Review Reports - Comparative Epidemiological and Clinical Outcomes on COVID-19 and Seasonal Influenza Hospitalized Patients during 2023

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In the manuscript entitled “Comparative Epidemiological and Clinical Outcomes on Covid-19 and Seasonal Influenza Hospitalized Patients During 2023” Vlase and Colleagues described a different profile of infected individuals in Romania. They showed that flu-hospitalized patients are more likely to present fever, chills and rhinorrhea, while Covid-19 hospitalized patients were more likely to present clinical complications such as nephritis and hypercoagulation.

The manuscript is interesting and follows other works that focus on understanding the impact of Covid-19 on another respiratory virus infection. New evidence demonstrated that Covid-19-infected individuals present a different profile compared to other respiratory viruses. A growing body of evidence has shown that the circulation of SARS-CoV-2 has changed the symptom and clinical profile of Flu infections and changed the epidemiology of the infection.

I have some comments regarding the flow of ideas, the literature review, and especially the analysis and interpretation of the results. Please, see the comments below.

Major comments:

1. The introduction is too short and superficial. The authors did not introduce the relevant literature on Covid-19 and Flu dynamics, epidemiological trends, differences in symptoms and studies that support the effect of Covid-19 on Flu dynamics. A robust introduction to flu before and after Covid-19 should also be provided.

2. The results were not properly interpreted. The authors must review the results carefully. They inform the existence of significance where this does not exist or indicate that significance doesn’t exist when the result is significant.

Minor comments:

3. There are numerous typographical errors in the manuscript. Please review carefully.

4. Line 41: “(…) antigenic variations that occur at specific intervals”. Please be more specific to avoid misunderstanding.

5. Lines 76-83: Some statistical descriptions are missing in the Material and Method section. The authors used the Chi-Squared test and Kruskal Wallis test, but they are not mentioned in the section, only Fisher Exact test and Mann-Whitney. A one-tailed or two-tailed test was used?

6. Line 83: “A p-value <0.01 was considered statistically significant”. However, at some points in the manuscript, the authors considered results with p > 0.01 significant.

7. Line 105-106: There are differences in education and occupation between the virus in Table 1.

8. Table 1: Why did the authors not calculate the odds ratio for Table 1?

9. Lines 112-113 and Table 2: This statement is incorrect. There is no significance for the comorbidities. Only hypertension, CVA and DM present significant differences.

10. Line 123: “(…) may have a higher predictive value (…)”. I suggest that the authors indicate that influenza individuals are more likely to present these symptoms and inform the respective odds ratio value in the text.

11. Lines 144-146: This statement is very confusing. The use of antibiotics indicates a higher suspicion of viral infection?????? Additionally, where is this result in the tables?

12. Lines 153-154: “(…) diarrhoea was associated in 9 patients.”. Was not “associated”, was “present”. The association needs a type of statistical analysis.

13. Lines 13: 165-166 and Table 4: “diarrhoea with Clostridioides difficile were more associated with Covid-19 (Table 4)”. Diarrhoea was not significant. Remember that you chose a p < 0.01 for statistical significance.

14. Table 4: “Cl. difficile” in italic form.

15. Discussion: a comparative analysis/description regarding Covid-19 and influenza before and after the Covid-19 pandemic is missing.

Author Response

Dear Reviewer,

Thank you for your valuable observations. We hope thar our revised manuscript to be substantially improved according to the publication standards.

Comments and Suggestions for Authors

I have some comments regarding the flow of ideas, the literature review, and especially the analysis and interpretation of the results. Please, see the comments below.

Major comments:

The introduction is too short and superficial. The authors did not introduce the relevant literature on Covid-19 and Flu dynamics, epidemiological trends, differences in symptoms and studies that support the effect of Covid-19 on Flu dynamics. A robust introduction to flu before and after Covid-19 should also be provided.

A1: We have revised the introduction and supplemental data on Covid-19 and Flu dynamics, epidemiological trends, based on additional references:

Groves HE, Piché-Renaud PP, Peci A, Farrar DS, Buckrell S, Bancej C, Sevenhuysen C, Campigotto A, Gubbay JB, Morris SK. The impact of the COVID-19 pandemic on influenza, respiratory syncytial virus, and other seasonal respiratory virus circulation in Canada: A population-based study. Lancet Reg Health Am. 2021 Sep;1:100015. doi: 10.1016/j.lana.2021.100015. Epub 2021 Jul 17. PMID: 34386788; PMCID: PMC8285668.

Wang Q, Jia M, Jiang M, Liu W, Yang J, Dai P, Sun Y, Qian J, Yang W, Feng L. Seesaw Effect Between COVID-19 and Influenza From 2020 to 2023 in World Health Organization Regions: Correlation Analysis. JMIR Public Health Surveill. 2023 Jun 12;9:e44970. doi: 10.2196/44970. PMID: 37191650; PMCID: PMC10263104.

Yang J, Gong Y, Zhang C, Sun J, Wong G, Shi W, Liu W, Gao GF, Bi Y. Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges. Innovation (Camb). 2022 Sep 13;3(5):100306. doi: 10.1016/j.xinn.2022.100306. Epub 2022 Aug 17. PMID: 35992368; PMCID: PMC9384331.

Yewdell JW. Antigenic drift: Understanding COVID-19. Immunity. 2021 Dec 14;54(12):2681-2687. doi: 10.1016/j.immuni.2021.11.016. PMID: 34910934; PMCID: PMC8669911.

The results were not properly interpreted. The authors must review the results carefully. They inform the existence of significance where this does not exist or indicate that significance doesn’t exist when the result is significant.

A2: We revised the results, and we corrected the errors.

Minor comments:

There are numerous typographical errors in the manuscript. Please review carefully.

A3: We revised the typographical errors, but English language will be revised by a native English Editor.

Line 41: “(…) antigenic variations that occur at specific intervals”. Please be more specific to avoid misunderstanding.

A4: We revised.

Lines 76-83: Some statistical descriptions are missing in the Material and Method section. The authors used the Chi-Squared test and Kruskal Wallis test, but they are not mentioned in the section, only Fisher Exact test and Mann-Whitney. A one-tailed or two-tailed test was used?

A5: We revised the methodology and added the Chi-squared test. We replaced errored transcription of Kruskall-Wallis by Mann-Whitney test in the results section (3.2).

Line 83: “A p-value <0.01 was considered statistically significant”. However, at some points in the manuscript, the authors considered results with p > 0.01 significant.

A6: We revised the error in results section (3.7).

Line 105-106: There are differences in education and occupation between the virus in Table 1.

A7: We revised the results of demographic characteristics.

Table 1: Why did the authors not calculate the odds ratio for Table 1?

A8: We have revised the table by calculation Odds Ratio and Chi-square test of independence.

Lines 112-113 and Table 2: This statement is incorrect. There is no significance for the comorbidities. Only hypertension, CVA and DM present significant differences.

A9: We revised.

Line 123: “(…) may have a higher predictive value (…)”. I suggest that the authors indicate that influenza individuals are more likely to present these symptoms and inform the respective odds ratio value in the text.

A10: We revised the text.

Lines 144-146: This statement is very confusing. The use of antibiotics indicates a higher suspicion of viral infection?????? Additionally, where is this result in the tables?

A11: We revised the statement. We have not a table on antibiotic treatment. Just a single statistic analyse was used for the difference between antibiotic use prior hospitalization.

Lines 153-154: “(…) diarrhoea was associated in 9 patients.”. Was not “associated”, was “present”. The association needs a type of statistical analysis.

A12: We revised.

Lines 13: 165-166 and Table 4: “diarrhoea with Clostridioides difficile were more associated with Covid-19 (Table 4)”. Diarrhoea was not significant. Remember that you chose a p < 0.01 for statistical significance.

A13: We revised.

Table 4: “Cl. difficile” in italic form.

A 14: We have corrected.

Discussion: a comparative analysis/description regarding Covid-19 and influenza before and after the Covid-19 pandemic is missing.

A 15: We have completed the discussion section.

Monamele GC, Tsafack DT, Bilounga CN, Njankouo Ripa M, Nsangou Yogne C, Munshili Njifon HL, Nkom F, Tamoufe U, Esso L, Koro Koro F, Perraut R, Njouom R. The Detection of Influenza Virus Before and During the COVID-19 Pandemic in Cameroon. Influenza Other Respir Viruses. 2024 May;18(5):e13313. doi: 10.1111/irv.13313. PMID: 38757747; PMCID: PMC11099883.

Nowak MD, Sordillo EM, Gitman MR, Paniz Mondolfi AE. Coinfection in SARS-CoV-2 infected patients: Where are influenza virus and rhinovirus/enterovirus? J Med Virol. 2020;92:1699–700

Lampros A, Talla C, Diarra M, et al. Shifting Patterns of Influenza Circulation during the COVID-19 Pandemic, Senegal. Emerging Infectious Diseases. 2023;29(9):1808-1817. doi:10.3201/eid2909.230307.

Gandhi M. Post-viral sequelae of COVID-19 and influenza. Lancet Infect Dis. 2024 Mar;24(3):218-219. doi: 10.1016/S1473-3099(23)00762-4. Epub 2023 Dec 14. PMID: 38104584.

Kind regards,

Manuela Arbune

Answer to reviewer: 20 Aug 2024.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The article is generally well-written and is an interesting and informative read.

There are a few minor revisions suggested:

Title: epidemiological should start with lower case

Lines 18 and 19: I suggest removing ‘a’ before ‘priority’ and changing ‘concern’ to ‘concerns’

Line 20: I suggest removing the word ‘have’

Lines 30 and 31: can be rewritten to read ‘ COVID 19 and influenza have continued to cause numerous hospitalizations and a new strategy for efficient vaccinations is required’

Line 59: I suggest changing ‘for’ to ‘with’

Lines 94 – 98: can the percentages be written with decimal points and not commas please?

Lines 149 – 152: Bacteria strains were isolated from 6 influenza and 7 covid patients, making a total of 13 patients, but adding up the positive isolates gives us a total of 15, can this be better clarified?

Lines 217 and 218: people are vaccinated against influenza and covid, not vaccinated for. I suggest changing ‘for’ in both lines to ‘against’

Paragraph on lines 220 -224: It would be good to know how many paediatric patients had influenza

Line 227: ‘early years of the pandemic’ can be changed to ‘earlier in the pandemic’

Line 230: I suggest changing ‘since’ to ‘from’

Line 231: ‘founding’ should be changed to ‘finding’

Line 234: ‘et al’ not ‘& all’

Line 234 - 235: Please rewrite sentence for clarity

Line 242 – 243: what is meant by ‘and other studies’

Line 249 – 251: This paragraph can be deleted. It does not have much meaning and does not add any information to the article

Comments on the Quality of English Language

As highlighted above

Author Response

Dear reviewer,

Thank you for your valuable comments and suggestions.

We are grateful to you for your kindly provided academic remarks and we hope that our manuscript was improved substantially.

Comments and Suggestions for Authors

The article is generally well-written and is an interesting and informative read.

There are a few minor revisions suggested:

C1: Title: epidemiological should start with lower case

A1: We revised.

C2: Lines 18 and 19: I suggest removing ‘a’ before ‘priority’ and changing ‘concern’ to ‘concerns’

A2: We revised.

C3: Line 20: I suggest removing the word ‘have’

A3: We revised.

C4: Lines 30 and 31: can be rewritten to read ‘ COVID 19 and influenza have continued to cause numerous hospitalizations and a new strategy for efficient vaccinations is required’

A4: We revised.

C5: Line 59: I suggest changing ‘for’ to ‘with’

A5: We revised.

C6: Lines 94 – 98: can the percentages be written with decimal points and not commas please?

A6: We revised.

C7. Lines 149 – 152: Bacteria strains were isolated from 6 influenza and 7 covid patients, making a total of 13 patients, but adding up the positive isolates gives us a total of 15, can this be better clarified?

A7: We have supplementary explained that double bacterial isolates were found in 2 patients.

C8: Lines 217 and 218: people are vaccinated against influenza and covid, not vaccinated for. I suggest changing ‘for’ in both lines to ‘against’

A8: We revised.

C9: Paragraph on lines 220 -224: It would be good to know how many paediatric patients had influenza

A9: We have completed that 15.29% were paediatric patients under age 15 (26/270).

C10: Line 227: ‘early years of the pandemic’ can be changed to ‘earlier in the pandemic’

A10: We revised.

C11: Line 230: I suggest changing ‘since’ to ‘from’

A11: We revised.

C12: Line 231: ‘founding’ should be changed to ‘finding’

A12: We revised.

C13: Line 234: ‘et al’ not ‘& all’

A13: We revised.

C14: Line 234 - 235: Please rewrite sentence for clarity

A15: We have reformulated: “ Lehfeld AS & et all reported decreased loss rates altered sense of smell and taste rates decreasing from 23% and 24% during the Delta phase to 7% and 8% in the Omicron phase.”

C16: Line 242 – 243: what is meant by ‘and other studies’

A16: We replaced” and other studies” with “similar with other reports”.

C17: Line 249 – 251: This paragraph can be deleted. It does not have much meaning and does not add any information to the article

A17: We have deleted the paragraph.

Comments on the Quality of English Language

As highlighted above

A: An English Native Editor will revise the English Language.

Kind regards,

Manuela Arbune

Submission Date

03 July 2024

Date of this review

11 Aug 2024 05:19:26

Answer to reviewer

20 Aug 2024.

Author Response File: Author Response.pdf