The Impact of the COVID-19 Pandemic on the Clinical Course of Influenza in Hospitalised Children in the Years 2017–2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript addresses a timely and clinically relevant topic: the impact of the COVID-19 pandemic on the clinical course of influenza in hospitalized children. The long observation period (2017–2025) and relatively large pediatric cohort strengthen the descriptive value of the study. The objectives are clearly stated, and the manuscript is generally well organized. Overall, the study contributes meaningful post-pandemic insights to a field where data remain limited.

However, several methodological and interpretative issues should be addressed before the manuscript can be considered for publication

1. The retrospective, single-center design inherently limits generalizability and should be emphasized more clearly as a major limitation. Importantly, during part of the pandemic period (April 2020–September 2021), the study center did not admit non-COVID patients. This may introduce a substantial selection bias, potentially enriching the pandemic group with more severe or atypical cases. This issue requires deeper discussion.

2. All comparisons are based on univariate analyses. A multivariable model (e.g., logistic regression) adjusting for age, sex, and influenza virus type (A vs. B) would be valuable to determine whether the post-pandemic period independently predicts a higher risk of complications.

3. Some conclusions imply a causal relationship between the pandemic (or immunity debt) and increased complication rates. Given the observational nature of the study, these interpretations should be phrased more cautiously and framed as hypotheses rather than causal inferences.

4. The finding that none of the hospitalized children were vaccinated against influenza is striking. This warrants further discussion, particularly regarding local vaccination policies, potential reporting bias, and the impact on external validity.

5. Table 3 could be simplified to improve readability.

6. Although Bonferroni correction is mentioned, it is not always clear which comparisons were adjusted. This should be clarified in the Methods section.

7. Certain sections of the Discussion are repetitive and could be streamlined without losing scientific content.

Author Response

We would like to thank the Reviewer for the careful reading of our manuscript and for the constructive and balanced assessment. We appreciate the positive evaluation of the study’s relevance, cohort size, and observation period, as well as the valuable suggestions that helped us improve the methodological transparency and interpretation of our findings. Below, we provide a point-by-point response to all comments.

General Comment

The manuscript addresses a timely and clinically relevant topic… Overall, the study contributes meaningful post-pandemic insights…

Response:
We sincerely thank the Reviewer for this encouraging assessment and for recognizing the clinical relevance and descriptive value of our study.

Comment 1: The retrospective, single-center design inherently limits generalizability… the study center did not admit non-COVID patients… potential selection bias… requires deeper discussion.

Response:

We fully agree with the Reviewer that the retrospective, single-center nature of the study limits generalizability. Moreover, the temporary reorganization of the hospital during pandemic-era period with resumed admissions (October 2021–May 2023) represents an important potential source of selection bias.

Revision made:

• The Limitations subsection of the Discussion has been expanded to explicitly emphasize the single-center, retrospective design as a major limitation.

• We added a detailed discussion explaining that the pandemic-period cohort may be enriched with more severe or atypical influenza cases due to restricted hospital admissions, potentially affecting the observed complication profile.

Comment 2:  All comparisons are based on univariate analyses. A multivariable model would be valuable…

Response:

We acknowledge that multivariable modeling could provide additional insights. However, due to the retrospective design, the discontinuous recruitment during the pandemic period, and limited subgroup sizes—particularly for specific complications—performing a reliable multivariable logistic regression could lead to model instability and overfitting.

Revision made:

• This methodological limitation has now been explicitly acknowledged in the Discussion, stating that the findings should be interpreted as exploratory and descriptive rather than confirmatory.

• We clarified that the observed associations should not be interpreted as independent predictors.

Comment 3: Some conclusions imply a causal relationship… should be phrased more cautiously.

Response:

We agree and thank the Reviewer for highlighting this important issue. The observational nature of the study does not allow causal inference.

Revision made:

• All statements implying causality have been revised and rephrased using cautious, hypothesis-generating language.

• References to “immunity debt” are now explicitly framed as a possible explanatory hypothesis rather than a demonstrated mechanism.

Comment 4: The finding that none of the hospitalized children were vaccinated is striking and warrants further discussion.

Response:

We agree that this is an important and noteworthy observation.

Revision made:

• A dedicated paragraph has been added to the Discussion addressing local influenza vaccination policies, low vaccine uptake in the pediatric population in Poland, and the possibility of incomplete documentation in retrospective records.

• We also commented on the potential impact of this finding on external validity and generalizability.

Comment 5: Table 3 could be simplified.

Response:

We thank the Reviewer for this practical suggestion.

Revision made:

• Table 3 has been simplified by improving layout clarity and reducing redundancy, while preserving all clinically relevant information.

Comment 6: It is not always clear which comparisons were adjusted.

Response:

We agree that this required clarification.

Revision made:

• The Statistical Analysis section now explicitly states that Bonferroni correction was applied to all pairwise comparisons between Groups A, B, and C.

Comment 7: Certain sections of the Discussion are repetitive.

Response:

We appreciate this observation.

Revision made:

• The Discussion has been streamlined to reduce redundancy, improve flow, and enhance clarity without loss of scientific content.

We sincerely thank the Reviewer for the insightful and constructive comments, which significantly improved the clarity, methodological transparency, and interpretative rigor of the manuscript. We believe that the revised version adequately addresses all concerns and strengthens the overall quality of the study.

All revisions were implemented consistently across the manuscript to ensure methodological coherence.

Yours faithfully, 

Zuzanna Wasielewska

Reviewer 2 Report

Comments and Suggestions for Authors

This retrospective single-center study examining influenza complications in hospitalized Polish children across pre-pandemic, pandemic, and post-pandemic periods addresses a clinically relevant question with important public health implications. The manuscript is well-structured and presents findings that contribute to our understanding of how COVID-19 control measures may have influenced influenza epidemiology and clinical presentation in pediatric populations. However, several methodological and interpretive concerns require attention before publication can be recommended:

1. The authors define Group B (pandemic period) as April 2020 to May 2023, yet acknowledge that their center was dedicated exclusively to COVID-19 patients from April 2020 to September 2021, during which no influenza patients were admitted. This 18-month gap creates a substantial temporal discontinuity within Group B, effectively making it represent only October 2021 to May 2023. This condensed timeframe may not adequately capture pandemic-era influenza patterns and introduces potential selection bias, as the reduced sample size in Group B (n=120) compared to Groups A (n=223) and C (n=210) may reflect both genuine epidemiological changes and institutional case mix alterations. The authors should either explicitly exclude the April 2020-September 2021 period from Group B or provide detailed justification for its inclusion, along with sensitivity analyses examining whether the 18-month gap materially affects their conclusions.

2. The manuscript lacks a priori sample size calculations or post-hoc power analyses. Given the unequal group sizes and the number of comparisons performed across multiple outcomes (complications, laboratory parameters, age subgroups), readers cannot assess whether negative findings represent true null effects or insufficient statistical power. The higher complication rate in Group C versus Group A reached statistical significance (p=0.02), yet the comparison between Groups A and B (52.91% versus 63.33%, p=0.07) approached significance despite a smaller sample in Group B. Power analysis would clarify whether this represents a genuine trend or a Type II error. Additionally, the multiple age-stratified analyses of CRP and PCT elevations (Figure 1) were not adjusted for multiple testing, potentially inflating Type I error rates.

3. The dramatic shift in influenza type distribution across groups represents a critical confounding variable that undermines causal attribution to pandemic effects. Group B exhibited a markedly different viral ecology compared to Groups A and C, with influenza B comprising 43.33% of cases versus 10.76% in Group A and 24.29% in Group C. The authors acknowledge that influenza B was associated with increased myositis frequency (citing Agyeman et al.'s finding of 76% influenza B attribution), yet they do not adequately address how this type distribution might independently explain many observed differences in complication profiles. The higher myositis rate in Group B (13.33% versus 0.90% in Group A) could reflect viral subtype rather than pandemic-related immunity debt. Similarly, the lower pneumonia rate in Group B might be influenced by influenza B's different pathogenic profile rather than solely by social distancing measures. The authors should perform stratified analyses comparing outcomes within influenza A and influenza B subgroups separately across the three time periods, or employ multivariable regression models that adjust for viral type when examining temporal trends in complications.

4. The authors invoke the "immunity debt" concept to explain increased post-pandemic complications, citing Cohen et al.'s theoretical framework. However, this explanation remains speculative in the context of influenza, which has different immunological dynamics compared to RSV or other respiratory viruses more directly affected by reduced exposure. The immunity debt hypothesis would predict that children with no prior influenza exposure should experience more severe disease, yet the manuscript provides no data on individual patient exposure history, prior influenza infections, or infection-naïve status. Furthermore, alternative explanations deserve consideration. Healthcare-seeking behavior may have changed post-pandemic, with lower thresholds for hospitalization reflecting parental anxiety or altered triage patterns. The observed increase in gastrointestinal symptoms in Group C (23.81% versus 17.49% in Group A) might reflect changing clinical documentation practices rather than true epidemiological shifts. The manuscript shall be strengthened by (1) presenting data on length of stay, admission criteria, or illness severity at presentation to assess whether case mix changed, (2) discussing competing hypotheses such as healthcare system strain, changed antimicrobial prescribing patterns, or viral evolution, and (3) acknowledging the limitations of retrospectively applying the immunity debt framework without direct immunological measurements.

5. The laboratory data presentation suffers from interpretive ambiguity. The authors report median CRP values of 6.25-6.3 mg/dL across all groups with no significant differences, stating these are "slightly above the upper limit of normal (N <5 mg/dL)." However, the interquartile ranges (1.45-20.6 mg/dL) indicate substantial within-group variation. More importantly, the clinical significance of analyzing both median values and extreme values (CRP >60 mg/dL, PCT >2 ng/mL) requires clarification. The dichotomization at these high thresholds appears arbitrary without clear clinical or prognostic justification. What proportion of children with CRP >60 mg/dL or PCT >2 ng/mL actually had bacterial co-infections confirmed by culture? Were antibiotic prescribing rates different across groups? The observation that elevated CRP and PCT did not overlap across age groups (paragraph 307) is presented without interpretation. Does this suggest different pathophysiological processes, or does it reflect small sample sizes in the stratified analyses? The authors should either provide receiver operating characteristic analyses demonstrating optimal cut-points for these markers in predicting bacterial co-infection, or acknowledge that the chosen thresholds lack validation in this context.

6. The statement that "none of the hospitalised patients had been vaccinated against influenza during the infectious season in which they were hospitalised" (lines 112-114) is remarkable yet inadequately discussed. This represents a missed opportunity to contextualize findings within Poland's vaccination landscape and to strengthen public health recommendations. Did vaccination rates in the general pediatric population differ across the three study periods? The post-pandemic period might have seen increased vaccine hesitancy or, conversely, heightened awareness of respiratory virus prevention. Without population-level vaccination data, readers cannot determine whether the hospitalized cohort is representative of unvaccinated children specifically or of the general pediatric population. This limitation deserves explicit acknowledgment in the discussion, and the complete absence of vaccinated children from the hospitalized cohort itself provides indirect evidence of vaccine effectiveness that warrants mention.

7. Several methodological details require specification. (1) The pneumonia diagnosis "based on radiological findings or abnormal auscultatory signs" (lines 92-93) appears to allow clinical diagnosis without radiographic confirmation, which may introduce diagnostic variability across the eight-year study period as chest radiography practices evolved. Were standardized radiographic criteria applied? (2) The myositis definition requires elevated CPK plus symptoms, but threshold values for CPK elevation are not provided. (3) The neutropenia severity categories (mild, moderate, severe) are defined by absolute neutrophil counts, yet the text does not clarify whether these represent age-adjusted thresholds, which vary considerably between infants and adolescents. (4) The statistical methods mention using the Mann-Whitney U test for group comparisons, yet three groups are being compared, for which the Kruskal-Wallis test would be more appropriate, followed by post-hoc pairwise comparisons.

8. Table 2 presents complication data with p-values for three pairwise comparisons (A vs. B, A vs. C, B vs. C), yet the text selectively reports only statistically significant findings, omitting discussion of several null results that might be informative. For example, SIRS rates declined numerically from 11.66% to 6.67% across groups but without statistical significance. Is this a clinically meaningful trend that lacked power to detect, or truly a null finding? The reporting of "any complication" at the top of Table 2 (59.49% overall) does not clearly indicate whether this represents children with at least one complication, or whether children with multiple complications are counted separately. The text states that in Group C, 64.29% had complications, yet the sum of individual complication percentages exceeds this figure, confirming that many children had multiple complications. A supplementary table presenting the distribution of complication number (0, 1, 2, 3+ complications per patient) would enhance interpretability.

9. The discussion appropriately situates findings within existing Polish literature (Wrotek et al., Siewert et al.) and international studies (Bennet et al., Lin et al.), yet it would benefit from integration of the three suggested references provided with this review. (1) Kiefer et al. (2025) demonstrated anticyclical patterns between RSV hospitalization waves and SARS-CoV-2 circulation in Eastern Bavaria, providing direct mechanistic evidence for viral interference that parallels the authors' observations for influenza (https://doi.org/10.3390/v17121584). This reference would strengthen the discussion of reduced pneumonia during the pandemic period. (2) Şık et al. (2025) identified distinct clinical phenotypes of severe pediatric influenza in post-COVID Turkey, with influenza B showing disproportionate neurological complications and influenza A/RSV co-infections driving respiratory failure (https://doi.org/10.3390/children13010014). These findings directly support the current manuscript's observations about influenza type-specific complication profiles and deserve citation in the myositis discussion. (3) Raycheva et al. (2025) systematically reviewed economic evidence for COVID-19 interventions, finding that combined strategies (vaccination, testing, social distancing) were most cost-effective (https://doi.org/10.3390/healthcare13243249). This provides health economics context for the public health measures implemented during the pandemic period and could inform the manuscript's conclusions about preventive strategies.

10. The manuscript lacks a dedicated limitations section, which should be added to acknowledge: (1) single-center design limiting generalizability, (2) retrospective data collection with potential for incomplete documentation, (3) absence of viral load measurements or sequencing data to assess whether viral variants contributed to changing severity, (4) lack of data on antiviral treatment timing (early versus late oseltamivir initiation) which might confound complication rates, (5) inability to capture outpatient influenza cases or those managed in emergency departments without admission, potentially biasing toward more severe presentations, and (6) the 18-month institutional gap in Group B creating temporal discontinuity.

11.  Figure 1 requires revision for clarity. The bar charts showing age distribution of elevated CRP and PCT levels use small sample sizes (n=1-9 per category), making visual interpretation difficult. Error bars or confidence intervals should be added if feasible, or the authors should consider presenting these data in tabular rather than graphical format. The figure legend should specify absolute numbers rather than requiring readers to extract these from the bars. Table 1 could be enhanced by adding a column for overall totals and p-values comparing sex distribution and viral type distribution across groups, as these represent potential confounders that deserve statistical testing.

11.  The manuscript is generally well-written with only minor language issues. (1) Line 39: "high costs in Poland" should specify whether this refers to direct medical costs, societal costs, or productivity losses. (2) Line 72: The phrase "remaining in force until May 2022" could be clarified as "formally lifted in May 2022." (3) Line 242: "immunity debt" should be placed in quotation marks on first use to indicate this is an emerging concept rather than established nomenclature. (4) The conclusion states that "social isolation... limited the spread of SARS-CoV-2 infection but also reduced the transmission of other respiratory pathogens" (lines 317-320). This assertion is supported by the data for pneumonia reduction during the pandemic, yet the manuscript simultaneously argues that post-pandemic complications increased, suggesting delayed rather than prevented infections. This apparent contradiction requires reconciliation.

Given my comments  I recommend major revisions before the manuscript can be considered for publication.

Author Response

We would like to thank the Reviewer for the thorough, detailed, and constructive evaluation of our manuscript. We appreciate the recognition of the clinical relevance of the study and the extensive comments, which have helped us to improve the methodological clarity, interpretative balance, and transparency of the manuscript. Below, we address each comment point by point.

Comment 1: The pandemic group includes an 18-month gap during which no influenza patients were admitted. This creates temporal discontinuity and potential selection bias.

Response:

We fully agree with the Reviewer that the 18-month period during which the study centre admitted exclusively COVID-19 patients represents a major methodological consideration.

Revision made:

To avoid temporal dilution and misclassification, we revised the definition of Group B. The pandemic group now explicitly represents October 2021 to May 2023, corresponding to the period of resumed non-COVID admissions during the pandemic era. This clarification has been incorporated into the Materials and Methods section and further discussed as a limitation.

Comment 2:  The lack of power analysis and multiple comparisons limits interpretability of negative findings.

Response:

We acknowledge this limitation. Due to the retrospective nature of the study, no a priori sample size calculation was performed, and group sizes were determined by case availability within predefined periods.

Revision made:

A dedicated paragraph has been added to the Discussion clarifying that the study may be underpowered to detect small-to-moderate differences, particularly in Group B, and that non-significant findings should be interpreted cautiously. Age-stratified and multiple comparisons are now explicitly described as descriptive, with acknowledgment of potential type I and type II errors.

Comment 3: The marked shift in influenza type distribution undermines causal attribution to pandemic effects.

Response:

We agree that influenza virus type represents a critical confounding factor.

Revision made:

The Discussion has been expanded to emphasize that the increased proportion of influenza B infections during the pandemic period may independently explain observed differences in complication profiles, including increased myositis and reduced pneumonia rates. We explicitly state that stratified or multivariable analyses adjusting for virus type were not feasible due to limited subgroup sizes and that this limits causal inference.

Comment 4: The immunity debt hypothesis remains speculative and alternative explanations should be discussed.

Response:

We fully agree.

Revision made:

All references to “immunity debt” have been rephrased using cautious, hypothesis-generating language. We explicitly acknowledge the lack of individual immunological or exposure data and discuss alternative explanations, including changes in healthcare-seeking behaviour, admission thresholds, documentation practices, and viral evolution.

Comment 5: The clinical significance of CRP and PCT thresholds and dichotomization requires clarification.

Response:

We acknowledge that the selected CRP and PCT thresholds represent clinical rather than validated prognostic cut-offs.

Revision made:

The Discussion now clarifies that median values and dichotomized analyses were intended for descriptive comparison only. We explicitly acknowledge the lack of systematic microbiological confirmation of bacterial co-infection and antibiotic prescribing data, and state that the chosen thresholds should not be interpreted as diagnostic indicators.

Comment 6: The absence of vaccinated children is remarkable and insufficiently discussed.

Response:

We agree and appreciate this observation.

Revision made:

The Discussion has been expanded to contextualize this finding within historically low pediatric influenza vaccination coverage in Poland. We acknowledge the absence of population-level vaccination data and potential documentation bias, while noting that the complete lack of vaccinated children among hospitalized cases indirectly supports the protective role of vaccination.

Comment 7: (1) Pneumonia diagnosis criteria, (2) CPK thresholds for myositis, (3) age adjustment for neutropenia, (4) statistical test selection.

Response:

We thank the Reviewer for highlighting these important methodological details.

Revision made:

• Pneumonia diagnosis criteria were clarified to reflect real-world clinical practice when radiographic confirmation was unavailable.

• Elevated CPK was defined as exceeding age-adjusted upper reference limits.

• Neutropenia was classified using fixed absolute neutrophil count thresholds (mild, moderate, severe), applied uniformly to all patients. Although age-adjusted reference ranges may provide greater physiological precision, retrospective reclassification according to age-specific norms was not feasible. Neutropenia was therefore analysed comparatively between study groups rather than as an absolute prevalence estimate.

• The Statistical Analysis section now explicitly states that Mann–Whitney U tests were used for pairwise comparisons with Bonferroni correction, rather than for global three-group testing.

Comment 8: Clarification of “any complication” and discussion of null findings is needed.

Response:

We agree.

Revision made:

The Results section now clarifies that “any complication” refers to the presence of at least one complication per patient and that multiple complications could co-occur. The Discussion acknowledges numerical trends that did not reach statistical significance (e.g., SIRS) and interprets them cautiously as potentially underpowered findings rather than definitive null effects.

Comment 9: The discussion would benefit from integration of the suggested references.

Response:

We thank the Reviewer for these valuable suggestions.

Revision made:

The Discussion has been expanded to incorporate the cited studies on viral interference, influenza subtype–specific complication profiles, and the broader public health impact of COVID-19 interventions, strengthening the contextual interpretation of our findings.

Comment 10: Lack of a dedicated limitations section

Response:

We agree.

Revision made:

A dedicated Limitations section has been added, explicitly addressing the single-center design, retrospective data collection, lack of viral sequencing and antiviral timing data, exclusion of non-hospitalized cases, and the temporal discontinuity within the pandemic period.

Comment 11: Figures, tables, and minor language issues

Response:

We appreciate these detailed suggestions.

Revision made:

• Figure 1 has been revised for clarity, with explicit acknowledgment of small subgroup sizes and descriptive intent.

• Table 1 and Table 3 were refined to improve readability and highlight potential confounders.

• Minor language revisions were implemented, including clarification of cost definitions, terminology precision, and consistent use of quotation marks for emerging concepts.

Final Statement

We sincerely thank the Reviewer for the comprehensive and insightful critique. We believe that the revisions made have substantially strengthened the methodological transparency, interpretative rigor, and clinical relevance of the manuscript. We hope that the revised version adequately addresses all concerns and meets the standards for publication.

All revisions were implemented consistently across the manuscript to ensure methodological coherence.

Yours faithfully,

Zuzanna Wasielewska

Reviewer 3 Report

Comments and Suggestions for Authors

Introduction 
Comment1: In lines 72–73, the phrase “The ‘end’ of the global pandemic…” is not scientifically/institutionally accurate. On May 5, 2023, the WHO announced that COVID-19 is no longer a PHEIC (end of a public health emergency of international concern), which is a downgrade in the level of international alert/management and does not explicitly state that “the global pandemic has ended.”
It is proposed to rephrase it to reflect the actual event (end of PHEIC / end of emergency phase) and to avoid the term “end of the global pandemic,” because it is misleading.

Materials and Methods

Comment 2: Regarding Group B, the manuscript states that from April 2020 to September 2021 the study centre admitted patients with COVID-19 only. Please clarify explicitly which sub-interval the Group B influenza cases come from and comment on the possible impact of this discontinuity/selection on the comparability of the groups and the interpretation of the findings.

Comment 3: I would like a clarification regarding the phrase "The non-parametric Mann–Whitney U test was used to compare groups", as the Mann–Whitney U involves comparing two independent groups, whereas in the study there are three groups (A, B, C).

Comment 4:  Please provide more/clearer explanations for the myositis finding, both in the Discussion and in the Conclusions. The increased frequency in Group B seems to coexist with a significant change in the distribution of the virus type (especially a higher proportion of influenza B in Group B), which may act as a confounding factor. It would be useful to clarify whether the finding is mainly attributable to the “pandemic period” or to the virus type (and/or age).

Conclusions

Comment 5: The Conclusions section is relatively extensive and reproduces elements of the Discussion/Results. I would suggest that it be made more condensed, with a clear formulation of the 2–4 key take-home messages, avoiding repetition and generalizations that do not arise directly from the data. Please revise accordingly.

 

Author Response

We would like to thank the Reviewer for the thorough and constructive evaluation of our manuscript.

We greatly appreciate the insightful comments, which have helped us to improve the clarity, methodological transparency, and scientific accuracy of the manuscript. All comments have been carefully considered, and the manuscript has been revised accordingly. Below, we provide a point-by-point response to each comment. Changes made in the manuscript are indicated in the revised version.

Introduction - Comment 1

In lines 72–73, the phrase “The ‘end’ of the global pandemic…” is not scientifically/institutionally accurate. On May 5, 2023, the WHO announced that COVID-19 is no longer a PHEIC, which does not explicitly state that “the global pandemic has ended.” It is proposed to rephrase it accordingly.

Response: We fully agree with the Reviewer and appreciate this important clarification. The wording in the Introduction has been revised to accurately reflect the World Health Organization’s announcement and to avoid implying a formal end of the global pandemic.

Materials and Methods

Comment 2

Regarding Group B, please clarify explicitly which sub-interval the Group B influenza cases come from and comment on the possible impact of this discontinuity/selection on the comparability of the groups and interpretation of the findings.

Response: We thank the Reviewer for highlighting this important methodological issue. We have clarified that influenza cases in Group B originated exclusively from periods within pandemic-era period with resumed admissions (October 2021–May 2023) when the study centre resumed admission of non-COVID-19 patients.

Revision made:

• A clarifying sentence has been added to the Materials and Methods section specifying the discontinuous nature of patient recruitment in Group B.

• An additional comment has been included in the Discussion addressing the potential selection bias and its possible impact on group comparability and interpretation of the findings.

Comment 3

The Mann–Whitney U test compares two independent groups, whereas the study includes three groups (A, B, C). Please clarify.

Response: We agree with the Reviewer and thank them for pointing out the need for clarification. The statistical analysis involved pairwise comparisons between groups rather than a single comparison across three groups.

Revision made:

The Statistical Analysis section has been revised to explicitly state that the Mann–Whitney U test was applied for pairwise comparisons (A vs. B, A vs. C, and B vs. C), with Bonferroni correction used to adjust for multiple testing.

Comment 4

Please provide clearer explanations for the myositis finding. The increased frequency in Group B may be confounded by the higher proportion of influenza B infections. Clarify whether the finding is attributable to the pandemic period or virus type (and/or age).

Response: We appreciate this insightful comment. We have expanded the Discussion to explicitly address the potential confounding effect of influenza virus type. Our analysis indicates that the increased frequency of myositis coincides with a higher proportion of influenza B infections in Group B, which is consistent with previous literature.

Revision made:

• The Discussion section now includes a more detailed interpretation emphasizing that the increased incidence of myositis is more likely related to virus type rather than the pandemic period itself.

• The Conclusions have been revised to reflect this interpretation more cautiously, clearly distinguishing between temporal associations and potential confounding factors.

Conclusions

Comment 5

The Conclusions section is relatively extensive and reproduces elements of the Discussion/Results. Please condense it into 2–4 key take-home messages.

Response: We agree with the Reviewer and thank them for this suggestion. The Conclusions section has been substantially shortened and restructured. The revised Conclusions now focus on four concise, data-driven take-home messages, avoiding repetition and limiting interpretation strictly to findings supported by the results.

We sincerely thank the Reviewer for their valuable feedback, which has significantly strengthened the manuscript in terms of scientific rigor, clarity, and interpretability. We hope that the revised version satisfactorily addresses all comments and we remain at the Reviewer’s disposal for any further clarification.

All revisions were implemented consistently across the manuscript to ensure methodological coherence.

Yours faithfully, 

Zuzanna Wasielewska

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have demonstrated intellectual honesty by acknowledging the inherent limitations of their retrospective, single-center data. The manuscript now accurately reflects the descriptive nature of the findings and contributes valuable insights into the post-pandemic clinical landscape of pediatric influenza.

Author Response

We thank the Reviewer for this positive and thoughtful assessment of our work. We appreciate the recognition of our transparent discussion of the study’s limitations and its contribution to understanding the post-pandemic clinical landscape of pediatric influenza.

Reviewer 2 Report

Comments and Suggestions for Authors

The Raycheva et al. reference (cited as [29] on lines 405-407) does not appear in the reference list. Reference 29 in the list is "Piret J, Boivin G. Viral Interference between Respiratory Viruses" which is unrelated to the cost-effectiveness systematic review cited in the text. The authors need to either add the correct Raycheva reference or remove this citation.

Overall, the revision addresses substantive methodological concerns well. These are primarily copy-editing issues that should be resolved in a final proofread before resubmission.

Author Response

We thank the Reviewer for identifying this reference inconsistency. The incorrect reference to Piret and Boivin has been removed, and the appropriate article by Raycheva et al. has been added to the reference list and correctly cited in the text (lines 405–407). The reference list has been updated accordingly, and consistency between in-text citations and references has been carefully checked.

Yours faithfully,

Zuzanna Wasielewska