Respiratory Viruses Coinfections During the COVID-19 Pandemic in Southern Brazil

Round 1

Reviewer 1 Report

• Suggestions to Author/s

1. Dear Dr. Henrique Borges da Silva Grisad, as a selected reviewer, I made the prompt check of your excellent article: “Respiratory Viruses Co-infections during the COVID-19 Pandemic in Southern Brazil” and found it: (x) Excellent, accept the submission (5)
2. During the prompt check, some minor mistakes were identified and corrected in red. Please accept the corrections so that you can highlight the red text in black.
3. In the Reference list, in some of the articles, the doi was missing. So, they were found by the reviewer with the help of Google. They are highlighted with red colour.
4. The PDF article was not converted into a doc. This was done by the reviewer, who, with the help of Convertio software, converted the PDF to DOC, enabling the corrections.
5. In general, it can be said that this is an important scientific article that, when it is published it will make a strong impact in the scientific literature of this field, together with the high number of citations.

Article Title: Respiratory Viruses Co-infections during the COVID-19 Pandemic in Southern

                          Brazil.

Reviewer’s Name: Dr. Bratko Filipič

v                  Recommendation to Editor (Please mark “x” for appropriate option)
(x) Excellent, accept the submission (5) ( ) Good, accept the submission with minor revisions required (4) ( ) Acceptable, revisions required (3) ( ) Resubmit for review, major revisions required (2) ( ) Decline the submission (1)
v                  Evaluation  (Please evaluate the manuscript by grade 1-5)
5=Excellent    4=Good    3=Average    2=Below Average    1=Poor
Items	Grade
Contribution to existing knowledge	5
Organization and readability	5
Soundness of methodology	4
Evidence supports conclusion	5
Adequacy of literature review	3
Important findings: 1. Dr. Henrique Borges da Silva Grisad with the help of his coworkers has prepared an important research article: “Respiratory Viruses Co-infections during the COVID-19 Pandemic in Southern Brazil.” 2. Even after the official WHO declaration putting an end to the public health emergency of international concern related to COVID-19, scientific data still needs to be explored in search of answers that can elucidate the variations in the clinical presentation   among patients and in the epidemiological aspects of SARS-CoV-2. One of these explorations involves the importance of co-infection with other respiratory pathogens. 3. Faced with the possibility of other respiratory pathogens co-infecting patients and modifying their clinical response to SARS-CoV-2, some researchers have explored this line of investigation. 4. Thus, the present study employed RT-qPCR to assess the presence of  Human Adenovirus (HAdV), Influenza A (Flu A), Influenza B (Flu B), Human Metapneumovirus (HMPV), Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV), and  Para influenza Virus (PIV). 5. A total of 187 (men and women) nasopharyngeal samples from adult patients exhibiting respiratory symptoms were collected between February 2021 and November 2022 at the University Hospital Polydoro Ernani de São Thiago in Florianópolis, SC in Brazil.   6. Of the 187 samples from adult patients (men and women) with non-serious respiratory symptoms, one test was positive for HAdV, one for Flu A, one for HMPV, four for RSV, 35 for HRV, and five for PIV. Thus, the authors’ data corroborates Kim and collaborators who, in 2020, had already demonstrated higher report rates of HRV and RSV infections in patients with respiratory symptoms but undetected for SARS-CoV-2. 7. Severe Acute Respiratory Syndrome (SARS) is a more aggressive infection that can lead to hospitalizations and death. In this study, the largest number of infections reported, except for SARS-CoV-2, was by HRV. This discrepancy in the data can be explained in part by authors’ sampling, which did not cover severe cases, but only classic flu symptoms, a profile different from that monitored by public agencies. Interestingly, although the authors’ results demonstrate only one sample co-infected with SARS-CoV-2 and Flu A, epidemiological data from DIVE reported 72 deaths in the state of Santa Catarina due to SARS  caused by Flu A. Thus, they hypothesize that this difference is due to the population group of the study, which were symptomatic adults without enough clinical severity to justify hospitalization due to classic signs of SARS. 8. Between February 2021 and November 2022, patients were tested for Flu B, HMPV, RSV, HRV, and PIV at the University Hospital Polydoro Ernani de São Thiago of the Federal University of Santa Catarina, located in Florianópolis, Santa Catarina in Brazil. During this period, HRV, PIV, RSV, and MPV were detected in patients who were not infected with SARS-CoV-2, in addition to detecting HAdV, Flu A, and HRV co-infecting patients detected for SARS-CoV-2. 9. All these data in conclusion demonstrate the importance of monitoring infectious pathogens that affect the respiratory system, in addition to SARS-CoV-2, aiming to identify the population's epidemiological pattern to improve prevention and make therapeutic approaches as individualized as possible.
v                 Weaknesses 1. In the Reference list, in some of the articles, the doi was missing. So, they were found by the reviewer with the help of Google. They are highlighted with the red color. 2. The PDF article was not converted into doc. This was done by the reviewer, who with the help of Convertio software converted PDF to doc, so enabling the corrections.

Comments for author File: Comments.pdf

Author Response

Thank you for your suggestions. We greatly appreciate your review and your kindness in including the missing DOI numbers.

Author Response File: Author Response.pdf

Reviewer 2 Report

This study roughly listed the proportion of adult patients with respiratory symptoms who were positive and negative for SARS-CoV-2 respiratory virus, as well as the proportion and difference of co-infection with other respiratory pathogens (except for human rhinovirus, which is a common virus, all other viruses are completely different between the two groups). The significance of the study lies in that co-infection can change the prognosis of patients and increase the need for mechanical ventilation during treatment. The shortcomings and aspects that need to be improved in the study: it did not specify the gender and age differences, did not indicate the number of samples per month, and did not point out the number of double or more infections (it would be better to present it in a table form). It did not reasonably explain the reason for the significant difference in the co-infection rate of SARS-CoV-2 respiratory virus and influenza A in the same state during the same period. It did not explain in detail why the types of viruses co-infected in SARS-CoV-2 respiratory virus infected and non-infected patients were completely different except for human rhinovirus (which also had a significant difference in infection rate).

This study roughly listed the proportion of adult patients with respiratory symptoms who were positive and negative for SARS-CoV-2 respiratory virus, as well as the proportion and difference of co-infection with other respiratory pathogens (except for human rhinovirus, which is a common virus, all other viruses are completely different between the two groups). The significance of the study lies in that co-infection can change the prognosis of patients and increase the need for mechanical ventilation during treatment. The shortcomings and aspects that need to be improved in the study: it did not specify the gender and age differences, did not indicate the number of samples per month, and did not point out the number of double or more infections (it would be better to present it in a table form). It did not reasonably explain the reason for the significant difference in the co-infection rate of SARS-CoV-2 respiratory virus and influenza A in the same state during the same period. It did not explain in detail why the types of viruses co-infected in SARS-CoV-2 respiratory virus infected and non-infected patients were completely different except for human rhinovirus (which also had a significant difference in infection rate).

Author Response

Comment 1: “…it did not specify the gender and age differences, did not indicate the number of samples per month, and did not point out the number of double or more infections (it would be better to present it in a table form).”

 

Response: Thank you for your comment. The patient's age and gender can be found in Table S1, as well as the sample's date of collection and full results, including double or multiple infections.

 

Comment 2: “It did not reasonably explain the reason for the significant difference in the co-infection rate of SARS-CoV-2 respiratory virus and influenza A in the same state during the same period.”

 

Response: We appreciate your insight. Yes, it was seen that Influenza A Virus was only detected in SARS-CoV-2 positive patients; however, this is an exploratory study, aiming to demonstrate the co-infections present in this period, as compared to other authors' findings. But surely, further research would be of great value to understand this relationship between the viruses.

 

Comment 3: “It did not explain in detail why the types of viruses co-infected in SARS-CoV-2 respiratory virus-infected and non-infected patients were completely different, except for human rhinovirus (which also had a significant difference in infection rate).”

 

Response: Thank you for your suggestion. Agreed, but as above-mentioned, this study has an exploratory nature, thus not venturing further into the explanation of the events found during this research. Yet still, it would be of huge benefit to understand the dynamics leading to these different co-infections happening in SARS-CoV-2-positive and SARS-CoV-2-negative patients.

Author Response File: Author Response.pdf

Reviewer 3 Report

Make corrections in the attached file

Please add some references

Comments for author File: Comments.pdf

Author Response

Thank you for your suggestions. We greatly appreciate your review.

Author Response File: Author Response.pdf