Impact of SARS-CoV-2 Pandemic and Lockdown on the HRSV Circulation: Experience of Three Spoke Hospitals in Northern Italy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

General comments:

The paper entitled “Impact of SARS-CoV2 pandemic and lockdown on the RSV circulation: experience of three spoke hospitals in northern Italy” offers new insights into comprehending the changed epidemiology of RSV circulation during and after the SARS-CoV-2 pandemic due to the implementation of mitigation strategies.  The study involved three Spoke Pediatric Departments and included all infants under one year of age hospitalized for HRSV bronchiolitis in three different study periods. The main aim of the study was to analyze the temporal trend of HRSV, clinical, and epidemiological characteristics. It presents interesting findings about the severity of the infections, which is crucial in understanding HRSV bronchiolitis.

 Major points

Page 3 line 92: The authors divided the included patients into two groups: group A hospitalized before the SARS-CoV-2 Pandemic (from September 1, 2017 to March 31, 2018; from September 1, 2018 to March 31, 2019; from September 1, 2019 to March 31, 2020) and Group B hospitalized after the period of Pandemic (from September 1, 2021 to March 31, 2022; from September 1, 2022 to March 31, 2023). The authors need to change the division of the patients into different groups that will be unified throughout the whole article as well as in the results section (3.3. RSV prevalence). 

 

1.      A very big limitation is missing data. From the previous research from Slovenia which is a neighboring country, we can see a very high number of HRSV-positive cases from July to December 2021 (Virant MJ. 2023. Changes in HRSV Epidemiology but Not Circulating Variants in Hospitalized Children due to the Emergence of SARS-CoV-2. Viruses). In the present study data from April to September was missing.  Obtaining the missing data would significantly help to improve the article and the difference in the epidemiology of the virus. Otherwise, it has to explain in limitations. I do not believe that in the missing period were no cases of HRSV and/or acute bronchiolitis.

 

2.      The second in the result section HRSV prevalence is divided into three groups: before the pandemic, the pandemic, and after the pandemic. If you keep this division then you need to unify it also in the Material and Methods section. It is known that SARS-CoV-2 positive cases were still lasting after September 2021, there were a lot of positive cases till May 2022. Therefore, I think that the division of these three groups in point of HRSV is not suitable. It will be better if the authors divided patients before the SARS-CoV-2 pandemic, during and after measures started, and after being lifted.

 

3.      Page 2 line 90: add median age and IQR. Why did the authors decide to include only children under one year of age? Diagnosis of acute bronchiolitis is diagnosed in children up to 2 years of age. This decision should to explained in the discussion section or as a limitation because can be also the cause of a low number of acute bronchiolitis.

 

4.      Page 3 line 131 in the results section: Give the total number of children with acute bronchiolitis from September 2017 to March 2023 that were hospitalized in the included Pediatric Departments.

 

5.      On Page 3 line 120 in the material and methods section laboratory methods are missing. Also, data about co-infection with other microbiological agents is missing in the Results section, although the authors state in line 103.

Minor points:

1.     Change RSV to HRSV (Human respiratory syncytial virus).

2.     Figures 1, 3, and 4 have poor resolution. Improve the resolution.

3.     Table 4: add a research group in each column of the table.

4.     Figure 2: add an explanation of Figure 2 (green and blue line).

5.     Page 7 line 13: change Table 4 to Table 5. There are discrepancies between the number of table reported in the text and the table name.

6.     On page 1 line 18, 19, and 21 in the abstract section correct “analyse” to analyze.

7.     On page 2 line 48 change “defence” to defense.

8.     On page 2 line 54 change “delaying” to delayed.

9.     On page 2 line 68 delete was.

10.  On page 3 line 114 change “analysed” to analyzed.

11.  On page 3 line 117 change “in accordance with” to following current legislation.

12.  On page 5 line 175 change “statistically” to statistical.

13.  On page 6 line 187 change “x ray” to X-ray.

14.  On page 9 line 280 change “reduction in pollution” to pollution reduction.

 

15.  On page 9 line 283 change “hypothesis” to hypotheses. 

Author Response

Dear Reviewer,

We would like to thank you so much for your precious work. We appreciate the points that you have highlighted. We modified the text according to your suggestions (corrections are underlined in the manuscript).

I upload the file with a point-by-point response. Please see the attachment. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Editor 

many thanks for asking me to review this original article aimed to: 1. analyse the temporal trend of RSV in the three periods; 2.analyse the epidemiological characteristics to highlight clinical differences in the patients affected, in the severity of the infections and in the short-term outcomes; and, lastly, 3. to analyse the RSV prevalence in the global bronchiolitis hospitalization in the same over reported periods.

The paper is interesting and worthy of publication. No issues have been detected regarding the quality of the presentation and the content.

I only suggest comparing the author's data with other national findings reflecting the status in other countries of Italy. It could be interesting to compare the epidemiologic data of northern Italy with the data of middle and southern Italy. Please, refer to the following recent papers focusing on this issue: Presti S, et al. Viruses. 2023 Aug 28;15(9):1825. doi: 10.3390/v15091825. 

Manti S, et al. Children (Basel). 2022 Nov 9;9(11):1723. doi: 10.3390/children9111723.

Comments on the Quality of English Language

Minor editing of English language required

Author Response

Dear Reviewer,

We would like to thank you so much for your precious work. We appreciate the points that you have highlighted. We modified the text according to your suggestions (corrections are underlined in the manuscript).

We upload a point-by-point response. Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Nice study confirming the impact of COVID-19 restrictions on the epidemiology of RSV.

- just need to add some details of the laboratory diagnostic protocols and tests used in the 3 Spoke hospitals for RSV from their data sources, as this can bias the results slightly in terms of tests sensitivity/specificity.

 

 

Author Response

Dear Reviewer,

We would like to thank you so much for your precious work. We appreciate the points that you have highlighted. We modified the text according to your suggestions (corrections are underlined in the manuscript).

We upload a point-by-point response. Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

 

I would like to thank you for writing a very interesting article. I have only a few additional suggestions.

 

1.    The change in name from RSV to HRSV is needed, because of the new guidelines in virus nomenclature. At that point the title of the article should be changed from “Impact of SARS-CoV2 pandemic and lockdown on the RSV circulation: experience of three spoke hospitals in northern Italy” to Impact of SARS-CoV2 pandemic and lockdown on the HRSV circulation: experience of three spoke hospitals in northern Italy.

2.    Namely, given that the antigen determination method has been used, this shortcoming needs to be described (line 388), because rapid antigen tests are less specific and sensitive than molecular methods. It would help if you discussed this. The sentence in the Study Design section line 112 should be changed ….The test used to detect the RSV was a rapid antigen test…Because rapid tests are also molecular tests and this is essential data.

 

3.    In the case of co-infections, it is necessary to write which pathogens were looked at and with what methods, and not only the results of coinfection. Add explanation in Material and Methods section (line 131). 

Author Response

Dear Reviewer,

We would like to thank you so much for your precious work. We accepted all your suggestions. 

We modified the text according to your suggestions (corrections are underlined in the manuscript).

• We change RSV in HRSV

 

• Concerning the test for HRSV: 

The test used to detect the HRSV was a rapid antigen test for the qualitative detection in nasopharyngeal swabs; the test used in our hospitals is the same from the 2012 (BinaxNOW HRSV CARD –Abbot). The main strength of our study is that it is performed in three Spoke hospitals which are part of the same health district (ASL); therefore, clinicians have the same devices for the treatment of respiratory failure and the same tests to detect HRSV. The test used is an antigen test that is less sensitive and specific than molecular methods but it has been the same in the three hospitals and in the different periods analyzed.  

• Concerning the co-infections: 

The coinfection has been investigated based on clinical suspicion: usually, we do antibodies on blood samples for Epstein Bar Virus or Mycoplasma pneumonia. In Group B all patients were tested for SARS-CoV2 with an antigen rapid test on a nasal swab for hospital admission.