A researcher's gloved hands sort blood samples in test tubes
A lab technician sorts blood samples for a COVID-19 study.

Researchers have been working furiously to identify medications and treatments to combat the novel coronavirus that causes COVID-19. 

While there are still no definitive answers, the Food and Drug Administration recently authorized emergency use of what’s called convalescent blood plasma, an antibody-rich fluid that’s donated by people who have survived a previous COVID-19 infection. This emergency use authorization (EUA) will make it easier for doctors to give donated plasma to COVID-19 patients as part of a standard course of hospital treatment.

But some experts—including, according to The New York Times, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID)—recently said that more evidence was still needed on whether plasma is a safe and effective treatment and that the data from the study used to justify the authorization was not strong enough.

“While the data to date show some positive signals that convalescent plasma can be helpful in treating individuals with COVID-19, especially if given early in the trajectory of disease, we lack the randomized controlled trial data we need to better understand its utility in COVID-19 treatment,” Thomas File, the president of the Infectious Diseases Society of America (IDSA), said in a statement. 

This was not the first time the rapidly evolving information on COVID-19 has led to confusion and conflicting advice.

In March, for example, the FDA authorized emergency use of the anti-malarial medications hydroxychloroquine and chloroquine, “perhaps out of desperation,” says Paul Goepfert, professor of medicine and microbiology and director of the Alabama Vaccine Research Clinic at the University of Alabama at Birmingham. Three months later, as research increasingly pointed toward “known harms and no available evidence of benefits,” according to the American College of Physicians, that EUA was revoked. 

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Researchers around the world are continuing to explore a number of other possible treatments, ranging from dexamethasone (an inexpensive, widely available steroid) to remdesivir (an expensive, experimental antiviral). The IDSA released guidelines outlining which therapies are worth testing as potential treatments for this new disease that many doctors are still trying to understand. 

“We’re learning a lot quickly—more so than we have with any other virus,” Goepfert says.

But it will take more rigorous studies before scientists truly understand what will work best. Drugs that initially show promise may turn out to be dangerous or ineffective. Hundreds of trials are still underway, involving thousands of patients in the U.S. and around the world. 

Here’s a rundown on what we know so far about treating COVID-19. 

The Basics of Hospital Care

Most people who contract COVID-19 can be treated at home and start to feel better after a week or so, but about one-fifth of patients experience worsening symptoms, such as difficulty breathing, according to the Centers for Disease Control and Prevention. It’s people with these more severe cases who may need to be treated in the hospital.

Care in the hospital is aimed at supporting patients as their body fights off the virus, Goepfert says. That entails supplemental oxygen to help people breathe, intravenous fluids if they are dehydrated, and antibiotics to treat secondary bacterial infections, such as pneumonia. If patients receiving oxygen still aren’t able to get enough of it into their bloodstream, doctors may put them on a ventilator to help them breathe while their body fights the infection. 

Blood Plasma From Recovered Patients

This experimental therapy, called convalescent plasma, collects blood plasma from people who have recovered from COVID-19 and injects it into people fighting the disease. The idea is that the blood of survivors, which contains antibodies against the virus, may help recipients who are ill recover faster or may prevent the disease in those at high risk, such as frontline medical workers and those living with a COVID-19 patient.

Dating back to the late 19th century, the venerable treatment is a “great idea,” says Gregory Poland, an infectious disease expert and director of the Mayo Clinic’s Vaccine Research Group in Rochester, Minn. “It has worked in many other infections, and therefore, there is reason to suspect it may be helpful.”

Early data from research in China was promising. A national initiative to investigate the therapy is still seeking plasma donors in the U.S. (Read more about how to help.) And in April, the FDA expanded the use of convalescent plasma to make it available to some patients with severe disease outside of clinical trials.

Then, in August, the agency authorized convalescent plasma for emergency use. Some researchers, including Frank Harrell, a professor of biostatistics at Vanderbilt University School of Medicine in Nashville, Tenn., have expressed concern that the benefits of plasma were overstated when the EUA was announced. The authorization was largely based on data collected from 35,322 patients who received plasma through the FDA’s expanded access program.

study from the Mayo Clinic analyzing that data, which has not yet been peer-reviewed, indicated that patients who received plasma with high levels of antibodies were more likely to survive than patients who received plasma with low levels of antibodies. The study also found that patients who received plasma within the first three days after being diagnosed fared better than patients who received plasma on or after day four after diagnosis.

The body of evidence seems to indicate that plasma is safe, but it is not yet sufficient to say that we know that plasma works, says Shmuel Shoham, an associate professor of medicine and associate director of the Transplant and Oncology Infectious Diseases Center at the Johns Hopkins University School of Medicine in Baltimore.

“What we don’t have are the randomized controlled trials, which are the gold standard to bring it home,” he says. Such trials involve a control group that does not receive the plasma treatment, something the Mayo Clinic study did not include. (Shoham, who is a fellow of the IDSA, is involved with two randomized control trials of plasma that are still trying to recruit patients.)

Even if additional data suggests that convalescent plasma is effective, it still is not a cure or even a scalable treatment—it’s just a stopgap measure, Poland says. The immunity conferred generally lasts only a few weeks. And because plasma from one patient treats only two or three others, it’s not practical for widespread use. “As a crowdsourced product there could be problems with supply,” Shoham says.

The National Institutes of Health is coordinating studies looking at how a more scalable treatment might be manufactured from plasma, but the availability of such a product would still be a long way off.

Other Experimental Drugs

Beyond supportive care such as oxygen, researchers are studying several therapies other than convalescent plasma that could ease symptoms and possibly ward off life-threatening complications. “We do not currently have any known treatment that will kill the virus or decrease its growth,” Goepfert says.

And with doctors sometimes trying multiple drugs in seriously ill patients, when people recover it’s hard to know what—if anything—helped. Or whether a drug caused harm. That’s why clinical trials are so important, Goepfert says.

Here are some of the therapies researchers are currently investigating. 

Chloroquine and Hydroxychloroquine
Research shows that, in test tubes, these anti-malarial drugs can block coronaviruses such as the one that causes COVID-19 from invading cells. Scientists at first theorized that the anti-inflammatory effect of the drugs, which makes them useful against arthritis, could reduce the swelling in the lungs that can make it hard for people with COVID-19 to breathe.

Early evidence from experiments in humans with the virus were mixed. Ultimately, larger trials suggested that the potential harms may outweigh any potential benefits. “This drug may not be effective to treat COVID-19,” the FDA concluded in the June 15 letter (PDF) revoking its emergency use authorization.  

What’s important to remember, Goepfert says, is that “none of these drugs is innocuous.” Hydroxychloroquine and azithromycin can trigger dangerous irregular heart rhythms, and the drugs may be more dangerous when given together.

IL-6 Inhibitors
Clinical trials are underway to study whether drugs such as sarilumab (Kevzara) and tocilizumab (Actemra), used to treat autoimmune disorders such as rheumatoid arthritis, could help prevent severe complications of COVID-19. Because the drugs help prevent the immune system from attacking healthy cells, researchers theorize that they may help quell the overactive immune response in COVID-19 patients (known as a cytokine storm) that leads to dangerous inflammation and damage to the lungs. But because of uncertainty about its efficacy and potentially harmful side effects, the IDSA says that tocilizumab should be used only as part of a clinical trial.

Lopinavir/Ritonavir (Kaletra)
Studies in test tubes and animals suggest that this HIV drug may work against other types of coronaviruses. But in a recent trial of 199 people with severe COVID-19 infections, those who took Kaletra fared no better than those who didn’t. Researchers hope the drug will work better if given earlier in the course of the illness. The IDSA advises that this combination should also be used only in the context of a clinical trial.

Remdesivir
Remdesivir, originally developed by drugmaker Gilead Sciences to combat Ebola, is not on the market in the U.S. or elsewhere, though it is being used in some studies.

The intravenous antiviral first appeared to help reduce the severity of COVID-19 in a study, sponsored by Gilead, of 53 hospitalized patients. But the study was small and did not directly compare those who got the drug with those who didn’t.

Results from an NIAID trial of 1,063 patients, published May 22 in the New England Journal of Medicine, found that those hospitalized with COVID-19 who received remdesivir recovered enough to be discharged or resume normal activities in 11 days, vs. 15 days in those who received a placebo.

Fauci, discussing the results April 29, said the mortality rate in the study, at 8 percent for those taking remdesivir compared with 11 percent for people on a placebo, “trended toward being better” but wasn’t statistically important. “The data need to be further analyzed,” he said.

A study published in The Lancet the same day the NIAID results were announced had different findings. It found that of 237 patients with serious COVID-19, those given remdesivir did not recover faster or clear the virus more quickly than those given a placebo. The researchers wrote that they expected other, ongoing trials of remdesivir to “confirm or refute” their findings.

Gilead is also sponsoring research to see whether a shorter course of remdesivir—five days instead of 10—has an effect.

In addition, studies using remdesivir are underway in people with milder symptoms. Like the antiviral drugs used against the flu (such as Tamiflu), remdesivir may work better if given soon after patients first develop symptoms, Goepfert says.

Steroids
Doctors were cautious about using steroids early in the pandemic, according to the IDSA, because they can suppress an immune response and make it more difficult to fight off an infection. But as it became clear that many of the most dangerous symptoms of COVID-19 emerged because of an overactive immune response—known as a cytokine storm—research began to suggest that an inexpensive steroid called dexamethasone might help in certain severe cases. 

A clinical trial involving thousands of patients, published July 17 in the New England Journal of Medicine, found that a 10-day course of dexamethasone significantly reduced deaths in patients on ventilators or on oxygen. There was no evidence of any benefit in patients who were not ventilated or on oxygen, and the study did not look at patients who were not hospitalized.

Based largely on that trial, the IDSA guidelines recommend steroids such as dexamethasone for hospitalized patients with severe COVID-19 but cautions against their use in patients who do not require supplemental oxygen, warning that they may cause harm.

“Compared to other drugs that we have seen data for thus far, [dexamethasone] is the one that seems to have the greatest effect on patients, especially those who are critically ill,” says Krutika Kuppalli, an infectious diseases physician in the Bay Area and vice chair of the IDSA Global Health Committee. Still, she adds, doctors need more data to better understand potential side effects and long-term outcomes, especially because previous experiments using other steroids to treat COVID-19 have had variable results.

The Real Hope: A Vaccine

The most promising path for returning to prepandemic life is to immunize people to protect them against the virus that causes COVID-19. And researchers have made unprecedented strides toward quickly developing a vaccine.

As of Aug. 25, more than two dozen vaccines were being tested on humans in clinical trials and more than 135 others were in earlier stages of development, according to an analysis by The New York Times

“Having a variety of approaches is important because this is a completely new pathogen, and we don’t yet know what will work,” says Ruth Karron, director of the Center for Immunization Research at the Johns Hopkins Bloomberg School of Public Health.

If everything goes right, researchers estimate we could have at least one version of the vaccine—if not more—ready in spring 2021, according to Karron, or perhaps earlier. To put that in context, she says, “historically, vaccine development has taken 10 or 20 years.”

However, even after a vaccine goes through all the necessary testing to prove that it’s safe and effective, it still takes time to ramp up a global supply, she says. “We’ll know more by then about who the at-risk groups are and who we should prioritize to get the vaccine.”

Like the flu vaccine, a COVID-19 vaccine is unlikely to provide complete protection against the virus.

“The real goal is to protect against severe disease,” Karron says, so that even if you do get infected, you’ll be more likely to have a mild case and avoid serious complications, such as pneumonia

—Additional reporting by Lauren F. Friedman and Kevin Loria.