Post Publication Independent Review of

"Viral dynamics in mild and severe cases of COVID-19"

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Post Publication Independent Review of "Viral dynamics in mild and severe cases of COVID-19"

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Post Publication Independent Review of

"Viral dynamics in mild and severe cases of COVID-19"

Yang Liu, Li-Meng Yan, Lagen Wan, Tian-Xin Xiang, Aiping Le, Jia-Ming Liu et al.

Published: March 19, 2020 DOI:

Review Comments:

1. Title inappropriate. Mild & Severe has been classified by the Authors later in the Manuscript. No Universal Standard has been cited. Consequently, authors need not have included the keywords mild and severe in the title, for the reason that these are the first few research articles that are appearing on COVID-19. Authors cannot enforce Mild and Severe conditions so early. Else, they should have indicated subjective conditions in the title instead of generic objectivity.

2. Authors declare COVID-19 as a new pandemic disease in the first line of the manuscript. Citation required. Else, they could have substantiated in the manuscript that it is a pandemic. Heightening human anxiety in the first line of a research manuscript may amount to author bias.

3. In the second sentence of the manuscript, authors are disclosing the information that they had previously published on SARS-CoV-2. Was there any urgent necessity for the authors to declare to the scientific community that they have previously published on SARS-CoV-2 and they are now publishing on COVID-19. Do the authors intend to indicate that they are an authority on the area and related areas and consequently all that they publish needs to accepted as it is? When any simple search on or Google Scholar or any other internet search engine can throw light on the previous research exploits of the authors, why is there a necessity for the authors to indicate that they have published on SARS-CoV-2, right in the second sentence of this manuscript. Again, this might amount to author bias.

4. This manuscript has been declared as published on March 19, 2020. In third sentence of this manuscript, authors are citing Reference 3 with DOI:10.1056/NEJMoa2002032. Cited article is Clinical Characteristics of Coronavirus Disease 2019 in China

List of authors. Wei-jie Guan, Ph.D., Zheng-yi Ni, M.D., Yu Hu, M.D., Wen-hua Liang, Ph.D., Chun-quan Ou, Ph.D., Jian-xing He, M.D., Lei Liu, M.D., Hong Shan, M.D., Chun-liang Lei, M.D., David S.C. Hui, M.D., Bin Du, M.D., Lan-juan Li, M.D., et al., for the China Medical Treatment Expert Group for Covid-19*

Extract from cited article:

medical records and compiled data

as reported to the National Health Commission between December 11, 2019, and January 29, 2020; the data cutoff for the study was January 31, 2020

4a. Did the National Health Commission certify that the data reported is error-free? Is National Health Commission Certification attached to cited manuscript DOI:10.1056/NEJMoa2002032 ?

4b. Attention is drawn to

(i) Jan 31, 2020:

Total Cases: 11,791.

Daily New Cases: 2,099.

Active Cases: 11,289.

Total Deaths: 259

Daily New Deaths: 46

Newly Infected vs. Newly Recovered: 2,099 vs 72

Outcome of Cases (Recovery or Death): Recovery rate vs death rate: Not Available

(ii) Peak Rates:

Total Cases: 81, 218 as on 25.03.2020

Daily New Cases: 14,108 as on 12.02.2020

Active Cases: 58,016 as on 17.02.2020

Total Deaths: Gradient of curve indicates gradual slope upto Feb 16, further becoming more gradual until Feb 22, and growing still more gradual post Feb 23.

Daily New Deaths: Peaks observed at Feb 12, Feb 14, Feb 15, Feb 18, Feb 23. Graph is not steady. Waxing and Waning nonsystematic.

Newly Infected vs. Newly Recovered: New Cases Peak at Feb 12. New Recoveries Peak at Feb 27. Also noted that Lowest Recovery does not coincide with New Cases Peak and Lowest New Cases does not coincide with Peak New Recoveries. Nonsystematic behaviour observed.

(iii) Total Cases as on 25.03.2020: 81,218

4c. DOI: 10.1056/NEJMoa2002032

Quote "As of February 25, 2020, a total of 81,109 laboratory-confirmed cases had been documented globally.5,6,9-11" End of Quote

Quote "We obtained the medical records and compiled data for hospitalized patients and outpatients with laboratory-confirmed Covid-19, as reported to the National Health Commission between December 11, 2019, and January 29, 2020; the data cutoff for the study was January 31, 2020" End of Quote

Did the authors draft the article after Feb 25, 2020, coz there is no possibility that they can include a futuristic statistic as globally documented data. Consequently, this manuscript should have been drafted after Feb 25, 2020. If this manuscript has been drafted after Feb 25, 2020, why was the data cut off for the Study fixed as January 31, 2020?

Quote "Written informed consent was waived in light of the urgent need to collect data. " End of Quote.

Read together with, when written informed consent itself was given an allowance and bypassed, then except for the data of the last few hours, the rest of the data would have been available even upto Feb 25, 2020 (minus a few hours, perhaps upto Feb 24, 2020).

Attention is drawn to the phenomena observed under 4b (i-iii), it raises a question whether some very significant clinical information has been left out? If so, what would be the significance of the outcome of the results of such a manuscript which is suspected to have left behind very significant clinical information?

4d. Attention is drawn to Article Metrics

Social Media seems to have been enchanted by this article with questionable results

Twitter 24420

Facebook 32

Blog 35

Didnt anyone check whether this article can be relied upon? What would be the spread of information via so many twitter and facebook feeds and blogs?

On top of it, 67 citations for this research article? Didnt other researchers or authors start getting the same questions that crop up here? How could they blindly follow this research article?

5. Resuming again from Comment 3., article "Viral dynamics in mild and severe cases of COVID-19" also depends on the above article discussed in comment 4., and authors are banking heavily on the above article by citing it in the third sentence of their manuscript. When the merit of the cited article raises so many questions as in comment 4., how could the authors bank on the above article? When the merit of the base article becomes questionable, wont the merit of this article (that banks on the base article) also become questionable?

6. Quote "Findings from Feb, 2020, indicated that the clinical spectrum of this disease can be very heterogeneous." End of Quote. Article analysed in Comment 4 is indicated as reference for this statement. When the original article itself has restricted data upto Jan 31, 2020, how can this article indicate Findings from Feb, 2020, when this banks on the original article whose data is only upto Jan 31, 2020? Does this indicate carelessness by the authors? Further, another question arises, that when the foundation itself is shaky, how can another article ride piggy back on it, especially by citing it erroneously too? Suspected propagation of error and amplication of error from foundation article to this article?

7. Quote "Here, we report the viral RNA shedding patterns observed in patients with mild and severe COVID-19". This is the 4th sentence in the article. So far the authors have not defined or cited definition of mild and severe with reference to COVID-19. Should mild and severe be read as mild and severe for all conventional diseases or should mild and severe be read on a different scale with relevance to COVID-19? Authors are suggested to first introduce/explain various parameters that they would be using in the manuscript prior to using them? Else, the reader might get accustomed to the defines mild and severe and accept everything that follows without any scientific inquiry. Suspected Author bias.

8. Quote "76 patients admitted to the First Affiliated Hospital of Nanchang University (Nanchang, China) from Jan 21 to Feb 4, 2020, were included in the study" End of Quote

Quote "Coronavirus disease 2019 (COVID-19) is a new pandemic disease." End of Quote.

As per the Authors statement, the COVID-19 is a new pandemic disease. For investigating a pandemic disease (as per the authors statement), would a sample population of 76 be sufficient? Wouldnt the sample population be considered as insufficient to be considered as representative of the whole? In such a case, wouldnt the findings be trivial?

9. Quote "Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected.4" End of Quote. The authors are referring to cited as Reference no. 4 and stating that Parameters across mild and severe groups were the same, except that patients in the severe group were older than those in the mild group, which was as expected as per Reference no. 4, which is published online on Feb 24, 2020.

9a. Preliminary examination of indicated the following interesting extract

Quote "In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020" End Quote

The sample population itself was only 52 and they were adult and critically ill.

Further, Quote "The mean age of the 52 patients was 59·7" End Quote

So, if a sample population was 52 adult patients with a mean age of 59.7, enrolled for study when they were already critically ill, then, however experimented, the finding is going to be only about adult patients who are critically ill, and the finding cannot reflect any younger age group who were not critically ill, coz the choice was adult patients who were critically ill. Stated in simple terms, the spoon can serve only what is already there in the vessel.

9b. Reading Comment 9 & 9a together, what do the authors mean that they investigated and found that older patients were in the severe group as expected, based on results on another study which studied only older patients. Isnt this absurd/ridiculous? Do the authors expect that the reader will be so careless to accept whatever is written? Author bias suspected.

9c. On top of it, reading together Comment 4d, so many people seem to have become so engrossed by this article, flooding social media and causing such widespread dissemination of such questionable research reporting?

10. Quote "Overall, our data indicate that, similar to SARS in 2002–03,6 patients with severe COVID-19 tend to have a high viral load and a long virus-shedding period. " End of Quote. Authors seem to be banking their results on Reference No. 6

10a. Preliminary Examination of indicates that

Quote "It is difficult to compare case-fatality ratios between different cohorts and countries. Differences in distribution in terms of age, sex, disease activity (reflected by lactate dehydrogenase level) and proportion of cases confirmed by virologic tests have been cited as possible reasons for differences in case-fatality ratios.12 Our results suggest that such variation should be interpreted in light of host factors (age and comorbidity) and viral factors (viral load). In future studies, viral load should be monitored and analyzed, so that it can be considered in the interpretation of outcome data." End Quote.

10b. The article that the authors are banking on as indicated in Comment 10a does not directly emphasize on high viral load and long virus-shedding period but rather indicates that variations can be there due to differences between cohorts (societal/community populations), countries, age, sex, disease activity. Further it emphazises that viral load should be monitored and analyzed, so that it can be considered in the interpretation of outcome data.

10c. Reading together Comments 10, 10a and 10b, the authors are trying to bank significance on high viral load and long virus-shedding period on another article which states that there can be differences due to various factors and viral load needs to be monitored and analysed. In such a case, what is the point that the authors are trying to make by attempting to add significance to concerns which might manifest differently? So, does it mean that patients with severe COVID-19 can have variability due to viral load and virus-shedding period? If there is variability, then what is the significance of the findings of this paper?

11. Quote "This finding suggests that the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis." End Quote.

Reading together Comment 10, 10a-c, when the finding itself has lost its significance, how can the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis?

12. Apart from insight obtained via Comment 10a, there doesnt seem any significant research information in this article. Or have the authors failed to defend their point? However, Comment 10a stands out, and that seems to show a brighter side. Perhaps, the key to handling COVID-19 lies in Comment 10a. Exploitation of significance of Comment 10a might show a way for the world to win the battle against the COVID-19.

13. In the midst of such storms caused by COVID-19, have we accidentally identified "A faint beam of light at the end of the tunnel.... " !!!

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