Has A Corner Finally Been Turned On Covid Treatment?

Between breakthrough infections due to declining vaccine efficacy over time, as well as the number of people who either havent been vaccinated - or refuse to be - there are still a significant number of hosts in whom the virus may find a home from which to propagate. 

The growing number of medications in pill form that reduce Covid's lethalilty, as well as the probability that victims end up in the hospital means that the disease's risk is reduced to a level where it can be managed more effectively. JL

Kelsey Piper reports in Vox:

Researchers have made some advances in figuring out how to treat Covid-19 once you’ve contracted it. Of particular promise are medications available in a form that should be especially useful in the fight against the virus: pills. By developing better at-home therapies, we can beat the disease back among both vaccinated people with breakthrough infections and individuals who have declined to be vaccinated.

When the vaccines against Covid-19 first started rolling out less than a year ago, there was widespread hope that it signaled the beginning of the end of the pandemic. As we head into another winter, however, things are much more uncertain than many people had hoped: As much as we might want to put the pandemic behind us, the delta surge and vaccine hesitancy have ensured that Covid-19 has lingered.

But there’s another new development on the horizon that, in combination with vaccines, might really be a game changer.

In recent months, researchers have made some advances in figuring out how to treat Covid-19 once you’ve contracted it. Of particular promise are medications available in a form that should be especially useful in the fight against the virus: pills. Pills are easy to store and ship, making them a more feasible option for worldwide distribution, and they don’t tax already overloaded hospital resources during a surge.

To understand why the development of anti-Covid pills is a big deal, think about how we’ve been able to treat Covid-19 thus far. In the nearly two years since this coronavirus started spreading, we’ve learned a lot about how to care for patients who are sick enough to require hospital care. Cheap, widely available drugs such as dexamethasone have substantially reduced the hospital mortality rate for severe Covid-19.

But there are fewer options for sick people who haven’t been hospitalized. The one outpatient treatment authorized for emergency use and widely available in the US is monoclonal antibodies, which work quite well but must be administered as either a single IV infusion or a series of four shots in a medical setting.

Uptake of monoclonal antibodies reportedly isn’t as high as it should be, and the treatment itself, while free to US patients, is pricey, costing the US government $2,100 per dose.

So as effective as monoclonal antibodies have been, there’s still a large void in our early treatment arsenal. When the virus surges in an area, hospitals get overwhelmed, meaning that people who end up needing treatment might not get it. Meanwhile, people with mild to moderate cases are told to stay home, where they have very few options.

The lack of good early treatments for Covid-19 has led to high demand for drugs that have gained adherents but probably don’t help all that much, from hydroxychloroquine to metformin to ivermectin. The effort to figure out how and whether those treatments work has been marred by widespread fraud in published research investigating them.

But there’s finally been some real progress on identifying Covid-19 treatments that not only are highly effective but also available for Covid-19 sufferers to take at home.

Fighting Covid-19 with a pill

One pill that’s been shown to be effective against the disease wasn’t even made to fight Covid-19.

Fluvoxamine is a cheap, generic antidepressant that’s been around since the 1990s. It also appears to reduce hospitalizations and deaths by Covid-19 by up to 30 percent, according to the results of a randomized, controlled trial, the initial findings of which I reported on back in August. Results from the so-called TOGETHER study, which tested fluvoxamine and some other treatments, were recently published in The Lancet medical journal.

How does fluvoxamine work in the case of Covid-19? Researchers’ best guess is that it modulates the body’s inflammatory response and reduces lung damage as the immune system fights off the coronavirus.

A 30 percent reduction in hospitalizations and deaths may not strike you as particularly high, but the drug is cheap (only $4 per dose) and has a demonstrated track record of safety (it’s FDA approved), which should strengthen the case for adding it to the global arsenal in the fight against the pandemic.

Despite encouraging trial results and a great safety profile, the National Institutes of Health’s treatment guidelines for fluvoxamine haven’t been updated since April, and the drug isn’t widely prescribed or recommended for Covid-19 patients. Doctors can make the call to prescribe fluvoxamine as an off-label treatment, but many might be reluctant to do so until the drug’s official guidelines incorporate evidence from large, reputable clinical studies demonstrating its efficacy. Now that the TOGETHER results have been published, though, doctors might be more willing to write those prescriptions.

An even more promising pill is Merck’s molnupiravir. Unlike fluvoxamine, it’s not already FDA approved, but it’s also repurposed after a fashion: Merck began developing the antiviral as an influenza treatment. It’s taken as a batch of up to four pills, twice a day for five days.

In Merck’s studies, molnupiravir reduced Covid-19 hospitalizations and deaths by about half. The UK granted the drug “conditional authorization” last week; the FDA has been reviewing the data since mid-October and will hold a hearing to discuss the data on November 30.

The US government has committed to purchasing 1.7 million courses of the drug for about $700 apiece once it’s approved or authorized for emergency use. Merck has licensed the generic manufacturing of molnupiravir at a much, much cheaper price in more than 100 developing countries, and the success of that program will be key for molnupiravir to make a difference worldwide.

Finally, Pfizer’s Paxlovid is a little farther away from widespread availability, but recent research suggests it might be poised to make a huge difference. Paxlovid is an antiviral developed to target Covid-19 specifically by blocking a specific enzyme the virus needs to reproduce itself.

An interim analysis of an ongoing trial published by Pfizer last week noted that Paxlovid reduced the risk of hospitalization or death by 89 percent for adults at risk of severe Covid-19. That’s a huge effect size, and it’s always wise to be a little skeptical of results that good.

But if the studies hold up — and there are more ongoing that could support or refute the existing data — that could effectively mean the end of the pandemic. For many people, getting sick from Covid-19 would be much less of a danger.

Down the pike

There are many other early Covid-19 treatments under development and in testing, too. For instance, researchers in the UK found that inhaled budesonide, a medication used to treat asthma, reduced recovery time, hospital admissions, and deaths in Covid-19 patients; studies are underway to confirm those results and to check how budesonide interacts with other early treatments.

The antiviral remdesivir offers little benefit for Covid-19 patients and probably “makes little or no difference” in mortality, according to a systematic review of multiple studies on its effects. Gilead Sciences is developing a pill version for non-hospitalized patients in the hope that remdesivir might work better as an early treatment; some early evidence bears that out.

The FDA database of clinical trials for Covid-19 lists hundreds of studies on potential treatments, from repurposed medications to newly developed medicines to combination protocols of other promising drugs. The vast majority of those won’t pan out, but it only takes a few.

I suspect I’m not alone in being desperate for a return to normal — to concerts and indoor events, to in-person playdates for kids, for frictionless travel — while still being conscious of the fact that more than a thousand people are still dying of Covid-19 in the US every day.

The virus might be approaching endemicity, but those death counts needn’t become a new normal. By developing better at-home therapies, we can beat the disease back among both vaccinated people with breakthrough infections and individuals who have declined to be vaccinated. There’s some really good news here, and we owe a debt to the scientists who’ve worked to develop, test, and understand these drugs.