Review Reports - COVID-19 Double Annual Epidemic Peaks in Summer and in Winter from 2022, Irrespective of the Rate of Mask Wearing and Vaccination

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

For the authors

I Attach the word file where the critical issues of this work are described, point by point.

Regards

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Dear authors

The English is understandable but contains numerous small errors and phrases that sound unnatural for a scientific paper.

Exaples: "Meanwhile, mask wearing has been associated with a bioaccumulation..." >better: "Meanwhile, prolonged mask use has been suggested to be associated with bioaccumulation..."

"The vaccination in 2021 coincided with the large increase..." >better: "The vaccination rollout in 2021 coincided with a large increase..."

There is also improper use of tenses and prepositions throughout the text.

A full language revision by a native English-speaking editor with experience in scientific writing is strongly recommended.

Author Response

1) Analysis of scientific content

Originality and Framework

The topic is certainly very timely and of public interest: it examines the relationship between the COVID-19 epidemic trend in Japan, vaccination coverage, mask use, and a possible side effect (bioaccumulation of microplastics).

The idea of correlating epidemiological trends with environmental and behavioral factors (vaccination and mask use) is conceptually interesting and original. However, the treatment appears methodologically weak and not scientifically solid enough for publication in a peer-reviewed journal of good standing.

[Response from authors]

Thank you for your comment.

We revised our manuscript thoroughly with regard to the interpretation of study results and limitations of our study.

We also added—in Discussion,

Our recent study, which compared previous several influenza epidemics and COVID-19 epidemics, showed that the growth of these respiratory epidemics are sim-ilar and that the rate of spread seemed to largely reflect climate circumstances;—in winter, the incidence rate exponentially increased irrespective of mask wearing and in summer the rate of increase of the incidence rate slowed down.[11]

Main Scientific Issues

Lack of causal analysis: The text describes correlations (e.g., the increase in cases after the start of vaccination) but does not control for confounding variables such as the emergence of new variants, changes in public health policies, population mobility, testing intensity, etc.

Potentially misleading interpretations: Statements such as “the incidence increased after vaccination, therefore the efficacy is doubtful” are not scientifically justified without robust statistical analysis.

[Response from authors]

We have thoroughly revised throughout to give a more nuanced interpretation.

Microplastics and masks: The link between mask use and an increase in microplastics in the brain or other tissues is presented without verifiable references. Citing a single study (“[3]”) is insufficient — the author must specify the journal, authors, and methodology.

The claim that “PVC is used in the nasal part of masks and can reach the brain” is highly speculative and requires direct experimental evidence.

[Response from authors]

We revised as;

L39-Introduction

Meanwhile, mask wearing has been associated with a bioaccumulation of microplastics in the human body; microplastics of disposable medical face masks, including poly-propylene (PP), polyethylene (PE), polycarbonate, polyester/polyethylene terephthalate, polyamide/Nylon, polyvinylchloride, and ethylene-propylene copolymer were detect-ed.[4, 5] Another study found increased levels of PE, PP, and polyvinyl chloride (PVC) in the brain, kidney, and liver in decedent tissue samples. [6] The amount of microplastics in such tested tissue samples more rapidly increased during the COVID-19 pandemic years, with a 50% significant increase in 2024 samples as compared with 2016 samples of brain tissues.[6]

L166-Discussion

Logically, PVC exposure would increase with mask wearing [3]. Another study has presented that fourier transform infrared spectroscopy and electron microscopy con-firm the presence of microplastics and nanoplastics in human organs in US, such as liver and brain.[5] Between 2016 and 2024, PVC concentration in the brain tissue sample of decedents increased approximately 5 times.[5]

Conclusions

The conclusions go beyond the data presented. Statements such as “vaccination did not reduce case numbers” or “mask efficacy is limited” require controlled studies, not descriptive analyses.

[Response from authors]

We have written a much more nuanced discussion of the observations.

Similarly, the claim that “climate change better explains the epidemic trend” is interesting but would require statistical modeling (e.g., multivariate regression), which is not shown.

In summary: the work is original in concept but scientifically weak in methodology and in its inferences.

[Response from authors]

We have added more explanation of our recent research regarding climate factors in Discussion.

“Our recent study, which compared previous several influenza epidemics and COVID-19 epidemics, showed that the growth of these respiratory epidemics are sim-ilar and that the rate of spread seemed to largely reflect climate circumstances;—in winter, the incidence rate exponentially increased irrespective of mask wearing and in summer the rate of increase of the incidence rate slowed down.[11]”

2) Structure and Organization

The paper formally follows a correct structure (Introduction, Methods, Results, Discussion).

However, the Methods section is far too brief and lacks essential information: time period analyzed, data sources, type of statistical analysis, software used, and criteria for defining “epidemic peak.”

[Response from authors]

We revised the Methods thoroughly.

Figures are mentioned (Fig. 1A, Fig. 3) but not described or included, making interpretation difficult.

[Response from authors]

We revised the visibility of Figures and added the explanation of the Figure in each Figure legend.

The Discussion is long and often repetitive, and includes many hypotheses that are not supported by data.

[Response from authors]

We revised the Discussion thoroughly.

3) Publishability and Recommendations

In its current form:

The paper is not ready for publication in a peer-reviewed scientific journal.

It might be acceptable only as a working paper, preprint, or opinion piece, but not as an original research article.

To make it publishable:

Strengthen the methods: clearly describe data sources, introduce robust statistical analyses, and control for confounding variables.

Reduce speculative statements: clearly distinguish between correlation and causation.

[Response from authors]

Thank you for your comment.

We revised our manuscript thoroughly with regard to the interpretation of study results and limitation of our study.

Verify bibliographic references, especially those regarding microplastics (they must be scientific publications, not opinion pieces).

[Response from authors]

We revised our manuscript as above accordingly.

Thoroughly revise the English to improve clarity, fluency, and technical precision.

[Response from authors]

We revised our manuscript accordingly.

Restructure the Discussion to focus on verifiable results rather than personal interpretations.

[Response from authors]

We revised our manuscript as above accordingly.

Reviewer 2 Report

Comments and Suggestions for Authors

This opinion letter discusses COVID-19 epidemic patterns in Japan from 2021-2024, attempting to correlate incidence rates with vaccination coverage and mask stock. The authors conclude that vaccination coverage and mask use have limited impact on disease transmission. However, the methods used to analyze and interpret data are not statistically and logically sound, which fundamentally undermines the conclusion drawn, although I personally agree that some suggestions mentioned at the end of this manuscript are valuable for further discussion.

Comments:

The results are based on retrospective and observational studies. Comparing observational data to evaluate vaccine is methodologically less powerful for establishing causation. The authors have used some statistics like CI and case increase ratios. However, rigorous statistical and correlation testing or modelling have not been performed, which is especially critical in this observational study involving both continuous and discrete data types.
For such retrospective and observational studies, the assumptions made and chosen could largely impact the conclusions drawn. For example, the emergence of the Omicron variant clearly made two different phases of virus fitness and transmissibility. If the authors compared the data pre-Omicron (2021-2022) and post-Omicron (2023-2024) separately, then different trends and implications could be discovered.
There are many confounding variables that are not mentioned, statistically compared, or discussed, including but not limited to: variant fitness and evolution, changes in testing and surveillance, behavioral and social measures. Many of these factors are likely correlated with the incident number data used in this manuscript. Without proper control, it could not be determined which is the principal component driving observed correlations.
The authors discussed vaccine efficacy as a potential confounding factor. Even if this manuscript provided a statistically sound correlation between vaccine administration and incident cases, the effects of vaccination on severity and hospitalization are equally or more important outcomes that are not addressed. I agree with the last sentence the authors stated about hospital capacity. As an opinion, things should be discussed more deeply could be whether vaccine administration and mask usage are initially more convenient way to deal with beds and hospitalization limitations.
As mentioned in Point 3, if not discussed, the authors should mention the factors such as changes in testing and surveillance, behavioral and social measures, and the definition of mask stock and vaccines used. The author should also address the limitation on the correlation between mask stock and incident cases. The mask stock data could only reflect that during a certain period, the total masks fabricated, imported, stocked, sold at a national or societal scale. Does that really reflect the mask usage? I personally stocked 300 masks at home during 2020-2021, but only stock 50 afterwards. However, I kept the same 1-per-day usage throughout. I don’t think this is an uncommon situation. National inventory levels do not reliably reflect individual usage patterns. Assessing mask use against incident cases is also tricky, as one may not wear masks at home with other members. Therefore, such an observational study analyzing mask stock to interpret mask use to infer protection from viral infection is not methodologically solid.

Author Response

[Response from authors]

Thank you for your comment.

We revised our manuscript thoroughly with regard to the interpretation of study results and limitations of our study.

Comments:

The results are based on retrospective and observational studies. Comparing observational data to evaluate vaccine is methodologically less powerful for establishing causation. The authors have used some statistics like CI and case increase ratios. However, rigorous statistical and correlation testing or modelling have not been performed, which is especially critical in this observational study involving both continuous and discrete data types.

[Response from authors]

Thank you for your comment.

We revised our manuscript thoroughly with regard to the interpretation of study results and limitation of our study.

For such retrospective and observational studies, the assumptions made and chosen could largely impact the conclusions drawn. For example, the emergence of the Omicron variant clearly made two different phases of virus fitness and transmissibility. If the authors compared the data pre-Omicron (2021-2022) and post-Omicron (2023-2024) separately, then different trends and implications could be discovered.

[Response from authors]

Thank you for your comment.

The result was revised with the clarity of emergence of Omicron variant, as follows.

The weekly case increase ratio in the 5 weeks before the epidemic peak week increased 195 times in the 6th wave in the beginning of 2022 when the omicron variant became predominant. The average of the weekly case increase ratio before the vaccination (3rd and 4th waves) was 1.85 (95% confidence interval [CI]: 1.53—2.17]), and the average of 5th and 7th wave covering the period during and after the implementation of intensive vaccination was 5.94 (95%CI:-7.05—18.94); this excludes the largest increase ratio in the 6th (when the Omicron variant appeared). The average of the case increase ratio for the subsequent five epidemic waves after the massive vaccination was 1.86 (95%CI:1.04—2.68) (Fig. 1B)

There are many confounding variables that are not mentioned, statistically compared, or discussed, including but not limited to: variant fitness and evolution, changes in testing and surveillance, behavioral and social measures. Many of these factors are likely correlated with the incident number data used in this manuscript. Without proper control, it could not be determined which is the principal component driving observed correlations.

[Response from authors]

We revised our manuscript thoroughly with regard to the interpretation of study results and limitations of our study.

The authors discussed vaccine efficacy as a potential confounding factor. Even if this manuscript provided a statistically sound correlation between vaccine administration and incident cases, the effects of vaccination on severity and hospitalization are equally or more important outcomes that are not addressed. I agree with the last sentence the authors stated about hospital capacity. As an opinion, things should be discussed more deeply could be whether vaccine administration and mask usage are initially more convenient way to deal with beds and hospitalization limitations.

[Response from authors]

We revised our manuscript thoroughly with regard to the interpretation of study results and limitation of our study.

As mentioned in Point 3, if not discussed, the authors should mention the factors such as changes in testing and surveillance, behavioral and social measures, and the definition of mask stock and vaccines used. The author should also address the limitation on the correlation between mask stock and incident cases. The mask stock data could only reflect that during a certain period, the total masks fabricated, imported, stocked, sold at a national or societal scale. Does that really reflect the mask usage? I personally stocked 300 masks at home during 2020-2021, but only stock 50 afterwards. However, I kept the same 1-per-day usage throughout. I don’t think this is an uncommon situation. National inventory levels do not reliably reflect individual usage patterns. Assessing mask use against incident cases is also tricky, as one may not wear masks at home with other members. Therefore, such an observational study analyzing mask stock to interpret mask use to infer protection from viral infection is not methodologically solid.

[Response from authors]

We revised our manuscript thoroughly with regard to the interpretation of study results and limitations of our study.

Discussion

Our analysis is clearly limited by correlating patterns of vaccination coverage, mask use and incidence rates over time without any information on confounding factors such as social activity, testing rates and actual mask use. However, the in vitro demonstration that Omicron is an immune escape variant does concur with our findings that suggest ineffective vaccine efficacy.[3]

Reviewer 3 Report

Comments and Suggestions for Authors

Abstract

Lines 14–21: The abstract overstates conclusions (e.g., “limited impact of vaccination or masks”) without acknowledging confounding factors such as variant shifts and seasonality. Rephrase to be more cautious and evidence-based.

Lines 22–29: The sentence suggesting vaccination “coincided with” epidemic growth implies causation without analysis. This needs clarification and toned-down wording.

Introduction

Lines 37–44: The discussion of microplastics and mask risk is disproportionate to the main epidemiological question and relies on a single recent study. Reduce emphasis or expand supportive references.

Lines 45–46: The research question is stated but does not clearly describe the hypothesis. Clarify the objective and expected relationship between variables.

Methods

Lines 48–53: Data sources are named but data extraction and processing steps are not described clearly enough to permit replication. Include date ranges, inclusion criteria, and definition of “incidence rate.”

Lines 49–50: The method of calculating the “weekly case increase ratio” needs a clear formula and reasoning. Currently ambiguous.

Results

Lines 52–63: Statements suggest causality (e.g., vaccination leading to increased cases). These should be revised as observational correlations unless supported by modeling or controls.

Lines 75–88: The two-wave seasonal pattern is described, but alternative explanations (e.g., immunity dynamics, Omicron characteristics) are not discussed. Avoid implying the observed pattern is driven by vaccination.

Figure 1 & 2: Figures lack confidence intervals or adjustment for population size; visual interpretation may mislead. Clarify scale and normalization.

Discussion

Lines 109–124: The manuscript concludes vaccination had limited effect, but this is not supported by controlled analysis. This section needs substantial softening or statistical justification.

Lines 143–148: The claim linking mask use to increased microplastics in humans is speculative relative to the evidence presented. Clarify uncertainty and avoid policy recommendations based on a single emerging study.

Comments on the Quality of English Language

The manuscript would benefit from careful English editing to improve clarity and readability. Several sentences are complex or ambiguous, and some phrasing may lead to misinterpretation of the scientific meaning. A thorough grammatical and stylistic revision is recommended to enhance precision and flow.

Author Response

Abstract

[Response from authors]

Thank you for your comment.

We revised as,

L25-Abstract

The rapid growth in COVID-19 infections at the time of the vaccine implementation suggests that further analysis is needed regarding vaccine efficacy.

Lines 22–29: The sentence suggesting vaccination “coincided with” epidemic growth implies causation without analysis. This needs clarification and toned-down wording.

[Response from authors]

We have revised this to not give such an impression.

Introduction

[Response from authors]

We revised as,

L39-introduction

Meanwhile, mask wearing has been associated with a bioaccumulation of microplas-tics in the human body; microplastics of disposable medical face masks, including polypropylene (PP), polyethylene (PE), polycarbonate, polyester/polyethylene tereph-thalate, polyamide/Nylon, polyvinylchloride, and ethylene-propylene copolymer were detected.[4, 5] Another study found increased levels of PE, PP, and polyvinyl chloride (PVC) in the brain, kidney, and liver in decedent tissue samples. [6] The amount of microplastics in such tested tissue samples more rapidly increased during the COVID-19 pandemic years, with a 50% significant increase in 2024 samples as compared with 2016 samples of brain tissues.[6] This risk puts more emphasis on establishing the benefits of mask wearing to prevent disease spread.

L174-Discussion

With regard to mask use, there is concern that their microplastics have detrimental ef-fects on human health. For instance, PVC, a known carcinogen, is used in the nose-fitting of masks and also other daily items, such as plastic bags. Inhaled PVC can go to the lung and also to the brain through olfactory cells together with other micro-plastics. Logically, PVC exposure would increase with mask wearing. [4] Another study using infrared spectroscopy and electron microscopy confirmed the presence of microplastics and nanoplastics in human organs, such as the liver and brain.[6] Be-tween 2016 and 2024, PVC concentration in the brain tissue sample of decedents in-creased approximately 5 times.[6] This thus underlines the importance of more de-tailed studies on the efficacy of the different types of masks against respiratory infec-tions prior to the next pandemic.

Lines 45–46: The research question is stated but does not clearly describe the hypothesis. Clarify the objective and expected relationship between variables.

[Response from authors]

We have revised as,

Introduction

In light of the uncertain efficacy of the vaccine against the Omicron variant and the unknown impact of mask wearing, we compared the epidemic pattern with vaccination coverage, and mask use.

Methods

[Response from authors]

We revised the Methods thoroughly.

Lines 49–50: The method of calculating the “weekly case increase ratio” needs a clear formula and reasoning. Currently ambiguous.

[Response from authors]

We revised the Methods thoroughly.

Results

Lines 52–63: Statements suggest causality (e.g., vaccination leading to increased cases). These should be revised as observational correlations unless supported by modeling or controls.

[Response from authors]

We revised our manuscript thoroughly with regard to the interpretation of study results and limitation of our study.

[Response from authors]

We have attempted to tone this down throughout.

Figure 1 & 2: Figures lack confidence intervals or adjustment for population size; visual interpretation may mislead. Clarify scale and normalization.

[Response from authors]

We have added our explanation in the figure legends as below.

“Decimal numbers are the crude incidence rates (%) per population (0.12 billion).for each wave. B. Weekly case increase ratio for 5 weeks before the peak week. Light green bars show vaccine in-tensive period and 95% confidence intervals are shown as vertical black bars”

Discussion

Lines 109–124: The manuscript concludes vaccination had limited effect, but this is not supported by controlled analysis. This section needs substantial softening or statistical justification.

[Response from authors]

We have revised our manuscript thoroughly with regard to the interpretation of study results and limitations of our study.

[Response from authors]

We have revised as above.

Comments on the Quality of English Language

[Response from authors]

We have revised our manuscript thoroughly for improved interpretation and readability.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors

The your manuscript can be published after minor revision in terms of clarity, precision, structure and especially editing service (english needs to be improved).

Best regards

Comments on the Quality of English Language

Dear authors

The English is understandable but contains numerous small errors and phrases that sound unnatural for a scientific paper.

Exaples: "Meanwhile, mask wearing has been associated with a bioaccumulation..." >better: "Meanwhile, prolonged mask use has been suggested to be associated with bioaccumulation..."

"The vaccination in 2021 coincided with the large increase..." >better: "The vaccination rollout in 2021 coincided with a large increase..."

There is also improper use of tenses and prepositions throughout the text.

A full language revision by a native English-speaking editor with experience in scientific writing is strongly recommended.

Author Response

The English is understandable but contains numerous small errors and phrases that sound unnatural for a scientific paper.

Exaples: "Meanwhile, mask wearing has been associated with a bioaccumulation..." >better: "Meanwhile, prolonged mask use has been suggested to be associated with bioaccumulation..."

"The vaccination in 2021 coincided with the large increase..." >better: "The vaccination rollout in 2021 coincided with a large increase..."

There is also improper use of tenses and prepositions throughout the text.

A full language revision by a native English-speaking editor with experience in scientific writing is strongly recommended.

[Response from authors]

Thank you for your comment.

English has been edited by a native English scientist.

Reviewer 2 Report

Comments and Suggestions for Authors

This revised manuscript has addressed some of the limitations in the analysis. However, while this opinion discusses two interventions for viral infections, vaccination and mask use, and compares their potential downsides, the logic and correlations presented are still not sufficiently solid.

As mentioned in my previous comments, “As an opinion, things should be discussed more deeply could be whether vaccine administration and mask usage are initially more convenient way to deal with beds and hospitalization limitations.” Vaccination should not be solely considered for prevention. If Fig.1 or 2 could also include the severe cases, hospitalizations, and death numbers, then the discussion of vaccination coverage during COVID-19 would be more vigorous.

Similar to the mask use discussion, the cited reference studies discussed two major findings about micro- and nano-plastics (MNPs): bioaccumulation of microplastics detected in human brain tissue and increased from 2016 to 2024 samples; and worn and wet masks could release MNPs according to mask types and materials. This should not infer that mask use during COVID-19 is responsible for this bioaccumulation, but rather should highlight the importance of adequate mask stocks so that people do not have to wear the used/worn/wet masks.

There are also many formatting issues and typos in this revised manuscript. Some of the references are mismatched and misaligned in the main text due to the editing and/or insertion in the main text.

Author Response

[Response from authors]

Thank you.

We revised the title and manuscripts thoroughly.

Abstract:

From 2022, two annual epidemic peaks occurred with seasonal changes. Whilst the winter peak follows the expected seasonal trend in respiratory infections, the summer peak may reflect a combination of short-term herd immunity and behavioral patterns. Nevertheless, these epidemic peaks continued irrespective of vaccine coverage and mask use. Further analysis into the duration of protective efficacy of the vaccines and mask use is required.

Discussion:

From 2022, there were two epidemic peaks each year, in summer and winter, irrespective of the extent of vaccine coverage or mask use. The weekly case increase ratio in the number of cases started to increase in the winter following the implementation of the mass vaccination program.

This sudden increase in the incidence rate despite vaccination with the arrival of the Omicron variant concurs with the evidence suggesting that it is an immune escape variant. [3]

That there were also summer peaks requires alternative explanations. Such peaks may reflect the acquisition of only short-term immunity, whether induced by the vaccine or naturally acquired and/or changes in behavior. That these summer peaks occurred irrespective of vaccine coverage calls into question its efficacy.

-------------------------------

[Response from authors]

We revised as,

Introduction:

Meanwhile, mask wearing has been suggested to be associated with a bioaccumula-tion of microplastics in the human body; microplastics of disposable medical face masks, including polypropylene (PP), polyethylene (PE), polycarbonate, polyes-ter/polyethylene terephthalate, polyamide/Nylon, polyvinylchloride, and eth-ylene-propylene copolymer have been detected in organs.[5, 6] Another study found increased levels of PE, PP, and polyvinyl chloride (PVC) in the brain, kidney, and liver in decedent tissue samples. [7] The amount of microplastics in such tested tissue sam-ples increased more rapidly during the COVID-19 pandemic years, with a 50% signif-icant increase in 2024 samples as compared with 2016 samples of brain tissues.[7] This risk puts more emphasis on establishing the benefits of mask wearing to prevent dis-ease spread. In light of the uncertain efficacy of the vaccine against the Omicron vari-ant and the unknown impact of mask wearing, we compared the epidemic pattern with vaccination coverage, and mask use.

Discussion:

With regard to mask use, it is possible that actual mask use in the hot summer months may have decreased and/or the masks themselves became less efficient. However, considering the concern that microplastics in masks have detrimental effects on human health, more detailed studies on the efficacy and durability of the different types of masks as well as their acceptability need to be carried out. This should then be weighed up against other non-pharmaceutical interventions (e.g. hand-washing, self-imposed isolation when ill) as measures for reducing transmission of respiratory infections prior to the next pandemic.[19] This information would enable a rationale allocation of funds to personal protective equipment as opposed to collective measures, including resources for improving response capacity to control outbreaks.

-------------------------------------

There are also many formatting issues and typos in this revised manuscript. Some of the references are mismatched and misaligned in the main text due to the editing and/or insertion in the main text.

[Response from authors]

We have examined the references.

English has been edited by a native English scientist.

References are also numbered correctly.

Reviewer 3 Report

Comments and Suggestions for Authors

My comments were addressed.

This manuscript can be considered for publication.

Author Response

Thank you.

We appreciate your review.