麻豆传媒

About two-thirds of severe COVID-19 coronavirus patients treated with the investigational antiviral agent remdesivir showed clinical improvement, researchers found.

But by the same token, about one-third did not -- including seven who died, out of the first 53 patients receiving remdesivir as "compassionate use" for whom data were analyzed.

In that group, , reported Diana Brainard, MD, of drugmaker Gilead Sciences, and colleagues in the New England Journal of Medicine.

With median follow-up of 18 days, overall mortality was 13%. Among those receiving invasive ventilation, 18% died (n=6). Mortality was 5% (n=1) among those not receiving invasive ventilation, Brainard and colleagues wrote.

Mean interval between initiation of remdesivir and death in the fatal cases was 15 days.

On the plus side, 17 of 30 patients receiving mechanical ventilation were extubated, and three of four receiving extracorporeal membrane oxygenation (ECMO) were removed from it, all surviving at last follow-up.

This was an observational report on the initial cohort of patients receiving the drug as compassionate use, and thus there was no control group.

"To date, no therapy has demonstrated efficacy in patients with COVID-19," the authors wrote. "Although data from several ongoing randomized, controlled trials will soon provide more informative evidence regarding the safety and efficacy of remdesivir for COVID-19, the outcomes observed in this compassionate use program are the best currently available clinical data."

The authors lacked data on viral load, and they were limited by the small sample size of their trial, short follow-up, and absence of a control group. Nevertheless, they concluded, "comparisons with contemporaneous cohorts from the literature ... suggest that remdesivir may have clinical benefit in patients with severe COVID-19."

Brainard and colleagues added that ongoing randomized, placebo-controlled trials of remdesivir therapy for COVID-19 will provide a better picture of the drug's effectiveness.

Remdesivir has been explored as a potential therapy for COVID-19 since the earliest days of the outbreak, and the company began accepting requests for compassionate use on Jan. 25, the authors said. The drug has broad-spectrum in vitro activity against coronaviruses, such as SARS-CoV and MERS-CoV, and filoviruses like Ebola, although previous clinical trials showed it was largely ineffective against Ebola infection in humans.

In the COVID-19 study, patients had confirmed SARS-CoV-2 infection and oxygen saturation of 94% or less while breathing ambient air or receiving oxygen support. They received a 10-day course of remdesivir.

Overall, 61 patients received at least one dose of remdesivir on or before March 7, with eight excluded due to missing baseline information. Twenty-two of these patients were in the U.S., 12 in Italy, nine in Japan, and four in France.

Three-quarters of the 53 patients received the full course of the drug. Patients ranged in age from 23 to 82, with a median age of 64, and about three-quarters were men.

Researchers noted that at baseline 34 patients were receiving invasive ventilation, with 30 receiving mechanical ventilation and four receiving ECMO. Median duration of invasive mechanical ventilation prior to treatment was 2 days.

Median duration of symptoms prior to receiving remdesivir was 12 days, and researchers added this did not differ between patients receiving invasive and non-invasive ventilation.

While the majority of patients showed improvement in oxygen supply, eight patients got worse. All 12 patients breathing ambient air or who received low-flow supplemental oxygen and five of seven patients receiving high-flow supplemental oxygen showed improvement as well.

At last follow-up, 47% of patients had been discharged, including eight of 34 receiving invasive ventilation and 17 of 19 receiving non-invasive oxygenation support. However, clinical improvement was less frequent in patients receiving invasive ventilation versus non-invasive ventilation, and patients age 70 or older versus those younger than age 50 -- in general, the patients with the poorest prognosis based on currently known risk factors.

Examining safety, 32 patients reported adverse events during follow-up, the authors noted, with the most common being increased hepatic enzymes, diarrhea, rash, renal impairment, and hypotension. Not surprisingly, these events were more common among patients receiving invasive ventilation. Twelve patients with serious adverse events, including multiple organ-dysfunction syndrome, septic shock, acute kidney injury, and hypotension, received invasive ventilation at baseline.

Four patients discontinued treatment prematurely, two because of elevated aminotransferases, one due to preexisting renal failure, and one due to multiple organ failure.

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