Severe Acute Respiratory Syndrome Coronavirus-2 Delta Variant Study In Vitro and Vivo

Round 1

Reviewer 1 Report

In this manuscript, Avagyan et al., investigated the pathogenesis caused by SARS-CoV-2 Delta variant. They showed that SARS-CoV-2 in Syrian hamsters causes a short-term pulmonary form of the disease. They also confirmed the pathogenesis in the blood and bone marrow. The data is interesting because they tested the infectivity of Delta variant both in vitro and vivo. However, I have both major and minor comments for this manuscript.

Major

1.     Line 178-179: The authors described that “staining reveals significant changes in virus-infected cells compared to control”. However, it is difficult to see the difference between Figure2A and B. The authors should explain what is the major difference between figure 2A and B.

2.     Line 188: Figure legend 2A and B are same. B should be “infected”.

3.     Line 306: The authors describe that “the lungs are enlarged”. However, it is difficult to see the difference only by picture. The authors need to show the evidence by weight change or size between uninfected sample. 

4.     Line185-186: there are no explanation about Figure 1E. Please add it.

5.     Figure 4A, B, C: The authors should describe what Y-axis means.

6.     Figure 7A: “Control Virus” doesn’t make sense. This should be “Virus infected”.

7.     Line 343: The authors described that “the content of resident macrophages in lymph nodes increases”. Did the authors count the numbers of macrophages?  If the authors say “increased”, they should show the data with statics analysis.

8.     Do the authors think these pathogeneses which were shown in the manuscript (both in vitro and vivo) are specific to SARS-CoV-2 Delta variant? If they have some data from SRAS-CoV-2 WA/2020 or other variants, it is much better. If not, they should cite previous paper and need to discuss more in the “Discussion”.

Minor

1.     Figure 4C-X axis: 8-dpi is duplicate. Please fix it. 

2.     Table 2-the first lane: “SARS-CoV-XXdpi” should be “SARS-CoV-2-XXdpi” 

3.     Line 176: “hours after infection (hpi)” should “hours post infection (hpi)”

4.     Words must uniform through the manuscript. For example: “RT-PCR or qRT-PCR”.  “Figure 7A-X-axis should be show as dpi”.

5.     Line 198: typo “snd”

Author Response

Major

1. Line 178-179: The authors described that “staining reveals significant changes in virus-infected cells compared to control”. However, it is difficult to see the difference between Figure2A and B. The authors should explain what is the major difference between figure 2A and B

 This is our mistake and figures showing changes in virus-infected cells compared to control have been added in the manuscript.

Instead of this “Hematoxylin-eosin staining reveals significant changes in virus-infected cells compared to control (Fig 2 A, B). ”

Should be this “Hematoxylin-eosin staining reveals significant changes in virus-infected cells (Fig 2C, D, E, F) compared to control (Fig 2 A, B). ”

Line 188: Figure legend 2A and B are same. B should be “infected”.

This mistake has been explained above (comments 1). Figure 2A and 2B are the same and show mock infected cells (control). Virus-infected cells are shown in Fig. 2 C, D, E, F.

2. Line 306: The authors describe that “the lungs are enlarged”. However, it is difficult to see the difference only by picture. The authors need to show the evidence by weight change or size between uninfected sample. 

Fig. 8. And correspond legend for F and G have been replaced.

3. Line185-186: there are no explanation about Figure 1E. Please add it.

Corresponded explanation has been added in the main document.

5. Figure 4A, B, C: The authors should describe what Y-axis means.
6. Figure 7A: “Control Virus” doesn’t make sense. This should be “Virus infected”.

Comment  6  is unclear. In the explanation of Figure 7A, both in results section 3.5 and in legend 7A, there is no such concept as "Control virus". There is only Control (healthy animal)

7. Line 343: The authors described that “the content of resident macrophages in lymph nodes increases”. Did the authors count the numbers of macrophages?  If the authors say “increased”, they should show the data with statics analysis.

Corresponded data has been added in the manuscript. 

8. Do the authors think these pathogeneses which were shown in the manuscript (both in vitro and vivo) are specific to SARS-CoV-2 Delta variant? If they have some data from SRAS-CoV-2 WA/2020 or other variants, it is much better. If not, they should cite previous paper and need to discuss more in the “Discussion”.

Corresponded data has been added in the Discussion section of manuscript. 

Minor

1. Figure 4C-X axis: 8-dpi is duplicate. Please fix it. 

Corresponding change has been made.

2. Table 2-the first lane: “SARS-CoV-XXdpi” should be “SARS-CoV-2-XXdpi” 

Corresponding change has been made.

3. Line 176: “hours after infection (hpi)” should “hours post infection (hpi)”

Corresponding change has been made.

4. Words must uniform through the manuscript. For example: “RT-PCR or qRT-PCR”.  “Figure 7A-X-axis should be show as dpi”.

Corresponding change has been made.

5. Line 198: typo “snd”

Corresponding change has been made.

Reviewer 2 Report

Must improve quality presentation of histological results !

Choose more representative images !

Author Response

Some changes of figures (Fig. 9 and Fig. 10) and discussion section  was made In the manuscript. 

Round 2

Reviewer 1 Report

In the authors response, they said that they improved the manuscript according to my review point. However, I didn’t see any changes in the uploaded file. It looks like the authors uploaded old version. Please upload the new version.
Also, now it looks like the Figure number is messed up (Fig.5-7). Please check the order carefully and fix them. 

Author Response

Some changes was made.