The Search for the Cure

Hydroxychloroquine failed.

Back in February and early March, doctors in Wuhan, China reported some promising results using it in some covid-19 patients. And a French doctor, Didier Rauolt, reported success with the antimalarial drug in a small study that was later debunked. It was sloppily done, and the doctor is an outlier and sort of crackpot within the French scientific community. He's popular with the far right for his climate science skepticism, controversial views on some vaccines, and conspiracy theories. I think he's their version of our Dr. Oz or Dr. Drew and some of the other crackpot scientists out there.

The treatment group and the control group were drawn from separate populations: the treatment group were all patients at the institution where the researchers worked, the Méditerranée Infection University Hospital Institute in Marseille, while the control patients came from other hospitals in the south of France. The treatment group (mean age 51.2) was significantly older than the control group (mean age 37.3), introducing another variable that could undermine the meaning of the results. The study was “open label”, meaning the physicians and patients knew which treatment they were receiving. The French researchers also treated some but not all of the treatment group patients with azithromycin, a common antibiotic, another complicating factor that was not randomized.

But even more important than these shortcomings in the design of the study is how the researchers chose to measure and report their results. Forty-two patients were initially included in the study. Three were transferred to the intensive care unit; one died, one left the hospital, aone stopped taking the treatment due to nausea. The other 36 eventually recovered, and those who received the drug cleared the virus from the system faster than those who did not.

If you had only heard about this study from the Fox News assertion of a “100% cure rate”, you might assume that the four patients with poor clinical outcomes (the three ICU visits and one death) had been unlucky enough to be in the group that did not receive the “cure”.

And yet, those four patients, as well as the patient with nausea and the one who left the hospital early, were all part of the treatment group. They were excluded from the topline results of the study because of the way that the researchers chose to measure and report the results: strictly based on the measurable presence of viruses in nasal swabs taken each day of the study. Since the patients were in the ICU or dead, their samples could not be taken and they were left out of the final analysis. Based on the nasal swabs of just the 36 patients who completed the study, those who received the drug cleared the virus from their systems faster than those who did not.

This is how an experiment in which 15% of the treatment group and 0% of the control had poor clinical outcomes could end up being reported as showing a “100% cure rate”.

I'm actually sad it failed. I think for some people on the left, there was a certain schadenfreude. It was kind of fun watching Trump get egg on his face for going all in on recommendations for an untested drug with serious side effects, especially when the studies came out showing it had no effect on outcomes and harmed more people than it helped. After all, it's fun to say, "I told you so."

Yeah, I get it. But the bigger problem is we still don't have any drug to treat this horrible virus. We still don't have a weapon against it in our arsenal yet.

A vaccine is at least a year or more away. We can't stay in lockdown for a year or more. I get that. But how can we come out when every day brings new and terrible information about what this virus does to the human body - the latest being that it somehow causes blood clots. Some of the people who have died have not succumbed to Acute Respiratory Distress Syndrome (ARDS) but actually to blood clots in their lungs and elsewhere. A Broadway actor, Nick Cordero, had his leg amputated. The more we learn about this novel coronavirus the less good news there is.

Yet, there are states determined to open up prematurely, while their rates of new infection are still climbing, like Georgia, Texas, Florida, and Tennessee. And other places where governors are bravely following scientific advice even in the face of organized demonstrations by the far right and tea party groups.

So, what is the answer?

I don't think we can keep things closed indefinitely. Right now, despite the efforts of the far right fringe, most people are more afraid of their state opening too soon than they are of it staying closed, despite their own economic hardship. At least three polls, Gallup, Pew, and Washington Post have found that more people are pessimistic about things getting better and fear their state reopening too soon. And most disapprove of the way Donald Trump is handling this often for that reason.

Even though nobody wants to be unemployed and people are very worried about how they are going to pay their bills, they understandably are also scared of getting a truly frightening disease that kills and leaves people with damaged organs. They don't want to get this themselves and they don't want their loved ones to get it. Hell, most people are disinfecting and wiping down groceries, taking showers and leaving clothes in the garage every time they go out to the grocery store. Do you think they want to go sit in an office all day with a bunch of coworkers, go to a restaurant, a theater, or gym?

So we have to find a solution that gives us some safety to begin a gradual return to normality. I already talked about the CDC guidelines yesterday. It includes a 14 day period with declining death rates, no new cases, and things slowly reopening in stages. It would be contingent on widespread testing and contact tracing. All that would help in controlling fresh outbreaks, protecting large groups of people But what about those unlucky ones who still contract the disease?

We can't guarantee one hundred percent safety. Let's acknowledge that. Even before this new virus, people got sick. They got serious illnesses and some didn't survive. If this ugly virus never showed up, we would not be one hundred percent safe from disease and death. But we always had tools to fight disease, methods to mitigate the risk, not just to the entire group, but to the individual who still got ill. We had antibiotics for bacterial diseases, chemotherapy for cancers, statins for heart disease, and other drugs and methods for treating illnesses so that more people survived.

Hopefully, we will eventually find a vaccine and this disease will be eliminated, like polio, smallpox, and other diseases before it. Until then, we need stepped up research on antivirals. There's actually a list of different approaches being researched, with antivirals like remdesivir, a drug originally tried for Ebola; EIDD 28; favipiravir, a Japanese antiviral; and several imunosuppressive drugs to control the cytokine storm the virus often causes, where the body's own immune system attack itself.

This older article, which was written before chloroquine flamed out, shows some of the approaches researchers are taking. Other than the chloroquine, studies of the other approaches remain ongoing, along with the search for a vaccine.

So, ultimately, I think we will have a drug treatment as a bridge until we find a vaccine. But even with a drug - or hopefully more than one - the key is still going to be testing. I suspect that just like with other illnesses, the earlier you catch it and treat it, the better the success rate. This is probably true of any virus, where getting an effective drug into a patient while the viral load is still relatively low, will yield the most success.

This desperate search for the cure is an international effort with scientists, labs, and drug companies sharing information to find something. Still, safety cannot be compromised. Before anything comes to market to fight this disease, it has to prove safe. Chloroquine did not meet that standard here, despite a long history of use for malaria and autoimmune diseases like lupus. But in covid-19 sufferers in seemed to increase heart problems and they did worse than those not on the treatment.

Remdesivir was already tested for Ebola and cleared basic safety trials. Unfortunately, it was not effective for Ebola. It also has the drawback of being an intravenous drug, which means it has to be taken in the hospital, or a patient would have to have a port put into their arm or chest to administer it. EIDD is an oral medication, which make it easier to use and more likely to be given for even mild to moderate cases. Both these medications, and any others have to prove both safe and effective specifically for covid-19, And that will take a while. But we are not starting from scratch with any of these. They've already been tested, and in some cases already used, for other diseases. So testing on patients could yield results in a few months, rather than a few years.

None of this is without risks. And none of them might work. But they are currently our best hope until a vaccine comes along.