Remdesivir in the treatment of COVID-19

In the last weeks, some studies have been published on the efficacy of remdesivir in the treatment of COVID-19 infection.

The results are quite contrasting. Only two of these studies have been performed with a randomized controlled design. The others are observational studies. Substantially negative results emerge from one of the two randomized studies, while extremely positive effects appear to be emerging from the others.

Remdesivir in the treatment of COVID-19: inhibiting viral replication

Remdesivir developed from a collaboration between Gilead Sciences, the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID).

The aim was to identify therapeutic agents for the treatment of RNA-based viruses with global pandemic potential.

Remdesivir is a prodrug which is metabolized intracellularly in an adenosine triphosphate analogue, capable of inhibiting viral RNA polymerase. It has a broad antiviral spectrum including filoviruses, such as Ebola, paramyxovirus, pneumovirus and coronavirus.

In vitro, remdesivir inhibits all human and animal coronaviruses tested, including SARS-CoV-2, and has shown antiviral activity and clinical effects in animal models of SARS-CoV-1 and Middle Eastern respiratory syndrome (MERS).

In an animal model of SARS-CoV-2, early administration of remdesivir revealed significant antiviral and clinical effects.

Remdesivir in the treatment of COVID-19: an observational study

An observational study published in June in the New England Journal of Medicine highlights a possible efficacy of remdesivir in the treatment of COVID-19 disease.

Although it is not a clinical trial, the results of the study show high percentages of patients who benefit from this drug.

In this research, the authors treated on a compassionate basis 53 patients with confirmed SARS-CoV-2 infection who had 94% or less oxygen saturation in ambient air or received oxygen. They were treated with a 10-day cycle of remdesivir (200 mg administered intravenously on day 1, followed by 100 mg per day for the remaining 9 days of treatment).

During a median 18-day follow-up, 68% of patients experienced improvement. The fifty-seven percent of mechanically ventilated patients were extubated. The 13% of the patients died, with a mortality of 18% in patients who received invasive ventilation and 5% among those who did not.

The authors conclude by stressing the high percentage of patients who had an improved, but admit the need for randomized, placebo-controlled clinical trials.

Remdesivir in the treatment of COVID-19: a negative study

The first randomized controlled trial on remdesivir that we want to present to you was published last April in the journal The Lancet.

The trial took place in ten hospitals in Hubei, China. Patients included in the study were hospitalized with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrollment of 12 days or less. Their oxygen saturation was less than or equal to 94% in ambient air.

The two treatment groups included intravenous remdesivir (200 mg on day 1, followed by 100 mg on days 2–10, in single daily infusions) or the same volume of placebo infusions for 10 days.

The rate of clinical improvement was greater in patients on active treatment, but unfortunately did not reach statistical significance.

Adverse events were reported in 66% of remdesivir-treated patients and 64% of control subjects.

In this study, the authors conclude that remdesivir was not associated with statistically significant clinical benefits. They emphasize that the faster rate of clinical improvement in those treated earlier requires confirmation in larger studies.

Remdesivir in the treatment of COVID-19: a positive study

The second randomized study that we propose to your attention was published in late May in the New England Journal of Medicine.

The study was conducted with a double-blind, randomized, placebo-controlled design on 1,063 patients. The final analysis included data from 1,059 of them, who were randomly assigned to receive remdesivir (loading dose of 200 mg on day 1, followed by 100 mg per day for up to 9 additional days) or placebo for a maximum of 10 days.

The results quickly became so important that the data and safety monitoring committee recommended their immediate publication. The patients who had received remdesivir had a median recovery time of 11 days, compared to 15 days in the control group.

The 14-day mortality estimates were 7.1% in remdesivir-treated patients and 11.9% in control subjects.

Serious adverse events in the two active treatment and control groups occurred with percentages of 21.1% and 27% respectively.

In this case the authors express no doubts, highlighting that thanks to remdesivir the recovery time in adults hospitalized with Covid-19 has been significantly reduced.

Remdesivir in the treatment of COVID-19: final considerations

Looking at the different experiments published on the topic, data in favor of treatment with remdesivir in patients with COVID-19 seem to emerge.

However, despite the frantic search for an effective treatment against the disease, it should be noted that the use of this drug has been evaluated in these studies only in terms of speed of healing times. Nothing can be said about survival.

With the increase in the number of COVID-19 cases, other experiments concerning remdesivir are to be expected. We hope they will bring other useful information, clarifying what is the best moment to start the treatment. How early it can and should be started to obtain more benefits.

It should also be noted that despite the use of remdesivir, or other antiviral agents, disease mortality remains high. Therefore, the use of these drugs does not seem sufficient to combat completely and effectively SARS-CoV-2 infection.

 

This post is also available in: Chinese (Simplified)

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