The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection
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Analysis of incident, longitudinal RNA viral loads in saliva and nasal swabs and culturable viral titers in nasal swabs collected twice-daily by a tricenarian male infected with SARS-CoV-2 revealed the ratio between viral load and viral titer can be five orders of magnitude higher during early infection than late infection.
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The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
Porter and colleagues present a paper that investigates the ratio between SARS-CoV-2 viral load and culturable viral titre in a single patient case study. They highlight well that the relationship between RNA viral load and infectious virus titre is not fully established and that it may differ dependent on stage of infection. This work is naturally of importance as it can dictate infection control strategies for epi- and/or pandemics by informing government policy. Overall, it has value to the community, but it does have severe limitations as laid out in the discussion. Below is a breakdown of my summary regarding different aspects when considering this paper for acceptance. Methodological rigour: This sort of study is hard to carry out given the involvement of patients and movement of infectious …
Comments to Author
Porter and colleagues present a paper that investigates the ratio between SARS-CoV-2 viral load and culturable viral titre in a single patient case study. They highlight well that the relationship between RNA viral load and infectious virus titre is not fully established and that it may differ dependent on stage of infection. This work is naturally of importance as it can dictate infection control strategies for epi- and/or pandemics by informing government policy. Overall, it has value to the community, but it does have severe limitations as laid out in the discussion. Below is a breakdown of my summary regarding different aspects when considering this paper for acceptance. Methodological rigour: This sort of study is hard to carry out given the involvement of patients and movement of infectious samples as well as the high containment required to culture and probe virus titres. It makes it very difficult to reproduce and the authors have noted this. Given that these data only derive from one patient, whilst comprehensive, it does not provide enough data for statistical analysis and to really test the hypothesis around viral load Vs viral titre. Presentation of results: The results are condensed into 1x figure panel. The main figure (1A) is very busy and is hard to follow given the colours used are very similar in nature. Equally, there is some data in the supplementary figures that could be moved to the main body of the article to give it more substance. Style/organisation of the paper: no overall comments, it is acceptable. Discussion: The authors have rightly included several limitations of the study, which is appreciated. However, I feel given the lack of power in the study, no real conclusions can be ultimately drawn from the work as 1x patient does not equate to population level values. Below I have listed things that need to be addressed by the authors: Major Comments: 1 - The abstract is of very poor quality and needs to be re-written following standard abstract guidance. 2 - Suggest authors re-think main figure 1A as it is difficult to decipher given the similar colours used. Suggest that they split the nasal and saliva samples up to make the figure less busy. Minor Comments: 1 - Line 68. Authors have analysed data from one patient but mention 2x were eligible. Please clarify.
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Please ONLY put comments for the Author(s) in Manuscript number: ACMI-D-23-00188 Title: The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection Access Microbiology Reproducibility of the findings should be documented. Were the findings dependent on the viral strain? 6/24
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript …
Comments to Author
Please ONLY put comments for the Author(s) in Manuscript number: ACMI-D-23-00188 Title: The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection Access Microbiology Reproducibility of the findings should be documented. Were the findings dependent on the viral strain? 6/24
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
This paper is a single patient case study. It show for this patient and the specific methods used that the ratio of the viable count of viruses varies with Covid load by up to 5 orders of magnitude during the course of an infection. The take-home message is clear, namely that knowledge of the viral load as measured by molecular techniques cannot be used as a reliable measure of the risk of viral transmission. The Discussion section lists four conclusions from the study, albeit with a subsequent list of caveats. For example, the authors recognise that many factors might have contributed to the results obtained, not least possible in unreliable ways that some samples were taken, stored and transferred. However, three human genes were used as baselines to support the viral data. The results from …
Comments to Author
This paper is a single patient case study. It show for this patient and the specific methods used that the ratio of the viable count of viruses varies with Covid load by up to 5 orders of magnitude during the course of an infection. The take-home message is clear, namely that knowledge of the viral load as measured by molecular techniques cannot be used as a reliable measure of the risk of viral transmission. The Discussion section lists four conclusions from the study, albeit with a subsequent list of caveats. For example, the authors recognise that many factors might have contributed to the results obtained, not least possible in unreliable ways that some samples were taken, stored and transferred. However, three human genes were used as baselines to support the viral data. The results from these controls were consistent from sample to sample. Furthermore, data from a previous study by another group (reference 25) fully support the conclusions in this manuscript and are presented in the supplementary information. The current manuscript represents an extension of information to that already presented by the authors in reference 30. This raises the critical question why this small extension based upon what might ultimately prove to be anecdotal data merits publication. For this reviewer the answer to this question is that data on the progression of viral load and viability for individual patients from an early stage of infection is extremely difficult to obtain. Normally this would be possible only after the infection is well established and the viral load is already extremely high. The Discussion makes the obvious weaknesses of the study transparent and the overall conclusion is significant. Subject to a few minor modifications listed below, the case study is suitable for acceptance by the journal Access Microbiology. Throughout the manuscript. Are "data" singular or plural? Surely the latter, so plural verbs are required. Line 68. Should the word "both" be deleted as only one patient was involved in this study? If not, please rephrase. Lines 126 to 128. I found this sentence confusing. Please rephrase. ONLY put comments for the Author(s) in here
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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