Impact and Occurrence of Herpesvirus and Aspergillosis Superinfection in Patients with Severe COVID-19 Pneumonia

Round 1

Reviewer 1 Report

The manuscript has a good structure, the introduction describes the background according to cited references.

Study design is well structured, results support the conclusion.

I find the manuscript suited for publication.

I do not have detailed comments.

Author Response

Dear Reviewer,

 

Thank you for your thoughtful review and for recognizing the structure and rigor of our manuscript. We are pleased to hear that the introduction effectively sets the stage with relevant background information, and that you found the study design to be well-structured with results that support our conclusions.

 

We appreciate your positive evaluation and endorsement of the manuscript for publication. Your feedback reinforces our confidence in the relevance and solidity of our research.

 

Thank you once again for your supportive and constructive comments! We look forward to the possibility of our study contributing to the field and being shared with the wider academic community.

 

Best regards,

Antoinette Reichert

Reviewer 2 Report

Reichert and colleagues submit a report regarding superinfections in patients with severe Covid-19 pneumonitis.

Comments:

-          It’s odd that Figure 1, the consort diagram, has no patient numbers in the clinical deterioration and BAL/testing boxes. That’s not really how consort diagrams work. You should change the name of the “clinical deterioration” box to “no clinical deterioration”, and list how many patients that applied to. Then, among the remaining patients with clinical deterioration, the next sequential box down would be “no bronchoscopy”, and list the number of patients that applied to. That should then bring you down to the 61 patients included.

-          Figure 1 would work out better as a combination figure with 2 panels. The consort diagram would be on the left panel and stops with 61 patients included, since inclusion and exclusion have been met by the time you reach 61 patients. Then there should be a pie chart for the right panel. The last 4 rows of the consort diagram would be more informative as a colored pie chart.

-          Since your combined CAPA rate is 44%, readers will want you to speculate on the use of anti-mold prophylaxis in the discussion (see figure in Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies, Open Forum Infect Dis. 2024 Feb 6;11(3):ofae082. doi: 10.1093/ofid/ofae082. eCollection 2024 Mar. PMID: 38481428).   

-          In Figure 1, I would round all your percentage numbers to whole integers.

-          In Figure 1, you have plenty of horizontal room with this figure, so each box could be made wider so that there are only 2 rows of text in each box.  

-          “Aciclovir” is spelled “acyclovir”.

 

-          The sentence spanning lines 140-143 is missing a close parenthesis.

-          On line 147, “a active” should be “an active”.

-          On line 172, “Aspergillus” should be in italics.

-          Rewrite the sentence spanning lines 172-174:  “The hospital infection prevention team investigation into the cluster of Aspergillus spp. infections concluded that the possible rise of infections was unable to be traced back to either equipment hygiene or air and ventilation quality.”

 

 

 

Author Response

Dear Reviewer,

 

Thank you for your thorough review and constructive comments, which have significantly contributed to enhancing the clarity and depth of our manuscript. Below, I address each of your points:

1. Figure 1 and Consort Diagram: We appreciate your detailed feedback regarding the structure of Figure 1. Upon review, we realized that our original consort diagram did not effectively convey the progression of patient selection and categorization as intended. However, due to the lack of precise numbers for subgroups within the patients who did not undergo bronchoscopy, as you pointed out, we have decided to remove the consort diagram. In its place, we have included a pie chart, as suggested, to visually represent the distribution of the patient subgroups who underwent bronchoscopy, experienced clinical deterioration, or were excluded for specific reasons. This change will provide a clearer, more informative visualization of the patient selection process.
2. Anti-mold Prophylaxis Discussion: We have incorporated a discussion on the potential use of anti-mold prophylaxis, given the 44% combined CAPA rate observed. Your reference to the recent study in the Open Forum Infectious Diseases was invaluable. We have speculated on the implications of our findings in the context of this study, discussing how anti-mold prophylaxis might benefit similar patient populations in ICU settings.
3. Minor Adjustments to Figure 1: We have rounded off all percentage numbers to whole integers in the new pie chart to enhance readability. Additionally, the design of the figure has been adjusted to ensure that all text is clear and fits comfortably within the visual presentation.
4. Text Corrections: We have corrected the spelling of "aciclovir" to "acyclovir" as per American English conventions, added the missing close parenthesis, and corrected grammatical errors as pointed out in your review. "Aspergillus" has been italicized throughout the document to maintain consistency and adhere to scientific naming conventions.
5. Sentence Rewriting: The sentence describing the conclusions of the hospital infection prevention team has been rewritten for clarity and conciseness: " The inquiry conducted by the hospital's infection prevention team regarding the cluster of Aspergillus spp. infections elucidated that the observed escalation in infections could not be attributed to either equipment sanitation practices or the quality of air and ventilation systems."

We believe these revisions have strengthened the manuscript and have addressed the concerns you raised. Thank you once again for your insightful feedback and guidance!

 

Best regards,

Antoinette Reichert

Reviewer 3 Report

The manuscript describes a retrospective observational investigation of 61 mechanically ventilated patients with COVID-19 who underwent bronchoalveolar lavage due to clinical worsening. The authors analysed blood and respiratory samples, treatment and clinical outcomes. Among all studied patients, 34 had superinfections, with 18 having pulmonary aspergillosis, seven having herpes simplex virus infection, and nine having both infections.

I have one major comment:

Table 1 lists various patient parameters, however, the Reviewer does not see references to some of them in the Discussion section. E.g., did the BMI value affect the patient's condition, gender or age? In the Abstract there is only the laconic sentence “Baseline parameters did not predict superinfections.” The reviewer sees no evidence to support this conclusion.

I have a few minor comments:

1.      Please provide the full names of COVID-19 and SARS-CoV-2 in the Introduction section, and abbreviations in parentheses when they are first used.

2.      Please add a paragraph on Statistical Analysis in the Materials and Methods section.

3.      The reference notation (numbers) should be in square brackets. Please correct this throughout the text.

4.      If an abbreviation has already been introduced, it should be used in further parts of the text. Please rewrite the entire manuscript under this account (e.g., the abbreviation CAPA was introduced in line 47, so remove the full names from lines 129 and 190; review the manuscript for other abbreviations as well).

Author Response

Dear Reviewer,

 

Thank you very much for your comprehensive review and insightful comments on our manuscript. Your detailed feedback has been instrumental in enhancing both the clarity and depth of our study.

 

In response to your key observation regarding the insufficient discussion on certain baseline parameters and their influence on the outcomes of herpes reactivation and CAPA, I have incorporated a table of multiple regression analysis. This addition is intended to explicitly demonstrate these relationships, ensuring a clearer understanding of their impacts.

 

Regarding your specific comments:

 

I have included the full names of COVID-19 and SARS-CoV-2 in the Introduction, with abbreviations provided in parentheses upon their first appearance.

A detailed paragraph on Statistical Analysis has been added to the Materials and Methods section, aiming to improve the transparency and reproducibility of our analytical approach.

I have updated the reference notation across the manuscript to ensure that all references are consistently presented in square brackets.

The use of abbreviations has been standardized throughout the manuscript. For example, the abbreviation 'CAPA' is now uniformly used following its introduction.

We have thoroughly reviewed and implemented all other suggestions as appropriate.

 

Thank you again for your invaluable feedback, which has significantly contributed to the refinement of our manuscript!

 

Best regards,

 

Antoinette Reichert

Reviewer 4 Report

Dear Authors

 

thank you very much for this study.

Minor suggestions are in the pdf file.

kind regards

Minor suggestions are in the pdf file.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

 

Thank you for your constructive feedback and for your appreciation of our study.

 

In response to your comments, I have revised the manuscript to address the points you raised. Specifically, I have italicized all references to Aspergillus throughout the text to ensure proper scientific notation. Additionally, I appreciate your observation regarding the specificity of the galactomannan test for detecting Aspergillus rather than a broader range of fungi. I have amended the relevant sentence to clarify that this test is used specifically for Aspergillus detection, enhancing the accuracy and scope of the information presented.

 

Thank you once again for your insightful suggestions and kind words regarding our work!

 

Best regards,

Antoinette Reichert

Round 2

Reviewer 2 Report

None.

Line 161: Aspergillus is in italics but without a capital letter. Please address in correction of proofs.

Reviewer 3 Report

No comments.

No comments.