Revisiting the COVID-19 Pandemic: An Insight into Long-Term Post-COVID Complications and Repurposing of Drugs
, Swagata Roy Chowdhury 1, Abinit Saha 1 and Rudra P. Saha 1,*
Round 1
Reviewer 1 Report
In this interesting review, the authors have discussed COVID-19 from several aspects, including Post COVID complications, the immunological changes in long COVID, possible treatments based on drug remodeling through in silico studies and clinical trails, and the use of nutraceuticals to enhance immunity and protect against long COVID.
The review is nicely written, however, I have some comments that may help improve the manuscript:
1. The paragraph 178-181 seems irrelevant or incomplete. It describes the alveolar wall composition, but no further data are added to link this description with the respiratory complications caused by SARS-CoV2.
2. The paragraph 182-192 seems misplaced. It is more suitable to be included in the introduction.
3. Numbering of references should be revised. The references is table 1 should be numbered successively starting directly with the number after the last reference in the previous paragraph [i.e. 29].
4. The language, style and format of the manuscript should be thoroughly revised.
5. Some abbreviations were used without mentioning the full term at all. (e.g. line 245; PTSD, line 294; LH, line 332; TCR, line 413; POTS, line 485; GPCRs).
6. Line 548: Virus entry blockers is repeated twice. Please revise and correct.
7. In the conclusion, a paragraph that sums up the whole article briefly is required.
Author Response
Reviewer 1:
In this interesting review, the authors have discussed COVID-19 from several aspects, including Post COVID complications, the immunological changes in long COVID, possible treatments based on drug remodeling through in silico studies and clinical trails, and the use of nutraceuticals to enhance immunity and protect against long COVID.
The review is nicely written, however, I have some comments that may help improve the manuscript:
Comment: We'd like to thank you for taking the time to carefully look over this manuscript. Your suggestions have helped to improve the quality of the revised manuscript substantially. All the changes made to the revised manuscript are in track change mode.
1. The paragraph 178-181 seems irrelevant or incomplete. It describes the alveolar wall composition, but no further data are added to link this description with the respiratory complications caused by SARS-CoV2.
Comment: We would like to thank you for your valuable suggestion. We have revised the section as advised.
2. The paragraph 182-192 seems misplaced. It is more suitable to be included in the introduction.
Comment: We have now moved the paragraph into the introduction section.
3. Numbering of references should be revised. The references is table 1 should be numbered successively starting directly with the number after the last reference in the previous paragraph [i.e. 29].
Comment: All reference numbers have been revised as suggested.
4. The language, style and format of the manuscript should be thoroughly revised.
Comment: English corrections have been made extensively, and we hope the current version of the manuscript will be of acceptable quality.
5. Some abbreviations were used without mentioning the full term at all. (e.g. line 245; PTSD, line 294; LH, line 332; TCR, line 413; POTS, line 485; GPCRs).
Comment: A new abbreviations section has been added to the manuscript.
6. Line 548: Virus entry blockers is repeated twice. Please revise and correct.
Comment: Corrected.
7. In the conclusion, a paragraph that sums up the whole article briefly is required.
Comment: We have revised the conclusion section as per your suggestion.
Reviewer 2 Report
The review article brings interesting data and summarizes important features of post-COVID-19 syndrome. However, need further improvement for publication in COVID.
Major concerns:
-The paper has substantial punctuation and spacing errors, confused sentence construction, and needs English revision.
-It is difficult to follow and link the two main subjects of the review paper. There are 2 review articles, one talking about the Long COVID and its treatment and another review, beginning in section 4.1, showing drug repurposing, platforms for drug repurposing, and drugs used for acute COVID-19.
-Section 5 must be followed by a disclaimer. Nowadays, we must be very careful with some experimental data, especially when it can be used out of context to generate fake news. There is no robust evidence that an anti-inflammatory diet can treat long-COVID, especially when a myriad of events are involved. Also, fomenting the consumption of functional foods can produce adverse effects. For example, the consumption of vitamin D, there is evidence that Vitamin D has antiviral and immunomodulatory activity. However, during the pandemic, the massive consumption and overdose of vitamin D significantly increased adverse effects. Particularly I don´t think this section adds to the scientific discussion.
Author Response
Reviewer 2:
The review article brings interesting data and summarizes important features of post-COVID-19 syndrome. However, need further improvement for publication in COVID.
Comment: We'd like to thank you for taking the time to carefully look over this manuscript. Your suggestions have helped to improve the quality of the revised manuscript substantially. All the changes made to the revised manuscript are in track change mode.
Major concerns:
-The paper has substantial punctuation and spacing errors, confused sentence construction, and needs English revision.
Comment: English corrections have been made extensively, and we hope the current version of the manuscript will be of acceptable quality.
-It is difficult to follow and link the two main subjects of the review paper. There are 2 review articles, one talking about the Long COVID and its treatment and another review, beginning in section 4.1, showing drug repurposing, platforms for drug repurposing, and drugs used for acute COVID-19.
Comment: We have revised the manuscript as per your suggestion and tried to establish the link between these two important sections, the long COVID and the need for drug repurposing.
-Section 5 must be followed by a disclaimer. Nowadays, we must be very careful with some experimental data, especially when it can be used out of context to generate fake news. There is no robust evidence that an anti-inflammatory diet can treat long-COVID, especially when a myriad of events are involved. Also, fomenting the consumption of functional foods can produce adverse effects. For example, the consumption of vitamin D, there is evidence that Vitamin D has antiviral and immunomodulatory activity. However, during the pandemic, the massive consumption and overdose of vitamin D significantly increased adverse effects. Particularly I don´t think this section adds to the scientific discussion.
Comment: Thank you very much for pointing out this important issue. We do agree with your concern. Hence, we have revised this section as per your suggestion. We have also added some evidence based experimental studies supported by appropriate references.
Reviewer 3 Report
At least 65 million individuals worldwide have suffered from post-COVID-19 condition, which causes a public health concern. In this review, Majumder et al. provide a comprehensive summary of the short-term and long-term effects of COVID-19 on health issues, including the damage and side effects on the cardiovascular, respiratory, gastrointestinal tract, nervous systems, dermatological, renal, and gonadal systems, as well as immunological changes. The authors also systematically address the rationale and methods involved in drug repurposing of drugs in COVID-19 drug development. In addition, the article mentions how to prevent long COVID.
The overall summarization of the post-COVID-19 condition and drug repurposing has been clearly presented by the authors, although not all discussions are closely focused on the theme.
Minor issues
1. Since this review did not discuss the COVID-19 diagnosis, it would be better to avoid mentioning it in the abstract (line 26).
2. Some introductions are redundant and off-topic. For example, under the respiratory complications section, the paragraphs between lines 167 and 192 mentioned SARS-CoV-2 infection, alveolar wall, ACE2, and other coronaviruses; however, all of them deviated from the theme of this section: respiratory complications. As a result, the description will distract readers.
3. The authors offered beneficial and sufficient information to narrate drug repurposing. Unfortunately, these findings seem to pile here and need to be organized and exhibited well, in particular in the introduction part of this section.
4. Please check the newly released information about remdesivir. FDA approves Remdesivir as a COVID-19 treatment drug. https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals-including-antibody-products/remdesivir/
5. There are some grammar mistakes in the manuscript that could be improved.
Author Response
Reviewer 3:
The overall summarization of the post-COVID-19 condition and drug repurposing has been clearly presented by the authors, although not all discussions are closely focused on the theme.
Comment: We'd like to thank you for taking the time to carefully look over this manuscript. Your suggestions have helped to improve the quality of the revised manuscript substantially. All the changes made to the revised manuscript are in track change mode.
Minor issues
1. Since this review did not discuss the COVID-19 diagnosis, it would be better to avoid mentioning it in the abstract (line 26).
Comment: We have removed the specific keyword.
2. Some introductions are redundant and off-topic. For example, under the respiratory complications section, the paragraphs between lines 167 and 192 mentioned SARS-CoV-2 infection, alveolar wall, ACE2, and other coronaviruses; however, all of them deviated from the theme of this section: respiratory complications. As a result, the description will distract readers.
Comment: In response to your suggestions, we have revised the section.
3. The authors offered beneficial and sufficient information to narrate drug repurposing. Unfortunately, these findings seem to pile here and need to be organized and exhibited well, in particular in the introduction part of this section.
Comment: The introduction section and other parts have been revised accordingly.
4. Please check the newly released information about remdesivir. FDA approves Remdesivir as a COVID-19 treatment drug.
https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals-including-antibody-products/remdesivir/
Comment: We have incorporated the information related to remdesivir in the revised manuscript.
5. There are some grammar mistakes in the manuscript that could be improved.
Comment: English corrections have been made extensively, and we hope the current version of the manuscript will be of acceptable quality.
Round 2
Reviewer 2 Report
Doubts and questions were adequately answered and attended to. Now the manuscript can be accepted for publication.
