREreview of Targeted proteomics as a tool to detect SARS-CoV-2 proteins in clinical specimens

Targeted proteomics as a tool to detect SARS-CoV-2 proteins in clinical specimens

by Karel Bezstarosti, Mart M. Lamers, Wouter A.S. Doff, Peter Wever, Khoa Thai, Jeroen J. A. van Kampen, Bart L. Haagmans, and Jeroen A. A. Demmers

In this study, Karel Bezstarosti et al tried to develop a diagnostic tool for the detection of SARS-CoV-2 infection using clinical specimens such as nasopharyngeal swabs, mucus, and sputum. This method is able to detect various viral peptide fragments with high sensitivity. There are a few points that I would like to highlight in this study:

1. This technique detects multiple peptide fragments of viral proteins, which makes it reliable in the case of mutation and evolution in strains. However, this requires constant updates of the protein database if a single peptide is used for diagnosis.

2. They have mentioned that further optimization is required with a larger sample size, but with the given samples, specifically cohort 1, that had SARS-CoV-2 positive samples, they could not detect viral peptides in all the samples. This indicates that even the current method needs further optimization.

3. The sample transport, neutralization (to get clearance from BSL 3), and processing for proteomics need to be further streamlined as different collection kits have introduced variability in the given study (cohort 2).

4. Considering the pandemic scenario, the sample size, and the heterogeneity of the samples, the reliability of this method will immediately raise questions.

5. Compared to the traditional RT-PCR based method, the results are inconsistent even with a small sample size. There were a considerable number of false negatives reported from the test samples.

6. The author has not provided sufficient explanation and strategies that could be used to improve this method.

7. There was no explanation in a case where the AQUA internal standard could not be detected despite having the same extraction protocol.

8. For the data presentation they could have plotted the AUC in log scale so that in case of low intensity signal the data visualisation could have been easier for the reader.

9. In the discussion section, paragraph 4, the point where it is mentioned that RNA could be present without the capsule protein and are present even after infection needs to be supported by literature, as we know proteins are generally more stable and tend to remain in the circulation for longer than single-stranded RNA.

In terms of logistics, this method seems to be less cost-efficient and the investment required to setup testing centers with such facilities is beyond scope for many third-world countries. Otherwise the method seems to have a promising prospect. It does provide avenues for covid related studies and for the study and detection of rare diseases in the population. These sorts of ideas do add a new dimension when we consider the trend in public health.

Competing interests

The author declares that they have no competing interests.