RR:C19 Evidence Scale rating by reviewer:
Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.
1. Yousefi et al. report the use of an electrodetethered sensor that is coated with spike protein-specific antibody linked to a negatively charged DNA linker for detection of Coronavirus particles for amperometry measurement of signal. The authors claim that the results can be obtained in 5 min. The approach is novel and the proof-of-concept data show great potential for the success of such a sensor; however, interferences from sample matrices must be thoroughly examined to overcome potential false-results.
2. The authors claim it is a reagent-free assay which is highly misleading since antibodies and the DNA linkers are part of reagents that are used for analyte detection. It is unclear what the authors meant by reagent-free. An assay cannot be performed without any of those reagents and buffers. Revision should be made throughout the article including the title.
3. Based on the results presented in Fig 3c, the earliest time one can begin to observe a positive signal with SARS-COV-2 virus is 5 min but the response is very small and raises concern for its claim. Why not provide a time range for the assay interrogation?
4. Fig 4. It was not clear if the heat-treated saliva samples received additional processing before application onto the sensor platform.
5. If the ultimate goal is to use saliva samples directly on the sensor, can the enzymes and other bioactive molecules present in saliva affect antibody functionality, hence the assay performance?
6. Authors should consider incorporating the following recent review article on coronavirus detection. “Demeke-Teklemariam et al. 2020. Biosensor and molecular-based methods for the detection of human coronaviruses: A review. Mol Cell Probes. 2020 Dec; 54: 101662”.