Overview of Memory NK Cells in Viral Infections: Possible Role in SARS-CoV-2 Infection

Round 1

Reviewer 1 Report

In this review the authors through an overview of NK memory cells in viral infections, described the possible role in SARS COV-2 infection. Particularly the authors described in exhaustive mode the involvment of NK cells in control of some viral infections, specifying their role and molecular mechanisms. Regarding the role of NK memory cells in SARS COV-2 infection, on the basis of recent literature studies, De Sanctis and collaborators describe the probably mechanisms trougth wich the activation of NK memory cells they would  play an essential role in eliminating virally infected cells. However for the resolution of the SARS CoV-2 pandemic, appears  essencial investigate and address much more complex aspects including the specific involvment of NK memory cells. The review is written in fluid and understandable English and the topic of great scientific interest. Authors are invited to check for any grammatical and/or typing errors. Concerning my revision, the review can be considered acceptd.

Author Response

We would like to thank the reviewer for the comments on the manuscript. The review now includes two figures to further document the different NK cell populations and the response to antigen and other receptors. We consider the manuscript now complete. 

Reviewer 2 Report

Please see attachment.

Comments for author File: Comments.pdf

Author Response

We would like to thank the reviewer for taking the time to write a detailed analysis of the manuscript and give important guidelines. The manuscript was thoroughly revised, the title was changed, new references were added, two figures were added to further illustrate the different NK cell subpopulations and the signal transduction involved in Nk cell activation. We added the figures to enhance the introduction. The part of SARS CoV2 infection and therapy was modified as suggested. The changes were highlighted in yellow. 

Reviewer 3 Report

 In this manuscript the authors present a review of role of NK cells in viral infections with a particular emphasis in SARS-Cov-2 infection. The list of NK cell role is accurate and actualized with information on how NK cells control the viral infection. The review can benefit from a more concise and focused abstract . The review will indulge the reader better with more organization and small headings for SARS-Cov-2 part ex: the potential of NK cells in viral infections and how the dysfunction of NK cells affects the SARS-Cov-2 infection, Immunotherapy options, and so on.

Although we remain in the early phases of filling the knowledge gap, some unique characteristics of the SARS-Cov-2 infection have begun to be consistently identified. These include the hyper-inflammatory response and cytokine storm associated with the disease as well as the contribution of NK cells to this hyper-inflammatory response. This should be mentioned in the review for better understanding.

Nonetheless, it may be naïve to assume that simply restoring memory NK cell numbers among COVID-19 patients will be sufficient to control the infection. The review can be improved by stressing the plasticity of NK cells and how it can be made anti-inflammatory along with the memory response.

Minor comments:

SARS CoV-2 disease severity seems to be associated with NKG2D expression and 259 high perforin and granzyme B levels in CD56 bright NK cells with COVID severity

            The sentence is a repeat, please change.

Author Response

We would like to thank the reviewer for the suggestions raised. The manuscript title was changed, we added two figures, modified several non-clear parts of the text and added new references. The changes were highlighted in yellow.

Round 2

Reviewer 2 Report

According to me, now the review will be ready for publication. Some minor suggestions are listed below:

Line 70

Please correct Nk with NK.

I appreciate a lot the new figures included: Figure 1 and Figure 2. They are clear and well depicted as well as very simple to understand. 

Lines 97

The same of Line 70.

I appreciate a lot that the authors reorganize the paragraph 3.

Line 355

Please indicate the references.

Author Response

We would like to thank the reviewer for his valuable comments. The changes in the manuscript are highlighted in yellow.