Clinical Outcomes and Survival Analysis of Remdesivir as a Treatment Option for Moderate to Severe COVID-19 Patients

Round 1

Reviewer 1 Report

 Aboelsaad et al assessed the  effect of Remdesvir (RDV) in Covid-19 moderate and sever cases. The beneficial effect of RDV is controversial and several reports are debatably controversial. However, more studies are definitively needed to confirm as the drug is expensive. Studying patients in a single center facility, they concluded that RDV does not have significant effect on mortalities, ventilation use and transfer to higher level.  This paper is acceptable for publication with some modifications.

1.Patients generally was admitted in hospital at different conditions. How the measure of days are calculated? The significant differences of 8 days vs 9 days after admission is very little although authors concluded that there is no RDV effect but they should explain briefly in the results or discussion that this differences may not be valid or compounded.

2.The RDV and NoRDV group also used some other antiviral drugs, it is not perfect RDV/NoRDV comparisons. Although it is written to “a comparison of RDV is conducted against a combination of antivirals and standard care” but both the group should have antivirals. “against” should be “with. These should be explained more.

3. Is there any gender specific effect observed?

4. There are some mistakes in English that should be corrected. Few examples are below.

5. In abstract “in the RDV group (8 days) than” repeated.

6. In key words, “and” should be omitted and “treatment”,  “clinical outcome” or else will be better than “covid-19 treatment”

7.Table 4 should be Table 3 in the text.

8. All supplementary tables should be designated similarly in the text (S2).

9. Authors should provide ethical statement/approval to carry out the work.

Author Response

First, we appreciate your valuable and constructive feedback, and let's discuss point-by-point comments.

Comments and Suggestions for Authors

 Aboelsaad et al assessed the  effect of Remdesvir (RDV) in Covid-19 moderate and sever cases. The beneficial effect of RDV is controversial and several reports are debatably controversial. However, more studies are definitively needed to confirm as the drug is expensive. Studying patients in a single center facility, they concluded that RDV does not have significant effect on mortalities, ventilation use and transfer to higher level.  This paper is acceptable for publication with some modifications.

1.Patients generally was admitted in hospital at different conditions. How the measure of days are calculated? The significant differences of 8 days vs 9 days after admission is very little although the authors concluded that there is no RDV effect but they should explain briefly in the results or discussion that this differences may not be valid or compounded.

We really wrote this in the results section [ line 187- 190, 192-196]:

“patients in the RDV group had statistically significant shorter hospital length of stay (median= 8 [range 1-29] days) than patients in the NoRDV group (median = 9 [ range 1-65] days) (P= 0.004), and the difference was more evident in severe cases”.

“Death, MV, and transfer to a higher level were the primary composite outcomes in 17.7 % of the RDV group and 22 % of the non-RDV group. However, the effect was statistically insignificant (p-value 0.289)”

2.The RDV and NoRDV group also used some other antiviral drugs, it is not perfect RDV/NoRDV comparisons. Although it is written as “a comparison of RDV is conducted against a combination of antivirals and standard care” both the group should have antivirals. “against” should be “with. These should be explained more.

Indeed only 11 patients took another antiviral drug (lopinavir/ritonavir) in the Non-RDV group and this was statistically insignificant we added this number and percentage to the S6 table.

3. Is there any gender specific effect observed?

We didn’t find any statistically significant difference regarding gender. Females represent 55.4% of the NoRDV group and 46.9% of the RDV group.

4. There are some mistakes in English that should be corrected. Few examples are below.
5. In abstract “in the RDV group (8 days) than” repeated.

We deleted the repetition

6. In key words, “and” should be omitted, and “treatment”, and “clinical outcome” or else will be better than “covid-19 treatment”

Done

7.Table 4 should be Table 3 in the text.

Done

8. All supplementary tables should be designated similarly in the text (S2).

All supplementary tables are reformulated and unified in text like table S2.

9. Authors should provide ethical statement/approval to carry out the work.

The ethical approval statement was mentioned on line 320

Author Response File: Author Response.docx

Reviewer 2 Report

Reviewer’s Comments

In the study titled ‘Clinical outcomes and survival analysis of Remdesivir as a treatment option for moderate to severe COVID-19 patients’ the authors Aboelsaad et al. have done a single-center retrospective study on 509 PCR-confirmed COVID-19 patients. Out of these 509 patients, 35% of the patients received RDV. There was a marginal benefit in the median hospital length of stay and composite outcome for the RDV-treated group. However, there was no difference in in-hospital death, mechanical ventilation, Transfer to higher level and mortality rate between RDV-treated and untreated groups.

The study can support decision-making bodies on the recommendation of RDV for COVID-19 patients. However, there are a few published reports of the beneficial effects of RDV for COVID-19 patients. The availability of the COVID vaccine has slowdown the efforts of validating RDV. In this manuscript, the authors explain the limitations of their study.

There needs an improvement in the writing part of the manuscript. Here are a few suggestions which might improve the manuscript.

1. Need to define the ‘severe patients’
2. RDV group had 64% severe patients. Were there any severe patients in the NoRDV group? If yes, what was the percentage?
3. Introduction: Line2-3: 30th January ………. Include year
4. The authors may consider rephrasing the sentence in Abstract results: In contrast, the median hospital length of stay in the RDV group was lower (8 days) than in the RDV group (8 days) than the NoRDV (9 days),
5. The authors may consider including the article PMID: 34699552, which reports the beneficial effect of early administration of RDV. 

Author Response

we appreciate your valuable and constructive feedback, and let's discuss point by point comments:

Reviewer’s Comments

In the study titled ‘Clinical outcomes and survival analysis of Remdesivir as a treatment option for moderate to severe COVID-19 patients’ the authors Aboelsaad et al. have done a single-center retrospective study on 509 PCR-confirmed COVID-19 patients. Out of these 509 patients, 35% of the patients received RDV. There was a marginal benefit in the median hospital length of stay and composite outcome for the RDV-treated group. However, there was no difference in in-hospital death, mechanical ventilation, Transfer to higher level and mortality rate between RDV-treated and untreated groups.

The study can support decision-making bodies on the recommendation of RDV for COVID-19 patients. However, there are a few published reports of the beneficial effects of RDV for COVID-19 patients. The availability of the COVID vaccine has slowdown the efforts of validating RDV. In this manuscript, the authors explain the limitations of their study.

There needs an improvement in the writing part of the manuscript. Here are a few suggestions which might improve the manuscript.

1. Need to define the ‘severe patients’

Actually, we define moderate and severe covid in the methodology section according to MoHP protocol, in the inclusion criteria section, line [131 -133].

“Patients with moderate COVID-19 had pulmonary infiltrates and SpO2 %, whereas severe COVID-19 patients had respiratory rate > 30 breaths/min or lung infiltrates > 50 and SpO2 < 92 %, PaO2/FiO2 < 300 (12,13)”.

1. RDV group had 64% severe patients. Were there any severe patients in the NoRDV group? If yes, what was the percentage?

Yes, it was mentioned in the result section line [ 172- 173]

 “One hundred ninety-seven patients (40.1% NoRDV, 36% RDV group) were identified as having moderate disease, and 312 (59.9% NoRDV, 64% RDV group) were in the severe disease stratum”.

1. Introduction: Line2-3: 30th January ………. Include year

Done (the year 2020)

1. The authors may consider rephrasing the sentence in Abstract results: In contrast, the median hospital length of stay in the RDV group was lower (8 days) than in the RDV group (8 days) than the NoRDV (9 days),

Done, repetition was deleted

1. The authors may consider including the article PMID: 34699552, which reports the beneficial effect of early administration of RDV.

Thanks for the suggestion, we added it to the discussion section “In 2021 Hussain Alsayed et.al. found that early administration of RDV (first 7 days of symptoms onset) could decrease ICU admissions (aHR 0.31; 95% CI, 0.15 to 0.64), MV need (aHR, 0.22; 95% CI, 0.10 to 0.51), and mortality at 28 days (aHR, 0.15; 95% CI, 0.04 to 0.53) than RDV late administration or non RDV group”

Author Response File: Author Response.docx