SARS-CoV-2 Immunization Index in the Academic Community: A Retrospective Post-Vaccination Study
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis study provides important insights into the effectiveness of Covid-19 vaccines, focusing on Universities, which may have a large impact on the spread of infection. Therefore, it is basically considered worth publishing in this journal. However, the number of individuals in the observation group is not necessarily large to consider the impact on a national population. As a referee, I request additional explanation on the following points.
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The correlation between IgG and vaccine effectiveness, which is the premise of this study, should be carefully explained in the introduction. For example I found references below.
Earle, Kristen A., et al. "Evidence for antibody as a protective correlate for COVID-19 vaccines." Vaccine 39.32 (2021): 4423-4428.
Benkeser, David, et al. "Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial." Science translational medicine 15.692 (2023): eade9078.
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The relationship between the survey for recruiting volunteers and the recruits needs to be explained in detail. Were participants stratified to match the entire society? In the Discussion, the authors discuss the spread of infection in society in general and the effectiveness of vaccines, so they should emphasize that the target population reflects the structure of society as a whole.
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If the authors' aim is focused on academic populations, point 2 is not valid. In that case, after adding this to the explanation, the authors should state that the aim of this study is an academic population, and then state in the Discussion that the results of the volunteer group are appropriate for investigating the prevention of the spread of infection in academic populations.
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As the authors state, there has been discussion in previous studies about the correlation between in-person attendance at school and increased transmission of SARS-CoV-2 infection. In addition, many Universities have adopted remote classes to avoid the formation of groups. This is related to 2-3, but the authors should clarify whether the aim of their study is to focus on the effectiveness of vaccines in academic populations or in general society, where vaccination rates were particularly high, and then add a discussion in the Discussion according to the clarified purpose. An example is shown below.
If the aim is to affect society as a whole
Discussion on the extent to which the population size in this study can reflect the overall situation in Portuguese society.
If the aim is an academic population
Discussion on the effectiveness of the vaccine in academic populations by examining the age structure and vaccination rates in general academic populations through literature.
Author Response
Dear reviewer,
Authors are appreciative and acknowledge the reviewer criticism and hereby reply in concordance with the indicated comments in order to clarify and improve the manuscript.
This study provides important insights into the effectiveness of Covid-19 vaccines, focusing on universities, which may have a large impact on the spread of infection. Therefore, it is basically considered worth publishing in this journal. However, the number of individuals in the observation group is not necessarily large to consider the impact on a national population. As a referee, I request additional explanation on the following points.
The correlation between IgG and vaccine effectiveness, which is the premise of this study, should be carefully explained in the introduction. For example, I found references below.
Earle, Kristen A., et al. "Evidence for antibody as a protective correlate for COVID-19 vaccines." Vaccine 39.32 (2021): 4423-4428.
Benkeser, David, et al. "Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial." Science translational medicine 15.692 (2023): eade9078.
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript in order to clarify the correlation between IgG index and vaccine effectiveness. Author have also included the reviewer suggested references in the manuscript.
The relationship between the survey for recruiting volunteers and the recruits needs to be explained in detail. Were participants stratified to match the entire society? In the Discussion, the authors discuss the spread of infection in society in general and the effectiveness of vaccines, so they should emphasize that the target population reflects the structure of society as a whole.
If the authors' aim is focused on academic populations, point 2 is not valid. In that case, after adding this to the explanation, the authors should state that the aim of this study is an academic population, and then state in the Discussion that the results of the volunteer group are appropriate for investigating the prevention of the spread of infection in academic populations.
Response: Authors are appreciative and acknowledge the reviewer most relevant comment. This study focused on the assessment of IgG antibodies prevalence against SARS-CoV-2 after vaccination in the academic population, with the aim to address this particular population. Authors have clarified this aim in the manuscript and added the requested information in the Discussion as suggested.
“Nevertheless, in order to ensure the safe reopening of educational institutions, research aiming at SARS-CoV-2 seroprevalence among students, professors, and staff members was crucial. Here we performed a semi-quantitative binding assay to retrospectively measure IgG against SARS-CoV-2 Spike protein to evaluate the magnitude of antibody responses in the academic community of IPL resultant from different vaccination schemes available at the time of sample collection. Analyzed data from IPL volunteers enrolled in this study were used to access the prevention of the spread of infection in academic populations and allowed us to infer the prevalence of SARS-CoV-2 immunity within the IPL academic community.”
Authors have also clarified the aim of the study in the Introduction section.
As the authors state, there has been discussion in previous studies about the correlation between in-person attendance at school and increased transmission of SARS-CoV-2 infection. In addition, many Universities have adopted remote classes to avoid the formation of groups. This is related to 2-3, but the authors should clarify whether the aim of their study is to focus on the effectiveness of vaccines in academic populations or in general society, where vaccination rates were particularly high, and then add a discussion in the Discussion according to the clarified purpose. An example is shown below.
If the aim is to affect society as a whole: Discussion on the extent to which the population size in this study can reflect the overall situation in Portuguese society.
If the aim is an academic population: Discussion on the effectiveness of the vaccine in academic populations by examining the age structure and vaccination rates in general academic populations through literature.
Response: Authors are appreciative and acknowledge the reviewer most relevant comment.
Once more, this study focused on the assessment of IgG antibodies prevalence against SARS-CoV-2 after vaccination in the academic population, with the aim to address this particular population. In order to clarify we have included the text indicated above and included references of studies performed in academic populations, namely:
- DeJonge PM, et al. Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses - fall 2021, Wisconsin. BMC Infect Dis. 2023 Jun 5;23(1):374. doi: 10.1186/s12879-023-08332-7.
- Mitani A, et al. Epidemiological study using IgM and IgG antibody titers against SARS-CoV-2 in The University of Tokyo, Japan (UT-CATS). J Infect Chemother. 2021 Sep;27(9):1342-1349. doi: 10.1016/j.jiac.2021.06.008. Epub 2021 Jun 12. PMID: 34158239; PMCID: PMC8196331.
- Lee CC, et al. A cohort study measuring SARS-CoV-2 seroconversion and serial viral testing in university students. BMC Infect Dis. 2022 Mar 31;22(1):314. doi: 10.1186/s12879-022-07314-5. PMID: 35361140; PMCID: PMC8968700.
Reviewer 2 Report
Comments and Suggestions for Authors1. The numbers for individuals without prior COVID diagnosis after full vaccination or full vaccination+booster does not seem to match the numbers provided in line 19-20 (abstract). Can authors clarify this?
2. Table 1: Why was fully vaccinated+booster population with prior COVID diagnosis not included in the analysis?
3. Section 3.2 and Figure 1: Please indicate that this analysis is for 'full vaccination' population (no booster dose and no prior infection)
4. Figure 2 includes the data shown in Figure 1, so I don't think Figure 1 is necessary. The comparison that the authors are trying to perform in Figure 1 (i.e., IgG index in male vs. female after full vaccination) can be performed on Figure 2 along with comparison for other vaccination schemes. Figure 1 is redundant.
5. Same comment as above for Figure 3 and Figure 4. The data shown in Figure 3 is included in Figure 4, which makes Figure 3 redundant. Authors can perform Dunnett's testing on fully vaccinated group in Figure 4 to make their point.
6. Lines 250-254: These lines are unclear. There seems to something missing. Please review and revise. Please also reference Figure 5 in this section.
7. Lines 327-329: There is no data shown to draw this conclusion about decrease in IgG levels over time.
8. Line 362: "including those of non-vaccinated individuals..." This statement is inconsistent with line 288 which states that all participants in this research received at least one dose of COVID19 vaccine. Can authors clarify if non-vaccinated individuals were included in this study ?
9. It would have been interesting to evaluate individuals without vaccination history but with prior COVID infection in this study to understand how IgG index in unvaccinated population (but exposed to COVID) compared to vaccinated individuals.
Other minor comments:
1. Line 89: to 'retrospectively' measure
2. Line 143: Typo t-test
3. Line 202: Typo - significantly
4. Line 203: Please change to 'wherein' instead of 'whereas'
5. Line 300: SARS-CoV-2 instead of SARS-CoV
Author Response
Dear reviewer,
Authors are appreciative and acknowledge the reviewer criticism and hereby reply in concordance with the indicated comments in order to clarify and improve the manuscript.
Comments and Suggestions for Authors:
- The numbers for individuals without prior COVID diagnosis after full vaccination or full vaccination+booster does not seem to match the numbers provided in line 19-20 (abstract). Can authors clarify this?
Response: Authors acknowledge the reviewer comment. In order to clarify, we have included in the abstract information regarding individuals that received a full vaccination and a booster dose of the same vaccine (81) and mixed vaccines (33) which together is 114. …” Individuals without a prior COVID-19 diagnosis were divided into two groups: 350 who received a full vaccination, and 114 who received a full vaccination and a booster dose of the same vaccine (81) and mixed vaccines (33)…”
- Table 1: Why was fully vaccinated+booster population with prior COVID diagnosis not included in the analysis?
Response: Authors acknowledge the reviewer comment. In order to clarify, we did not have any volunteer with those parameters included in the study. Data analysis was performed in volunteers enrolled in the study and in demographic characteristics and vaccination scheme analysis no fully vaccinated+booster with prior COVID diagnosis individual was identified.
- Section 3.2 and Figure 1: Please indicate that this analysis is for 'full vaccination' population (no booster dose and no prior infection)
Response: Authors acknowledge the reviewer criticism and have revised the manuscript in order to clarify that Figure 1 data refers to 'full vaccination'.
- Figure 2 includes the data shown in Figure 1, so I don't think Figure 1 is necessary. The comparison that the authors are trying to perform in Figure 1 (i.e., IgG index in male vs. female after full vaccination) can be performed on Figure 2 along with comparison for other vaccination schemes. Figure 1 is redundant.
Response: Authors are appreciative and acknowledge the reviewer most relevant comment. Nevertheless, although IgG antibodies index differences regarding sex can also be seen in Figure 2, authors want to emphasize the overall divergence in male and female for fully vaccinated individuals and with figure 1 we believe that it is clearer for the reader.
- Same comment as above for Figure 3 and Figure 4. The data shown in Figure 3 is included in Figure 4, which makes Figure 3 redundant. Authors can perform Dunnett's testing on fully vaccinated group in Figure 4 to make their point.
Response: Authors are appreciative and acknowledge the reviewer most relevant comment. Nevertheless, once more, authors wanted to facilitate the readers data analysis and emphasize the SARS-CoV-2 IgG antibodies index by age group in Figure 3.
- Lines 250-254: These lines are unclear. There seems to something missing. Please review and revise. Please also reference Figure 5 in this section.
Response: Authors acknowledge the reviewer's criticism and have revised the manuscript.
- Lines 327-329: There is no data shown to draw this conclusion about decrease in IgG levels over time.
Response: Authors acknowledge the reviewer's criticism and have revised the manuscript.
- Line 362: "including those of non-vaccinated individuals..." This statement is inconsistent with line 288 which states that all participants in this research received at least one dose of COVID19 vaccine. Can authors clarify if non-vaccinated individuals were included in this study ?
Response: Authors acknowledge the reviewer's criticism and have revised the manuscript. In fact, in this study all participants in this research received at least one dose of COVID19 vaccine.
- It would have been interesting to evaluate individuals without vaccination history but with prior COVID infection in this study to understand how IgG index in unvaccinated population (but exposed to COVID) compared to vaccinated individuals.
Response: Authors acknowledge the reviewer's most pertinent comment. It would be interesting to access IgG index levels in unvaccinated individuals, however this study was designed as a retrospective post-vaccination study focused in SARS-CoV-2 immunization index in the academic community. Thus, our population was vaccinated individuals. Nevertheless, we had extremely high vaccination index in our academic community, and therefore unvaccinated individuals were extremely rare.
Other minor comments:
- Line 89: to 'retrospectively' measure
- Line 143: Typo t-test
- Line 202: Typo - significantly
- Line 203: Please change to 'wherein' instead of 'whereas'
- Line 300: SARS-CoV-2 instead of SARS-CoV
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript regarding all the indicated minor comments.
Reviewer 3 Report
Comments and Suggestions for AuthorsContained in the attached document.
Comments for author File: 
Comments.pdf
A native English speaker is advised to edit the grammar.
Author Response
Dear reviewer,
Authors are appreciative and acknowledge the reviewer criticism and hereby reply in concordance with the indicated comments in order to clarify and improve the manuscript.
The article entitled “SARS-CoV-2 immunization index in the academic community: A retrospective post-vaccination study” is well-written. However, the authors are kindly advised to attend to a few minor reviews below.
1.Line 45-46, “In two years of pandemic, Portugal had roughly 4.89 million confirmed COVID-19 cases and 23.490 deaths” should be corrected the pandemic and the figure 23.490 deaths verified.
Response: Authors acknowledge the reviewer comment. In order to clarify, data is referred to two years of the pandemic in Portugal, which were at time of the study.
- Lines 47-47, “Despite only 14% of individuals infected with SARS-CoV-2 developing severe disease, the high transmission rates leading to a high number of patients seeking hospital care, represented a massive burden for national health systems, many of which have nearly collapsed in certain countries that have been severely affected by the pandemic” is ambiguous and should be rephrased in two more concise sentences.
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript.
- Kindly rephrase this ambiguous sentence “COVID-19 (coronavirus infectious disease 2019) virus was declared as an outbreak of public health emergency of international concern (PHEIC) by the World Health Organization (WHO) on 30 January 2020, which quickly spread worldwide, causing a pandemic declared at 11 March, that reached approximately 545 million confirmed cases and 6.33 million deaths (lines 40-43)
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript.
- The authors are advised to address the repetitive use of “In this study” (lines 123, 154, 247, 351).
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript.
- Generally, there are too many ambiguities in the grammar, therefore, a native English speaker should be consulted to assist.
Response: Authors acknowledge the reviewer's suggestion and have revised the manuscript.
