As the coronavirus pandemic has become a mainstay of our lives, everyone is awaiting an effective treatment or a vaccine for Covid-19 that will allow our country to begin normalising.
There’s been near-constant speculation about which potential drugs could be effective against the virus, but early tactics for treatment were mostly based on scientists’ best guesses. The amount of “fear and emotion and psychological angst” in this pandemic produced a lot of discussion on specific drugs before clinical trials got underway, said Dr. Dan Culver, a pulmonologist at Cleveland Clinic leading the clinical trials committee evaluating Covid-19 research.
“Some of the press got ahead of the science, let me put it that way,” he said. “I think we’re seeing a little bit of a drawback on that now; people are realising this is a marathon and not a sprint. Some of the things that are happening now are being done with a little more rigour and circumspection.”
Which drugs will become effective Covid-19 treatments still remains to be seen, but there are a few names you’ve likely heard tossed around in the news ― from hydroxychloroquine to remdesivir ― and several more worth knowing more about.
Here, experts give a breakdown on what we know, and what we don’t, about coronavirus treatments so far.
Initially, some experts were hopeful about hydroxychloroquine as a treatment of Covid-19. The medicine, which is an antimalarial drug with anti-inflammatory properties, is also used in patients who have diseases like rheumatoid arthritis and lupus.
“It’s a drug that has some activity in the lab against coronaviruses, and a drug that has a very long history of safety and efficacy for connective tissue diseases,” said Dr. Michael Dubé, a professor of medicine and interim chief of infectious disease at the University of Southern California’s Keck School of Medicine. “Because of its availability, it was very early on proposed as a treatment for Covid-19.”
However, so far there’s “very little evidence of efficacy and accumulating evidence for toxicity,” Dubé said. The push for it to be a treatment for Covid-19 from President Donald Trump has also led to a shortage for people who need it and other dangerous consequences.
In mid-May, a study published in The Lancet suggested that patients receiving hydroxychloroquine were dying at higher rates and experiencing more heart problems than those receiving other treatments. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a leader of the White House’s coronavirus task force, told CNN, “The scientific data is really quite evident now about the lack of efficacy for it.”
The Lancet study and the drug is still being debated by researchers, though. Part of the problem is that hydroxychloroquine has not seen data from a randomised, placebo-controlled clinical trial, Dubé said. “But the signal is that at least in sick, hospitalised patients, there may be increased risk of cardiac problems” like arrhythmias, he explained.
Remdesivir is an antiviral drug developed by Gilead to treat Covid-19 when a person is already sick. Dubé said the treatment has “fairly broad antiviral activity, and was thought to possibly be useful for Ebola, for example, and again, studies in the lab suggested that remdesivir had activity against coronavirus.”
Remdesivir was brought rapidly to clinical trials, where “one of the two placebo-controlled remdesivir trials showed a benefit” over placebo, Dubé added.
In the clinical trial, patients receiving remdesivir recovered slightly faster than those who didn’t; the mortality rate of patients on the drug was also slightly lower, but not statistically significant.
Even so, the trial was stopped early and the drug was sent out to Covid-19 patients. “There’s been a larger disbursement of all of Gilead’s supply of remdesivir to the states for distribution,” Culver said.
The drug is administered through an IV, and seems fairly well-tolerated by patients thus far. “I think that remdesivir is probably somewhat helpful, but it’s more of a single [hit], not a home run,” Culver said. “It’s probably going to mitigate the impact of the virus, but I don’t think this will be anything like a cure.”
Plasma Or Antibody Treatment
Those who have been previously exposed to or sick from the coronavirus will have experienced an immune response against it, developing antibodies that can possibly protect them further against the disease.
The idea for treatment is that these antibodies people have developed can then be “passively infused into patients who are infected” with Covid-19 through the form of convalescent plasma (aka the liquid part of the blood) to “augment or bolster” their own immune response against the virus, Culver said.
“This is an idea that’s been around since the Spanish flu pandemic over 100 years ago,” Culver added.
The antibodies will “hopefully neutralise the virus and stop it from spreading and replicating,” according to Dubé. “It probably has its greatest chance of being a preventative therapy by blocking the virus before it has a chance to establish a foothold.”
One drawback? “There can be antibodies present that can actually make the disease worse, a phenomenon known as ‘antibody dependent enhancement,’” Dubé said. “But hopefully the plasma currently being used will have antibodies that will neutralise the virus without having the potential to enhance the viral infection.”
It’s still tough to say how effective convalescent plasma is, as most studies thus far have given inconclusive results, Culver said.
“We also don’t know how to screen for antibodies yet,” he said. “In a potential donor, will that donor be an effective donor who can really grant immunity to a recipient of plasma? Or will the donor be less effective? We don’t really know.”
Most patients in the United States are receiving this therapy as part of an expanded access program out of Mayo Clinic.
“The drug is well-tolerated, and the incidence of side effects is low, though we don’t know how useful it will be,” Culver noted. That said, he still “would encourage people who have previously had Covid-19 to contact their local blood bank” about the potential to donate plasma.
There have been reports of high-dose, IV-administered vitamin C for hospital patients sick with Covid-19.
“Certainly, there’s some data that it augments immune function and lots of data that it has strong antioxidant properties,” Culver said. “This has, of course, been proposed as a treatment for infections and a variety of inflammatory conditions. In many cases, it failed or had marginal benefits. But I certainly think there may be some possibility that it can be helpful.”
Culver said the vitamin C could “reduce or dampen the virus rather than curing it — but maybe for many patients, that’s enough,” he said. “At Cleveland Clinic, we are doing a trial of vitamin C, zinc, and a combination of the two, in patients who have Covid but are not administered to the hospital. Zinc, even, has a little bit better data, especially in influenza.”
Culver said he would not encourage people to go out and take vitamin C or zinc to prevent covid-19, however. “The doses that you need for this are quite high” and must be administered in the hospital, he said.
“The Moderna vaccine showed in a very small number of patients that antibodies can be generated after administering the vaccines,” he said. “The recipients’ immune systems did generate antibodies against the spike protein, which is the goal of the vaccine. But it’s a long way off from proving the vaccine works in a broad population, and it’s also a long way off from proving the antibodies actually protect the patients from infection.”
The next steps, for Moderna, and all vaccine candidates, will be showing that the vaccination creates antibodies in a broad spectrum of people, “including elderly patients — who are not well-studied in these, but are at the highest risk — and then proving that that actually protects people from infection,” Culver said.
“This will require longer and larger trials, with many more patients, and the readout of those trials I don’t expect to happen anytime this year. If we are extremely lucky, it’ll be the first half of 2021,” he added.
To speed up innovation, researchers are throwing a host of new vaccine technologies at Covid-19.
For example, using parts of the spike protein of the virus (those “spikes” you see on renderings of Covid-19), Culver said. Some scientists are working on vaccines where they hide parts of the virus in another, non-infectious virus ― called an adenovirus ― which is used as a “Trojan horse,” Culver said. The spike protein may be the only piece of COVID-19 that is introduced into a person’s system through the adenovirus, and that can prompt an immune system response against it.
Oxford University’s Jenner Institute ― which has been in the news with frequency similar to Moderna ― is working on a vaccine using an “adenovirus construct,” Culver said. The other two broad categories for vaccines involve DNA and RNA ― so, the virus itself is not introduced into the body, but rather genetic material from the virus is introduced instead.
Other Treatment Ideas
These are far from the only treatments under consideration for Covid-19. Dubé said another drug called Kaletra could have some promise, given results from a study published in the New England Journal of Medicine.
“Kaletra is an HIV drug that has been around for well over a decade and appears to have activity against coronavirus in the lab,” he said. “The Kaletra study was widely reported as being negative, and it wasn’t negative at all. There was actually more clinical improvement with the Kaletra, and a shortened ICU stay by four to five days with the use of the drug.”
Dubé, who was not affiliated with the study, added that the drug is readily available and able to be administered orally instead of through an IV.
Other treatments are less about targeting the virus, and more about controlling the overwhelming immune response in some severely ill Covid-19 patients ― often referred to as a cytokine storm.
“You can sort of combine the strategy of controlling the virus with the antiviral, as well as trying to control the inflammatory response with an anti-inflammatory intervention,” Dubé said. “The most mature data at this time is with tocilizumab. This is a very promising anti-inflammatory drug that can shut off the excessive inflammation that occurs in some people with severe Covid that really drives the ARDS and need for ventilators.” (ARDS is a respiratory complication that can happen when someone gets really sick from Covid-19.)
Dubé’s team at USC is also looking into the effects of the drug baricitinib against Covid-19, which may work in a similar fashion to curb the immune system effects.
Dubé does not believe there will ever be one miracle cure for Covid-19. “It’s unlikely we are going to find a single antiviral intervention that will be sufficient to prevent the need for a ventilator or prevent people from dying,” he said. “It’s really going to be a combination of drugs that act against the virus and clamp down the immune system that is likely to make the most impact in seriously ill individuals.”
CORRECTION: A previous version of this article listed Dubé as the interim chief of infectious disease at the University of California.