Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period

Round 1

Reviewer 1 Report

The article entitled Clinical determinants of the duration of SARS-CoV-2 viral 2

shedding in COVID-19 patients: a single-center observational study is a retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was per- 18 formed from June to December 2021. In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. This article is well design, with good presented and analyzed results. Hence, there is some suggestions for improving:

1.     In Section Introduction, please update the latest information from 2023. 

2.     Figure 1 has some limited technical errors, please correct. Also resolution of picture must be increased.

3.     In Section Methods please be precise how many hospitals were included. 

4.     How you can explain that about 25% percent of participants were elderly above 60 years old? Optional to exclude these patients wince they could provide different results from younger patients. Lines 103-118.

5.     It is necessary to divide patients according to the age groups and to analyze all results according to that (clinical symptoms, disease severity, comorbidities, treatment etc)

6.     The main limitation is small number of patients even that was pandemic. 

7.     Please add results about the outcome (survived, fatal, prolonged hospitalization etc)

 

Comments for author File: Comments.pdf

Author Response

1. In Section Introduction, please update the latest information from 2023. 

Response: We have updated the COVID-19 latest information globally and the Indonesia situation in lines 44-47.

2. Figure 1 has some limited technical errors, please correct. Also resolution of  picture must be increased.

Response: We have corrected figure 1 in the revised manuscript

3. In Section Methods please be precise how many hospitals were included. 

Response: This study was conducted in a single center/one hospital, as shown in line 74

4. How you can explain that about 25% percent of participants were elderly above 60 years old? Optional to exclude these patients since they could provide different results from younger patients. Lines 103-118.

Response: This phenomenon might be related to the disease severity pattern in this study, which was dominated by mild illness (43.83%). The elderly tend to have a severe or critical disease that needs ICU treatment and is not included in this study. The option to exclude the elderly from this study is not possible because we want to analyze the impact of age on the viral shedding duration. 

5. It is necessary to divide patients according to the age groups and to analyze all results according to that (clinical symptoms, disease severity, comorbidities, treatment etc)

Response: we divided the patients according to the duration of viral shedding as we aim to ascertain the influence of several parameters on the duration of SARS-CoV-2 shedding. We do not intend to study the impact of age on COVID-19 symptoms, severity, comorbidities, or treatment specifically.

6. The main limitation is small number of patients even that was pandemic. 

Response: We have added the small sample size as our study limitation in line 318

7. Please add results about the outcome (survived, fatal, prolonged hospitalization, etc)

Response: We have added the outcome such as the number of cured patients and death, length of stay, and the mean duration of viral shedding in table 1, and described in lines 138-142.

Reviewer 2 Report

·         Generally, the writing and arguments in the paper are technically valid and the text is easy to read. This work constitutes a good contribution to the field.

·         The title is relevant and informative.

·         The abstract matches the whole text. It indicates the main topics and results.

·         The research question is for me clearly outlined.

·         The introduction is concise and the references are up to date.

·         The author has described the aim of the study at the end of the introduction.

·         The design and statistical analysis described in the methods section are in accordance with the objective of the study.

·         The intended sample size of this study is clear. I appreciate its mention in the limitation section;

·         The results and mainly Table 2 are not well described,

·         To assure transparency, the authors reported the limitations of the study.

·         The Conclusion section is good but very short: Go returned over the primary records you covered in subheadings and reiterate them. Summarize the essential information mentioning the main results so the readers recognize what to take away from your study.

·         Some statements need references mentions, for example:

o   Lines 144-145: “The clinical symptoms observed are similar to those reported by Qi et al., including cough, fever, and shortness of breath.” Please specify the reference. The reference 20?

 

o   Lines 156 and 157: “Another study reported a median viral shedding of 20 days with the deaths of approximately 54 people”. Which one? Please specify.

Author Response

Dear reviewer,

Thank you for your suggestion on our manuscript. The following below are several points for revision according to your suggestions:

1.   The results and mainly Table 2 are not well described
   • Response: We have updated the result in more detailed in lines 145-169
2. The Conclusion section is good but very short: Go returned over the primary records you covered in subheadings and reiterate them. Summarize the essential information mentioning the main results so the readers recognize what to take away from your study.
   • Response: We have improved the conclusion section in lines  320-327

3.  Lines 144-145: “The clinical symptoms observed are similar to those reported by Qi et al., including cough, fever, and shortness of breath.” Please specify the reference. The reference 20?

   • Response: thank you for your correction. There was a mistake in the reference citation. We updated the citation as shown in lines 191-194.
4.  Lines 156 and 157: “Another study reported a median viral shedding of 20 days with the deaths of approximately 54 people”. Which one? Please specify.
   • Response: thank you for your correction. We have revised the sentence as shown in lines 203-208.

Reviewer 3 Report

1. What is the justification for using 13 days as criteria for categorization?

2. Authors categorized the disease severity into mild, moderate, and severe. In the multivariate analysis, it would be good to show moderate and severe groups separately, compared to the mild group (OR 1).

3. In the multivariate analysis, data for gender is not presented in Table 3.

4. Some cells have been left empty under Stepwise analysis. Is there any specific reason for it?

Author Response

Dear Reviewer,

Thank you for reviewing our manuscript. The following below are points for manuscript revision according to your suggestions:

1. What is the justification for using 13 days as criteria for categorization?

Response: the categorization for bivariate analysis was according to the mean duration of SARS-CoV-2 RNA shedding, which was 13 days. We have written this issue in the method section, lines 112-113.

2. Authors categorized the disease severity into mild, moderate, and severe. In the multivariate analysis, it would be good to show moderate and severe groups separately, compared to the mild group (OR 1). 

Response: Thank you for your suggestion. The disease severity was analyzed as one variable in the bivariate analysis, with p 0.012, so in the multivariate analysis, it continued to be processed as a single variable, with p=0.001, OR 3.05. After the stepwise analysis, the result was still significant, with p=0.007, and aOR=2.94.

3. In the multivariate analysis, data for gender is not presented in Table 3.

Response: Table 3 presented the variables to be included in the multivariate analysis. The variables included were chosen from the bivariate analysis that was significant (p<0.25), which were disease severity, dyspnea, bilateral pulmonary infiltrates on chest x-ray, hypertension, diabetes, and treatments including oxygen supplementation, antibiotic, oral antiviral, and corticosteroid. We have written this issue in the method section lines 115-118.

4. Some cells have been left empty under Stepwise analysis. Is there any specific reason for it?

Response: stepwise analysis in the multivariate analysis only processed the variables that were statistically significant (p<0.05). The variables that have p>0.05 were not continued for further analysis. We described this analysis in the result section lines 176-180.