Links between COVID-19 and Alzheimer’s Disease—What Do We Already Know?

Round 1

Reviewer 1 Report

The manuscript by Rudnicka-Drożak et al. is an interesting review reporting the relationship between Alzheimer's disease and COVID-19. The paper is well written and constitutes a relevant contribution for all the scientists working in these fields. I believe that the paper will have a major impact if the authors will include additional figures and/or tables highlighting the most outstanding findings. 

Author Response

Dear Sir or Madam, thank You very much for the review of the manuscript entitled: “Links between COVID-19 and Alzheimer’s disease – what we already know?”.

In response to Your comments, we would like to thank You for appreciating our manuscript.

Manuscript changes are highlighted in yellow.

Comment

The manuscript by Rudnicka-Drożak et al. is an interesting review reporting the relationship between Alzheimer's disease and COVID-19. The paper is well written and constitutes a relevant contribution for all the scientists working in these fields. I believe that the paper will have a major impact if the authors will include additional figures and/or tables highlighting the most outstanding findings.

Revision and my comment

Thank You for the positive feedback of our manuscript.

 

We do honestly hope that it will satisfy You and improve the quality of our work. Once again we are very grateful for Your review and remain open if You have any other remarks or suggestions that will make our work merit publication in “International Journal of Environmental Research and Public Health”.

Sincerely,

Paulina Drożak on behalf of the authors

 

Reviewer 2 Report

Dear Dr.,

Title: Links between COVID-19 and Alzheimer’s disease – what we 2 already know?

Manuscript ID: ijerph-2158004

Overall comments: Authors described in this review manuscript: the connection between COVID-19 viral infection and Alzheimer’s disease. The ACE2 overexpression mediated entry of SARS-CoV-2 virus in AD brains via reduction of brain-derived neurotrophic factor (BDNF). Even, the ApoE-ε4 allele also raises the risk of AD, with the facilitation of SARS-24 CoV-2 entry into cells. Overall this manuscript is well written. However, some of the contents need to improve for the better quality of this manuscript.

 

Specific comments:

1. The abstract section is well written.

2. In the introduction section, the abbreviation ‘not otherwise specified (NOS)’ can be removed or can place another way because pharmacologically it has a different meaning.

3. In section 2. COVID-19 and dementia: a bidirectional risk; the abbreviation is explained clearly i.e., ….. (OR=3.07 95% CI 1.71 to 5.50) for severe SARS-CoV-2 infection, stronger than COPD, ………..

4. Section 4 has the smallest paragraph with limited information. Hence, it needs to rewrite with more clear and relevant information.

5. Figure 1: It is not clear and needs to rewrite with clear statements & relevant references.

6. Section ‘8.1. Future direction’ can be placed as the main headings.

 

*****

Author Response

Dear Sir or Madam, thank You very much for the review of the manuscript entitled: “Links between COVID-19 and Alzheimer’s disease – what we already know?”.

In response to Your comments, we would like to thank You for appreciating our manuscript.

Manuscript changes are highlighted in yellow.

 

Comment 1

The abstract section is well written.

Revision and my comment

Thank You for the positive feedback.

 

Comment 2

In the introduction section, the abbreviation ‘not otherwise specified (NOS)’ can be removed or can place another way because pharmacologically it has a different meaning.

Revision and my comment

This abbreviation (NOS) is now removed from the text.

 

Comment 3

In section 2. COVID-19 and dementia: a bidirectional risk; the abbreviation is explained clearly i.e., ….. (OR=3.07 95% CI 1.71 to 5.50) for severe SARS-CoV-2 infection, stronger than COPD, ………..

Revision and my comment

Explanations of abbreviations OR, CI, COPD were added in the text (lines 99-101), as well as in the Abbreviations section (lines 440, 417, 419, respectively).

 

Comment 4

Section 4 has the smallest paragraph with limited information. Hence, it needs to rewrite with more clear and relevant information.

Revision and my comment

We don’t agree with this comment, since section 4. is actually the longest one and is very rich in information.

 

Comment 5

Figure 1: It is not clear and needs to rewrite with clear statements & relevant references.

Revision and my comment

An explanation of the arrows and lines was added in the description under the Figure 1. Also, a brief description of the role of ACE2 receptor was added (lines 204-210). A more detailed description of processes illustrated in the Figure 1. is provided in the whole Paragraph 4. Angiotensin-converting enzyme 2 (ACE2) receptor, thus we avoided giving too long descriptions under Figure 1.

 

Comment 6

Section ‘8.1. Future direction’ can be placed as the main headings.

Revision and my comment

We placed ‘Future directions’ as a different section (line 384).

 

We do honestly hope that it will satisfy You and improve the quality of our work. Once again we are very grateful for Your review and remain open if You have any other remarks or suggestions that will make our work merit publication in “International Journal of Environmental Research and Public Health”.

Sincerely,

Paulina Drożak on behalf of the authors

 

Reviewer 3 Report

The revision entitled "Links Beteween Covid-19 and Alzheimer's Disease - What We Already Know?", Of Drożak et al., try to order the most recent articles that highlight the possible links between Alzheimer's disease (AD) and the recent emergence of the Sars-Cov-2 virus that led to the new disease known as Covid-19. 

The article tries to cover, in light of the latest research, the connections between Covid-19 disease and AD, including the clinical presentation of the Sars-Cov-2 infection in patients with AD; potential associated molecular mechanisms (Like: ACE2 receptor, ApoE, Neuroinflammation e oxidative stress) that can be exploited by the Covid-19 virus; the neuropsychiatric symptoms and the cognitive decline of individuals with the effects of the social measures taken during these two years of pandemic on mental health. The evidence brought by the article suggest a close relationship between Alzheimer's and Covid-19 disease, on which it is necessary to develop and implement preventive strategies, even in the long term, adequate if we would reduce the risk of developing the AD and other types of dementia in people infected with Sars-Cov-2. 

I am very happy for having had the opportunity to read this preview study that I find easy and quickly reading without failing to suggest very important conclusions.

After reading this work I have no specific requests for the authors regarding the content but I have anyway two minor requests for the authors only regarding the form. 

1. In general, I think it would be preferable not to use the form "One study described ..." (page 7, line 316) or "Another study also reported ..." (page 7, line 317) to indicate certain works or results that you want to introduce into the discussion, above all, as in the specific case as an example, if the study is not cited (missing citation?).

I therefore suggest that these sentences be replaced where necessary in the article with the name of the author, or group, followed by the appropriate citation. 

1.1 Citations missing, or not directly identifiable, appear to be on page 4, lines 162 and 173, for point 4.1. “Overlaps between ACE2 and COVID-19” and page 7, line 317 for point 7.1. "Neuropsychiatric symptoms and cognitive decline". I recommend to check the citations and their position in the main text.

2. Another note concerns the figures. For a better understanding and legibility of the article, I would add at least one summary figure for each point, also taken from the cited articles, especially for those describing molecular mechanisms, or create figures that are also similar in concept to figure 1 on page 5, being very summary.

Author Response

Dear Sir or Madam, thank You very much for the review of the manuscript entitled: “Links between COVID-19 and Alzheimer’s disease – what we already know?”.

In response to Your comments, we would like to thank You for appreciating our manuscript.

Manuscript changes are highlighted in yellow.

 

Comment 1

In general, I think it would be preferable not to use the form "One study described ..." (page 7, line 316) or "Another study also reported ..." (page 7, line 317) to indicate certain works or results that you want to introduce into the discussion, above all, as in the specific case as an example, if the study is not cited (missing citation?).I therefore suggest that these sentences be replaced where necessary in the article with the name of the author, or group, followed by the appropriate citation.

Revision and my comment

In our opinion such forms (“one study described” or “another study also reported”) are correct and add clarity to the text. Concerning the specific case which You mentioned in Your comment, the citation is provided (line 345, reference no. 124).

 

Comment 1.1

Citations missing, or not directly identifiable, appear to be on page 4, lines 162 and 173, for point 4.1. “Overlaps between ACE2 and COVID-19” and page 7, line 317 for point 7.1. "Neuropsychiatric symptoms and cognitive decline". I recommend to check the citations and their position in the main text.

Revision and my comment

A citation for the text in the line 162 is provided (line 178 in the new version, reference no. 52). A reference for the text cited in the line 173 is now added (line 186, reference no. 57). Concerning the paragraph 7.1. "Neuropsychiatric symptoms and cognitive decline", we don’t see any unclear or missing citations.

 

Comment 2

Another note concerns the figures. For a better understanding and legibility of the article, I would add at least one summary figure for each point, also taken from the cited articles, especially for those describing molecular mechanisms, or create figures that are also similar in concept to figure 1 on page 5, being very summary.

Revision and my comment

Due to the character of certain paragraphs it is not always possible to create a figure based on them. However, we summarized all key findings mentioned in this article in graphical abstract.

 

We do honestly hope that it will satisfy You and improve the quality of our work. Once again we are very grateful for Your review and remain open if You have any other remarks or suggestions that will make our work merit publication in “International Journal of Environmental Research and Public Health”.

Sincerely,

Paulina Drożak on behalf of the authors

 

Reviewer 4 Report

The article is well written. I really like the structure of the article. I would suggest improving the figures, simplifying them, to make the article easier to read and understand. 

It would be also nice, given that neuroinflammation and oxidative stress are common features of other pathologies like PD, to include something about other neurodegenerative diseases and COVID19 at this level.  

 

Author Response

Dear Sir or Madam, thank You very much for the review of the manuscript entitled: “Links between COVID-19 and Alzheimer’s disease – what we already know?”.

In response to Your comments, we would like to thank You for appreciating our manuscript.

Manuscript changes are highlighted in yellow.

Comment 1

The article is well written. I really like the structure of the article. I would suggest improving the figures, simplifying them, to make the article easier to read and understand.

Revision and my comment

To clarify the figure, an explanation of the arrows and lines was added in the description under the Figure 1. Also, a brief description of the role of ACE2 receptor was added (lines 204-210).

 

Comment 2

It would be also nice, given that neuroinflammation and oxidative stress are common features of other pathologies like PD, to include something about other neurodegenerative diseases and COVID19 at this level. 

Revision and my comment

Studies concerning other neurodegenerative disorders (such as Parkinson’s disease or amyotrophic lateral sclerosis) and COVID-19 were mentioned in the Introduction section (lines 79-90).

 

We do honestly hope that it will satisfy You and improve the quality of our work. Once again we are very grateful for Your review and remain open if You have any other remarks or suggestions that will make our work merit publication in “International Journal of Environmental Research and Public Health”.

Sincerely,

Paulina Drożak on behalf of the authors