Rapid Serological Test for COVID-19, One-Step-COVID-2019: Accuracy and Implications for Pandemic Control

Round 1

Reviewer 1 Report

In the manuscript by Menezes-Junior et al, the authors studied the accuracy of rapid Covid-19 test kit with ELISA. The rapid Covid-19 kit is One-Step-COVID-2019, based on serological test for IgM-IgG antibodies.  The authors conducted a population-based serological survey with 593 qualified adult samples in 2020. An in-house ELISA for IgG against the spike protein was used as reference standard. The authors found significant differences between the test results by McNemar’s test. The One-Step-COVID-19 test showed low sensitivity (27-31%) but high specificity (90-97%) with poor agreement (kappa~0.3) while the ELISA showed an infection prevalence of ~11%.  The authors concluded that the One-Step-COVID-2019 rapid test demonstrated inadequate performance and unsuitable for effective serological surveillance.

General speaking, the writing is clear and the data are presented to support the arguments. The design is easy to follow. The authors also discussed if IgM ELISA test performed as the rapid test based on IgG and IgM and the authors only used IgG ELISA in the current studies.

I don’t have concerns for this manuscript, it is ready for publication consideration.

I don’t have concerns for this manuscript, it is ready for publication consideration.

Author Response

Dear Reviewer,

We sincerely appreciate your careful reading and the time you dedicated to reviewing our manuscript . We are grateful for your positive comments on the clarity of our writing, the presentation of our data, and the design of our study.

Your comments encourage our continued commitment to high-quality research and the improvement of diagnostic tools for pandemic control.

We are available for any further observations or suggestions that may arise. Thank you once again for your attentive review and valuable feedback.

Sincerely,

Reviewer 2 Report

The authors explored the effectiveness of a new serological test for detecting COVID-19, highlighting its importance in combating the pandemic. The study found a higher seroprevalence of SARS-CoV-2 among less educated individuals and those not working from home. Additionally, a higher seroprevalence was observed exclusively among women using the ELISA test. However, the authors indicated that the One-Step-COVID-2019 rapid test was not suitable for effective serological surveillance due to its low sensitivity and reliability.

Here are some questions and suggestions:

 

1) The authors should give more detailed information of One-Step-COVID-2019-Test to explain  its low sensitivity and reliability, compared with the well established serological methods.

2) Line 182-184, the authors declared that One-Step-COVID-2019-Test can be utilized in conjunction with other data, such as disease symptoms, to enhance the probability of an accurate diagnosis. However, However, the symptoms of COVID-19 are very diverse and lack specificity; on the other hand, many individuals may have already recovered during serological surveys. Therefore, I believe this issue needs to be re-discussed by the authors.

3) The authors need to provide more background on the application of this method. Since it is not suitable for serological surveillance, the significance of this article requires further discussion.

Author Response

Dear Reviewer,

We would like to express our sincere thanks for the valuable considerations and suggestions you have provided. Your feedback has been instrumental in considerably improving the quality of our work and has ensured a more thorough and rigorous review of the manuscript.

In response to your comments, we have made the requested changes and included a point-by-point response letter, in which we justify and explain the changes made. The main changes include:

1. Expanded Methodology: We have added detailed information on both the One-Step-COVID-2019 Test and the reference ELISA, including their principles, result interpretation, and quality control mechanisms.

2. Clarified Test Limitations: We revised the text to emphasize that while the One-Step-COVID-2019 Test shows marginally better accuracy in symptomatic individuals, its overall performance remains inadequate. We stress the importance of combining rapid tests with more specific diagnostic methods like PCR for accurate COVID-19 diagnosis and surveillance.

3. Historical Context: We included additional context about the One-Step-COVID-2019 Test's role as one of the first rapid tests approved in Brazil for early COVID-19 serological assessment. We discussed its historical significance and limitations in terms of sensitivity and accuracy.

Thank you again for your insightful comments, which were crucial in enhancing the quality of our work.

Best regards,

Author Response File: Author Response.pdf

Reviewer 3 Report

I appreciate the author's idea of looking for rapid, effective tests to combat COVID-19 pandemic, it's an interesting subject. As a comment, I think the author should have also compared with RT-PCR for a better evaluation of his technique, if not he should justify why RT-PCR was not done? 

1- In the abstract section, it might be better to add a background section in which the objective can be announced.

2- Materials and Methods : What about Ethics statement?

3 - Results : Table 1 quoted as a reference does not cover all results, it would be better to quote it higher up first, e.g. insert it in line 134 : the overall results for all individuals were presented in the table 1 as follows ...

Author Response

Dear Reviewer,

Thank you for your valuable feedback and insightful comments. We greatly appreciate your time and effort in reviewing our manuscript.

In response to your suggestions, we have made several key revisions to enhance the clarity and quality of our work. A point-by-point response document is attached to the system. 

These revisions aim to provide a clearer and more comprehensive understanding of our study. We hope these changes meet your expectations and improve the overall quality of the manuscript.

Thank you once again for your constructive feedback.

Best regards,

Author Response File: Author Response.pdf

Reviewer 4 Report

In this manuscript entitled ‘Rapid serological test for covid-19, One-Step-COVID-2019: ac-2 curacy and implications for pandemic control’, authors reached a very plausible conclusion by evaluating the accuracy of a rapid serological test method with SARS-CoV-2 spike protein-based ELISA as the reference. Although the workload is respectively considerable, the novelty and significance of this manuscript are limited. In addition, the conclusion is not well-supported by the evidence and thus, this manuscript does not meet the criteria for the COVID.

 1. It might have been interesting during the very early stage of COVID-19, when very limited knowledge on the COVID-19 test was available. However, given the widespread vaccination and accumulated knowledge on COVID-19, serological test are now of little to no relevance to pandemic control. 

2. It is quite unusual to use ELISA as the gold standard, since the accuracy of ELISA, especially in-house ELISA versions, has not been consistently high and stable enough in previous studies. As a result, the findings in this paper, based on an unrealizable control, are not trustworthy.

3. The samples used in this study are not reasonable. Previous studies have well characterized the SARS-CoV-2-specific antibody profiles in both naturally infected patients and vaccine recipients. Authors should not use sera with unclear background. Instead, they should use sera collected before COVID-19 pandemic as negative ones and use sera collected from patients recovered from COVID-19 as positive ones.

4.   Most characteristics except for symptoms of covid-19 listed in Table 2 have nothing to do with the main points of the text. 

 

1. The algorithm and equations used to calculate sensitivity, specificity, PPV, NPV, AUC, kappa should be given in the method part

2.  One-step-Covid-19 is not properly shown in figure 1. Authors should also explain the meaning of ‘Celer Wondfo’ in figure 1.

 

Author Response

Dear Reviewer,

Thank you for your valuable feedback and insightful comments. We greatly appreciate your time and effort in reviewing our manuscript.

In response to your suggestions, we have made several key revisions to enhance the clarity and quality of our work. A point-by-point response document is attached to the system. 

These revisions aim to provide a clearer and more comprehensive understanding of our study. We hope these changes meet your expectations and improve the overall quality of the manuscript.

Thank you once again for your constructive feedback.

Best regards,

Author Response File: Author Response.pdf