If you’re waiting for a widely-available Covid-19 vaccine to leave your house, you’re going to have to wait a couple of years. But if you have hope of life returning somewhat to normal any time before 2022, then you are rooting for clinical treatments for the disease — something that helps people who get sick with Covid-19 get well. Fortunately, there are many promising drugs, and scientific trials being conducted all over the world. Positive results could come within a matter of months. As I spent the past several days researching this topic, I felt myself growing more optimistic than I have in weeks. So I hope you do, too. If I were you, I’d spend a lot of time following news on “therapeutic” drugs right now.
Unfortunately, the race for a cure is in danger of being politicized. You’re insane if you are doing anything other than rooting for every one of these treatments to work, and you’re also insane if you are doing anything to get in the way of the hard science that needs to be done to make sure a) these treatments really do stop Covid-19 and b) they don’t do more harm than Covid-19 along the way.
I spent a bit of time recently reading the dark side of the Internet, on which experimental treatments for Covid-19, Remdesivir and Hydroxychloroquine, have been dragged into absurd Red vs. Blue / Liberal vs Conservative / Republican vs. Democrat camps. This hurts my heart and my brain, so I’ve done the only thing I know how to do, a lot of research. There are a lot of interesting parallels between cybersecurity, which I know a fair bit about, and virology, which I don’t. I share what I found below. There’s some running with scissors involved here, and some imprecise metaphors, but my main goal is to point you to other places for further reading — and give you an appreciation for the amazing science that is happening around the world in a desperate attempt to save your life, my life, and our way of life.
To get to the bottom line quickly, this Ars Technica story is the best civilian-readable summary of drugs being tested. And the best scientific summary of treatments available I found was published this week by the Journal of American Medicine, JAMA.
I started down this road last week when I read about a virologist who got involved in his field because he had a sort of scientific, professional respect for the devious ways virus attack humans — it sounded to me like the same kind of adversarial respect that cybersecurity professionals have for computer criminals. He admired Covid-19’s ability to infect hosts while hiding its arrival for several days — symptoms might take a week to develop — leading to asymptomatic transmission. That’s probably the most dangerous aspect of this Coronavirus, as it makes “stay at home if you feel sick” advice worthless. Covid-19 covers its tracks when it infects people. Coronavirus has added a bit of social engineering to its hacker bag of tricks.
Fortunately, we have pretty good hackers on our side, too. The trick to stopping a virus is finding vulnerabilities in it, much as hackers look for accidental flaws in software than can be exploited. A massive, worldwide bug-hunting contest is underway right now. If you want another metaphor, think of how the Rebel Alliance defeated the Galactic Empire in the original Star Wars film — by sneaking a perfect shot inside the Death Star’s thermal exhaust port, the only vulnerable spot on the surface of that monster machine.
Scientists are looking for a similar tiny opening in Covid; fortunately, the virus appears to have more than one potential vulnerability. Some treatments try to make the hosts (people) uninhabitable for Covid, in one case by changing pH levels; others are tricking the “software” Covid uses to replicate itself; still others are stopping the body’s often deadly immune system over-reaction to Covid (the “Cytokine storm”).
Each approach works very differently. Some treatments will prove better when administered early on. Some will need to be timed later, when the disease has progressed to dire phases. Inhibiting the body’s immune system is a good idea when it’s over-reacting, but a bad idea at the onset of a disease.
To understand why extensive testing must be done, and why that takes time, it’s important for civilians to have some notion of just how risky any of these treatments can be. One treatment essentially reprograms RNA to disable to virus. That works well, unless it also reprograms “good” RNA in the body along the way. This isn’t quite rearranging atoms inside your body, but it’s close. It’s also close to playing God. So it must be done with great care.
Also, humans are a diverse bunch, so figuring out how much of a drug to administer — the dosage — to people of all ages and medical conditions can be as tricky as inventing the cure itself. That’s why drugs, and dosages, take months and months to complete.
Finally, it’s important to understand that a single story of a person taking a drug and recovering from Covid doesn’t mean much. The cure could be a coincidence. And if that’s true, giving a drug to someone that doesn’t actually help them could prevent them from getting a treatment that really does help. That’s why public guessing about cures is a dangerous game to play.
The only way to really know something works is through randomized controlled trials, which involve carefully selected test subjects, patients “treated” with placebos, double-blind design, and so on. You’re not hearing much about these kinds of trials now because doctors who are desperate to help very sick people are administering drugs under “compassionate use” exemptions — just trying to save lives — so many are not participating in randomized controlled trials. There are obvious risks to treating a direly ill population with placebos, of course.
Notice, I haven’t mentioned any drug names yet. That’s because I’m trying to keep politics (?) out of this. I figure if you’ve read this far, you’re interested in genuine information. So here’s where to find out more about the various drugs being tried. As you read the list, remember, it’s quite likely that there will be no silver bullet treatment, but rather several of these treatments will help, or a combination of them will.
The most promising, and most immediately available, drugs already exist and were prepared to treat other viruses. A fantastic, if overwhelming, chart of all current potential drug therapies and their drawbacks is available from JAMA. A free account is necessary.
There was a lot of noise about Remdesivir at the end of this week because premature results of a small study in Chicago on moderately-sick Covid patients offered promising results, according to a news report at StatNews.com. That sent the stock market into a tizzy. Everyone involved in the study says it’s premature to draw any conclusions from it. But even before that story was published, JAMA had described Remdesivir as “the most promising therapy.”
Remdesivir has the potential to stop Covid-19 from reproducing. Covid-19 breaks into human cells and uses RNA to make copies of itself. Remdesivir screws with the copy machine, so the duplicates end up with the wrong “software,” and are no longer dangerous. This technique has the virtue of targeting a whole family of viruses — it worked against MERS and SARS — while at the same time, it can be designed to find and attack only RNA that is specific to viruses. It was designed to treat Ebola, but it’s clinical trial results were disappointing. So will Remdesivir’s early positive results hold up to rigorous testing? We don’t know. But one of the first randomized controlled trials could offer results as early as May, so we might know more soon. At the moment,
Remdesivir requires intravenous treatment, which means a hospital stay, so it’s more expensive than other drugs, and it would be difficult to scale during a large outbreak.
Remdesivir actually inhibits a specific type of RNA called RNA polymerase. Over at the online Protein Database, RNA polymerase was “protein of the month.” Learn more about how Remdesivir impacts at the Journal of Biological Chemistry and at ScienceDaily.com
Covid-19 needs to break into human cells to acquire the parts it needs to reproduce. Like most metaphors, “breaking in” is a bad one, as it doesn’t exactly break down the door of a cell membrane. Instead, it attaches to the outside of respiratory cells and works its way inside the cell through a more elaborate process that requires, in part, a cellular reaction that lowers pH levels, a process called glycosylation. Chloroquine and hydroxychloroquine, designed for malaria prevention, seem to inhibit this change in pH, which makes the cell uninhabitable for Covid. For a better understanding of glycosylation and how chloroquine inhibits host-cell entry, including discussion of the signature “spike” protein from which coronavirus gets its name, read this piece at Genetic Engineering and Biotechnology News.
Hydroxychloroquine has several advantages; the main one is it’s been around for a long time, and it’s more widely available than other treatments. It could, theoretically, be administered at home after a video visit. But doctors are worried about side effects, particularly heart disease, such as arrhythmia. It’s also possible to overdose on Hydroxychloroquine. Patients being treated with the drug are often hooked up to constant heart monitoring. There are worries about long-term term heart problems associated with use of the drug. Still, it’s widespread use and long track record are hopeful signs that incidence of side effects could be minimal.
Lopinavir/Ritonavir — These HIV drugs are protease inhibitors, which work by preventing virus proteins from subdividing and replicating. The drugs were initially used in China during the earliest stages of Coronavirus, with anecdotal reports of success. But a subsequent study published by the New England Journal of Medicine found the drugs had no positive effect on patients. It’s possible that these drugs will be more effective if administered early on in the course of a Covid infection, JAMA says.
Tocilizumab — Some Covid-19 patients are dying because their body’s immune system rises up to fight the virus and whirls itself into overdrive, which is often fatal — a condition called at cytokine storm. The drug Tocilizumab blocks a protein known as IL-6 that’s associated with inflammation and is involved in the cytokine reaction. Tocilizumab has been used with anecdotal success in Covid-19 patients and trials are underway; the drug can have serious side effects, according to its manufacturer. Read more at ScienceDirect.com
If you’re looking for information on lesser-known drug treatments, I’d highly suggest reading that JAMA article.
But as you do, ponder the frustration expressed by Vincent Racaniello, a faculty member at Columbia University and the host of the This Week in Virology podcast. Plenty of drugs were created in reaction to SARS and MERS, he said, but because those potential epidemics petered our, research on the drugs was never completed. It’s quite likely that something scientists invented back then would have been a ready-made effective treatment for Covid-19 — governments and corporations around the world didn’t want to spend the money, however.
“To Racaniello, our response to SARS and MERS wasted a great opportunity,” Ars Technica wrote.
“We could have had a broadly acting antiviral that targeted RNA polymerase by now,” he told Ars. “We could have had people isolating the gene from various bat coronaviruses and doing screens to see if we could find compounds that could have inhibited them all. That’s the kind of thing that’s doable and should have been done. And if we had such antivirals ready, they could have been used right at the onset in China.”