COVID19 update, April 17, 2020: Breaking (good) news about remdesivir; ventilators questioned again. UPDATE: UV-C irradiation as an antisepsis technique

A number of clinical trials are going on with the nucleotide analog remdesivir.

Remdesivir, a.k.a. GS-5734

Now news is breaking on various news sites that one of the clinical trials, on 125 patients at U. of Chicago Medical Center, showed great promise. The orginal report appears to come from the medical statistics website STATNEWS. Some quotes:

The University of Chicago Medicine recruited 125 people with Covid-19 into Gilead’s two Phase 3 clinical trials. Of those people, 113 had severe disease. All the patients have been treated with daily infusions of remdesivir. 

“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital. 

Her comments were made this week during a video discussion about the trial results with other University of Chicago faculty members. The discussion was recorded and STAT obtained a copy of the video.

[…]

Mullane, while encouraged by the University of Chicago data, made clear her own hesitancy about drawing too many conclusions.

“It’s always hard,” she said, because the severe trial doesn’t include a placebo group for comparison. “But certainly when we start [the] drug, we see fever curves falling,” she said. “Fever is now not a requirement for people to go on trial, we do see when patients do come in with high fevers, they do [reduce] quite quickly. We have seen people come off ventilators a day after starting therapy. So, in that realm, overall our patients have done very well.”

She added: “Most of our patients are severe and most of them are leaving at six days, so that tells us duration of therapy doesn’t have to be 10 days. We have very few that went out to 10 days, maybe three,” she said. 

There was anecdotal evidence from the start that remdesivir — originally developed for ebola, and previously shown to be active in vitro (i.e., in the test tube) against coronaviruses — was effective in at least some COVID19 patients. There were two early cures during the Washington state outbreak, and in Israel, “patient #16”, a tour bus driver who got severely ill after ferrying a group of infected pilgrims around for days, quickly recovered when given the drug as a last resort. Also, last week, a small trial was published in the prestigious New England Journal of Medicine.

Unlike the several mechanisms proposed for hydroxychloroquine, the mechanism by which remdesivir works is clearly understood and unambiguous. In plain English, the drug [*] pretends to be the letter A of the genetic alphabet, but when the enzyme RdRa (RNA-dependent RNA polymerase) starts making copies of the virus RNA and it grabs the “fake A” instead of a real A (adenosine), the next letter has nowhere to go, and copying breaks off. (This is not something I can see an easy way for the virus to quickly mutate-and-evolve its way into resistance for: making RdRa so clever it can tell the difference between real A and fake A? Developing an enzyme that selectively “eats” the fake A?)

The theory sounds good, and was confirmed in the test tube and in an “animal model” (in this case, rhesus monkeys): but many drug candidates that ticks all the boxes in the lab fall flat when administered to actual human patients. Fortunately, testing for safety and side effects in humans had already been completed years ago, when Gilead Sciences first tried to obtain FDA approval for its use in ebola. Thus, clinical trials could skip these steps and immediately proceed to actual clinical effectiveness tests.

I am looking forward to the final public release of data, but this looks quite promising.

Elsewhere on STATNEWS, I found another story reviewing the evidence (some of it covered here in earlier updates) about ventilators in a COVID19 setting, and how in many cases noninvasive respiration appears to be the preferred alternative. Read the whole thing.

In the US, President Trump has unveiled a staged “Opening Up America Again” plan (full text available at the link). The plan is attacked by some as being too timid and laying out unrealistic threshold conditions . Others say that it reflects a compromise between epidemiological and economic imperatives. We link, you decide.

Finally, Israeli PM Benjamin “Bibi” Netanyahu signed off in principle on a staged plan for reopening the Israeli economy, to be voted on in a cabinet meeting tomorrow night.

Unless important news breaks tomorrow, I will probably skip updates on the sabbath. Shabbat shalom, and to the Eastern Orthodox Christian readers, a meaningful Good Friday and a happy Easter. And to all: stay healthy and safe!

[*] technically, remdesivir is what pharmacologists call a prodrug, i.e., a molecule that within the body reacts to release the active drug component.

UPDATE: Dr. Seheult on remdesivir and on a novel approach to keeping hospital rooms and public spaces sterile: far UV-C lamps. UV-C light is the type of “hard” UV radiation that is blocked by the earth’s ozone layer. Far UV-C (207-222nm) is high enough energy to destroy bacteria and viruses, but too short-waved to penetrate further than the top layer of cells — therefore does not cause skin cancer or cataracts.