Experts make weak recommendation for remdesivir in severe COVID-19

In The BMJ today, a panel of international experts make a weak recommendation for the use of remdesivir in patients with severe covid-19, and strongly support continued enrolment of patients into ongoing clinical trials of remdesivir.

Their advice is part of The BMJ‘s Rapid Recommendations initiative—to produce rapid and trustworthy guidelines for clinical practice based on new evidence to help doctors make better decisions with their patients.

The antiviral medication remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19 and is already being used in clinical practice.

Today’s recommendation is based on a new evidence review comparing the effects of several drug treatments for covid-19 up to 20 July 2020.

It shows that remdesivir may be effective in reducing recovery time in patients with severe covid-19, although the certainty of the evidence is low. But remdesivir probably has no important effect on the need for mechanical ventilation and may have little or no effect on length of hospital stay.

The authors stress that “the effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.”

After thoroughly reviewing this evidence, the expert panel says that most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement.

But given the low certainty evidence, and allowing for different patient perspectives, values, and preferences, they issued a weak recommendation with strong support for continued recruitment in trials.

They suggest that future research should focus on areas such as optimal dose and duration of therapy, and whether there are specific groups of patients most likely to benefit from remdesivir.

The authors also sound a note of caution about the potential opportunity cost of using remdesivir while the evidence base is still uncertain. As a relatively costly drug that is given intravenously, use of remdesivir may divert funds, time, attention, and workforce away from other potentially worthwhile treatments.

The study that today’s recommendation is based on is called a living systematic review.

In a linked editorial, The BMJ editors explain that living systematic reviews are useful in fast moving research areas such as covid-19 because they allow authors to update previously vetted and peer reviewed evidence summaries as new information becomes available.

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Coronavirus: Physical distancing may help ease burden on hospitals, but only to a point

Scientists have found that longer periods of social distancing alone are not successful when it comes to slowing COVID-19 spread, an advance which may help make better decisions in countries where a second wave of the pandemic is expected.

“Conventional wisdom was, the more intense and long-term the social distancing, the more you will curb the disease spread,” said Rajan Chakrabarty, a co-author of the study from Washington University in St. Louis in the US.

According to the study, published in the journal Chaos, any strategy that involves social distancing requires other steps be taken in tandem.

“But that is true if you have social distancing implemented with contact tracing, isolation and testing. Without those, you will give rise to a second wave,” Chakrabarty said.

Payton Beeler, another co-author of the study, noted that if social distancing is the only measure taken, it must be implemented extremely carefully in order for its benefits to be fully realized.

Their epidemiological model used data gathered by Johns Hopkins University in the US between March 18 and March 29, a period marked by a rapid surge in COVID-19 cases and the onset of social distancing in most US states. Calibrating the model using these datasets allowed the authors to analyse unbiased results that had not yet been affected by large-scale distancing in place, they said.

The model also included details on how much people of different age groups interact, and how that affects the spread of transmission.

“Had social distancing been implemented earlier, we probably would’ve done a better job,” Chakrabarty said.

Over the short-term, more distancing and less hospital demand go hand in hand, the scientists said, adding that this is only up to two weeks. After that, they said the time spent distancing does not benefit hospital demand as much. Society would have to increase social distancing time exponentially in order to see a linear decrease in hospital demand, the researchers noted.

They said this leads to diminishing returns. Society would see smaller and smaller benefits to hospital demand the longer it spent social distancing, the scientists explained.

According to the researchers, if social distancing “alone” is to be implemented longer than two weeks, a moderate shut down, say between 50-70 per cent, could be more effective for the society than a stricter complete shut-down in yielding the largest reduction in medical demands.

Another strategy for flattening the curve involves acting intermittently, alternating between strict social distancing and no distancing to alleviate the strain on hospitals, the study noted. According to the model, the most efficient distancing- to- no-distancing ratio is five to one, meaning one day of no distancing for every five days at home. Had society acted in this way, the researchers said the hospital burden could have been reduced by 80 per cent. “Bending the curve using social distancing alone is analogous to slowing down the front of a raging wildfire without extinguishing the glowing embers,” said Chakrabarty.

“They are waiting to start their own fires once the wind carries them away,” he said, adding however that his team’s model cannot inform strategies going forward as it used data collected in March. But Chakrabarty added that it may be able to inform our actions if we find ourselves in a similar situation in the future.

“Next time, we must act faster, and be more aggressive when it comes to contact tracing and testing and isolation,” Chakrabarty said.

(This story has been published from a wire agency feed without modifications to the text. Only the headline has been changed.)

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