Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors The manuscript is well written and presents clinically relevant findings. However, the following points should be addressed:

1. To improve readability, Table 1 should be condensed to fit on a single page where possible. If it must extend across multiple pages, the column headings should be repeated on each page.
2. With respect to the mortality, in lines 84–86, the authors report significantly higher mortality during the pandemic. Please clarify whether these deaths were directly attributable to infective endocarditis rather than other pandemic-related or comorbid factors. The potential contributions of delayed diagnosis, advanced disease at presentation, and perioperative or surgical complications should also be discussed.
3. Vegetation size and embolization  association shown in Figure 1C is clinically important and should be described and interpreted in greater detail in the Results section.
4. Do authors have any comparative data for pre pandemic IE outcomes from the same care center?

Author Response

1. To improve readability, Table 1 should be condensed to fit on a single page where possible. If it must extend across multiple pages, the column headings should be repeated on each page.

Response : Thank you for this suggestion. Table 1 has been reformatted and condensed with repeat column headings across pages, while preserving all variables, corrected denominators, percentages, p-values, and the explanatory legend. This improves readability.

2.With respect to the mortality, in lines 84–86, the authors report significantly higher mortality during the pandemic. Please clarify whether these deaths were directly attributable to infective endocarditis rather than other pandemic-related or comorbid factors. The potential contributions of delayed diagnosis, advanced disease at presentation, and perioperative or surgical complications should also be discussed.

Response: Thank you for this important comment. We reviewed the causes of death recorded in the medical records and confirmed that all in-hospital deaths were directly attributable to infective endocarditis or its immediate complications. No deaths were attributed to COVID-19 infection, other pandemic-specific causes, or unrelated comorbid conditions. We have clarified this point in the manuscript. Nevertheless, we acknowledge that pandemic-related factors may have indirectly influenced the clinical course by contributing to delayed presentation, delayed diagnosis, more advanced disease at admission, and potentially reduced or delayed access to specialised and surgical care. These factors are therefore discussed as possible contributors to disease severity and outcome rather than as direct causes of death.

3.Vegetation size and embolization  association shown in Figure 1C is clinically important and should be described and interpreted in greater detail in the Results section.

Response:Thank you for this important observation. We agree that the association between vegetation size and embolic events is clinically relevant. We have expanded the Results section to report the vegetation sizes in patients with and without embolic complications, including the corresponding median values, interquartile ranges, and p-value. We have also expanded the Discussion to emphasise the clinical relevance of this association and the potential contribution of greater vegetation burden to embolic risk.

4. Do authors have any comparative data for pre pandemic IE outcomes from the same care center?

Response:Thank you for this relevant question. Comparative patient-level data from the pre-pandemic period were not systematically collected as part of the present study. The study was specifically designed to compare patients with infective endocarditis admitted during the pandemic period (2020–2022) with those admitted during the post-pandemic period (2023–2025). Therefore, a directly comparable pre-pandemic cohort from our centre was not available for the present analysis. We agree that inclusion of a pre-pandemic reference period would provide valuable additional context for distinguishing pandemic-associated changes from longer-term temporal trends, and we have acknowledged this in the Limitations section.

Reviewer 2 Report

Comments and Suggestions for Authors

Here I find some problems.

1. Several percentages in Table 1 appear inconsistent with the reported sample sizes of the corresponding groups. Many percentages do not appear to be based on the reported group sample sizes (47 and 53). For example, “Male sex, n (%)”, 31 male patients, 31/47 is 66.0%, not 68.9%. Several percentages appear to have been calculated using denominators of 45 and 49 rather than the reported sample sizes of 47 and 53. The authors should clarify the reason for the missing observations and explain how these percentages were calculated.
2. In Table 1, “Surgery performed, n/N (%)”, p=1. Please check the p-value.
3. Reference 4 and 5 are the same. Please check whether reference 3 and 12 are related to the manuscript.
4. Line 26, the abstract reports embolic events of 62.3% versus 38.3%, with p = 0.028. Table 1 reports 63.3% versus 37.8%, with p = 0.023. Please check it.
5. Line 25, please delete “and survival improved from 48.9% to 75.5% (p = 0.007)”, which is redundant.
6. Inconsistent use of British and American English, such as centre/centre, aetiology/aetiology, and transoesophageal/transesophageal.
7. The authors should add a patient-selection flow diagram, including the number screened, reasons for exclusion, and final number included.

Author Response

1.Several percentages in Table 1 appear inconsistent with the reported sample sizes of the corresponding groups. Many percentages do not appear to be based on the reported group sample sizes (47 and 53). For example, “Male sex, n (%)”, 31 male patients, 31/47 is 66.0%, not 68.9%. Several percentages appear to have been calculated using denominators of 45 and 49 rather than the reported sample sizes of 47 and 53. The authors should clarify the reason for the missing observations and explain how these percentages were calculated.

Response 1: Thank you for this important observation. We have re-checked the entire database and recalculated all percentages using the final study cohort of 47 patients in the pandemic group and 53 patients in the post-pandemic group. The inconsistency identified in the previous version resulted from percentages that had inadvertently been calculated using an earlier version of the database, which did not yet include all patients in the final cohort.

All values in Table 1 have now been reviewed and corrected to ensure that the numerators, denominators, and percentages are consistent with the final dataset. Where data are missing for a specific variable, the corresponding available-case denominator is now explicitly reported as n/N (%), and this has been clarified in the table footnote. We appreciate the reviewer for identifying this issue, which helped us improve the accuracy and transparency of the manuscript.

2. In Table 1, “Surgery performed, n/N (%)”, p=1. Please check the p-value.

Response 2: All values in Table 1 have now been reviewed and corrected, p value for surgery performed is 0.322. All corections have been changed also in the text.

3. Reference 4 and 5 are the same. Please check whether reference 3 and 12 are related to the manuscript.

Response3:Thank you for identifying this duplication. References 4 and 5 referred to the same publication. The duplicate PubMed entry has been removed, the full journal citation has been retained, also referrences 3 and 12 were retained and the reference list and corresponding in-text citations have been renumbered accordingly.

4. Line 26, the abstract reports embolic events of 62.3% versus 38.3%, with p = 0.028. Table 1 reports 63.3% versus 37.8%, with p = 0.023. Please check it.

Response4: All values in Table 1 have now been reviewed and corrected, p value for embolism is 0.022. All corections have been changed also in the text.

5.Line 25, please delete “and survival improved from 48.9% to 75.5% (p = 0.007)”, which is redundant.

Response5:Line 25, the comment about survival was deleted.

6. Inconsistent use of British and American English, such as centre/centre, aetiology/aetiology, and transoesophageal/transesophageal.

Response 6: Thank you for noting the inconsistent use of British and American English. The manuscript has been carefully standardised throughout to British English. Terms such as “centre,” “aetiology,” “transoesophageal,” “specialised,” “recognised,” and “standardised” have been used consistently in the main text, tables, figure legends, and abbreviations.

7.The authors should add a patient-selection flow diagram, including the number screened, reasons for exclusion, and final number included.

Response7:Thank you for this suggestion. We have added a patient-selection flow diagram. All hospital admissions between January 2020 and December 2025 with an ICD code for endocarditis recorded as either a primary or secondary discharge diagnosis were screened (n = 120). After review of the medical records and application of the modified Duke criteria, 20 cases were excluded, leaving 100 patients with definite infective endocarditis for the final analysis. Of these, 47 were admitted during the pandemic period and 53 during the post-pandemic period. The screening and exclusion process has also been clarified in the Methods section.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors revised the manuscript in accordance with the review report.