A Paradigm Shift: The Reclassification of SARS-CoV-2 and Longitudinal Immune Responses in Japanese Healthcare Workers

Round 1

Reviewer 1 Report

This study is important because it makes it clear that the combination of humoral immunity (vaccines and infections) with cellular immunity (essentially produced by infection) is a widespread condition and alone is sufficient as an immune barrier, even despite the possible onsets of new viral variants.

No suggestions. 

Author Response

Comments 1: This study is important because it makes it clear that the combination of humoral immunity (vaccines and infections) with cellular immunity (essentially produced by infection) is a widespread condition and alone is sufficient as an immune barrier, even despite the possible onsets of new viral variants.

Response 1: Thank you for your favorable comments.  However, we also refer to the comment of another reviewer and add that hybrid immunity against SARS-CoV-2 by vaccine and natural infection is better than that caused solely by vaccination, and contributes to form the herd immunity of HCWs (Page 4, Line 147-156).

 

Reviewer 2 Report

This is a longitudinal study of COVID-19 vaccine-induced immune responses after the pandemic. The study is sound, but the cohort size is too small. However, it cannot increase the number of cases at this point. Anyway, this study provides a clear idea for public health policy although it is bit too late.

No clear information about the ethic issues. No proper control groups （such as people without vaccination and people with no further vaccination)

The data presentation need to improve, such as giving some plots of  typical cases against the time. Display anti-spike and other antibodies in different panel for easy reading etc.

Author Response

Major Comments 1: This is a longitudinal study of COVID-19 vaccine-induced immune responses after the pandemic. The study is sound, but the cohort size is too small. However, it cannot increase the number of cases at this point. Anyway, this study provides a clear idea for public health policy although it is bit too late.   Response 1: Thank you for your favorable comments. We have improved the paper by responding to the following points you made and we hope to ask you to re-evaluate it.     Detail Comments 2: No clear information about the ethical issues. No proper control groups (such as people without vaccination and people with no further vaccination)   Response 2: Please refer to "Institutional Review Board Statement" and "Informed Consent Statement" on Page 5 for ethical information. In the 2022 study of 1600 subjects, there were only two unvaccinated cases, but their follow-up was not possible. Instead, a comparison was made with those who were not naturally infected with SARS-CoV-2 and formed immunity only with the vaccine. The results showed that the population immunized by hybrid immunity acquired three times stronger immune characteristics than those immunized by vaccine alone (Page5, Line 147-156).     Detail Comments 3: The data presentation needs to improve, such as giving some plots of typical cases against the time. Display anti-spike and other antibodies in different panel for easy reading etc.   Response 3: In accordance with your helpful comments, we have also included data on the evolution of Nucleocapsid IgG values (Supplementary Material 3). Then, we've also added the reasons for the underestimation compared to the actual number of diagnosed COVID-19 cases (Page 3, Line 130-134).

Round 2

Reviewer 2 Report

the authors have answered most of my comments and changed the figures.

The controls are difficult to include due to the real situation

The reference number is too small. There are too many publication and some of them are relevant and can be added