Diagnosed or been exposed to COVID-19? New studies are testing desperately needed therapies.

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Editor's Note: The information published in this story is accurate at the time of publication. Always refer to uab.edu/uabunited for UAB's current guidelines and recommendations relating to COVID-19.

rep covid trials plasma donor 550pxDonations of plasma from patients recovered from COVID-19 are being used to boost the immune systems of newly infected individuals using convalescent plasma therapy, one of three treatments being studied in new outpatient clinical trials at UAB.It is the call no one wants: On the other end of the line is a doctor telling you that you have been diagnosed with COVID-19 or a loved one who has tested positive.

What can you do now? (If you are a UAB employee or student, you should report a potential high-risk exposure, and a positive test, if it was not conducted at UAB, on your daily Healthcheck. But what then?)

For the first several months of the pandemic, there has not been much that doctors could do for patients outside the hospital, said Turner Overton, M.D., director of UAB's outpatient COVID-19 clinic and professor in the Division of Infectious Diseases. Inpatients at UAB can receive the antiviral drug remdesivir or the steroid dexamethasone if they are having difficulty maintaining sufficient oxygen levels. UAB is participating in several other studies of treatments that are open to inpatients. But there have been no targeted treatments for patients diagnosed with COVID-19 if they are not sick enough to be hospitalized.

"We have all these people who are having symptoms, and we really have very little to offer them, unfortunately," Overton said. "It's really symptom management to help people get through and try to prevent hospitalization or identify those people who will need hospitalization so they can get access to remdesivir or dexamethasone as early as possible."

But now three new clinical trials are underway at UAB that make experimental therapies available to people in the first days after symptoms begin. One is even testing a preventive treatment for people who have been exposed to the disease but do not have a COVID-19 diagnosis.

Transferring immunity

"When we think about ways to treat COVID-19 we can either target the virus using antivirals, such as remdesivir, or we can use the immune system to target the virus," said Sonya Heath, M.D., professor in the Division of Infectious Diseases. "The studies we are enrolling for now use the immune system to block the virus and help to eliminate it.”

How to enroll

To learn more about participating in any of the trials discussed here, or to find out if you are eligible, call (205) 934-6777.

It is now clear that “the patients who do better with COVID-19 are the ones who generate an immune response to the virus,” Heath said. “They have a shorter course of illness and their viral load is lower. [Viral load is a measure of the amount of virus particles in an infected person’s body.] We know that generating an immune response to the virus is a good thing and decreases your symptoms and your severity. Each of these studies is looking at ways to transfer an immune response to you in some form."

Who can participate?

Who is eligible to participate in these trials? It all depends on where a person is in the course of their infection — or if they have a high-risk exposure to someone with COVID-19.

rep covid 8 days 413x550pxIf it has been eight days or less since symptoms started:

Convalescent plasma outpatient study: With convalescent plasma, "we are taking plasma — the liquid portion of the blood — from somebody who has recovered from the virus and transferring that immunity to someone actively infected with the virus now," said Heath, who is principal investigator for this study. "We've been doing this since early summer for inpatient care and now we are using it with outpatients." The inpatient study showed that plasma with high concentrations of antibodies against COVID-19 was most beneficial, Heath said.

The new outpatient study will treat half of the patients enrolled with an intravenous (IV) infusion of plasma that has high antibody concentrations. The other half of study participants will receive a placebo — plasma from someone who has not had COVID. "We are asking the question: If you give high concentrations of antibody is that beneficial in decreasing severity of illness and decreasing the likelihood that somebody will be hospitalized?" Heath said.

Learn more about convalescent plasma therapy and the trial in this story from the UAB Reporter.

If it has been 10 days or less since symptoms started, or seven days or less since you had a positive COVID-19 test:

rep covid 10 days 550x413pxInstead of using antibodies from donors who have recovered from COVID-19, several pharmaceutical companies have identified very strong antibodies against the virus and are making them in their labs. The companies Regeneron and Eli Lilly have each developed their own synthetic antibodies, known as monoclonal antibodies. "The preliminary work from both of these shows that they are effective," Overton said. "If we can get people these monoclonal antibodies early on in their illness, we can really mitigate the long-term effects of COVID-19. If we can stop the virus in its tracks in the first three or four days then we can potentially block the consequences."

Regeneron trial

Regeneron's experimental therapy was given to President Trump during his recent hospitalization. "This is a cocktail of antibodies — a combination of two different antibodies targeting proteins on the surface of the virus," Heath said. "If it can bind to the virus it can help eliminate it and reduce the severity of the illness."

Do you have to live in the Birmingham area to take part?

No, Heath said. "Many of these studies have been designed to limit the number of in-person visits," she explained. "For example, with the convalescent plasma study we see people on day 1, day 14, day 28 and day 90 and everything else is done by phone. For the Regeneron trial you get one infusion and then you have a few in-person visits but a lot of it is done by phone or a log that you keep."

Participants in the Regeneron Phase I outpatient trial at UAB are randomly chosen to receive a high dose of the antibody cocktail, a low dose of the antibody cocktail or a placebo. "It is a one-time infusion," Heath said. "There are significant reductions in the viral load with both the low-dose and the high-dose infusions."

Although the UAB trial site is just opening, Regeneron has released early reports on the first 275 patients who enrolled in the trial at other locations, and these included "some beneficial outcomes," Heath said. These include reduce viral levels and improved symptoms, according to the company.

ACTIV-2 (Lilly) trial

This trial is testing a monoclonal antibody developed by Eli Lilly. "Participants will receive either placebo or the monoclonal antibody from Lilly that attaches to the virus and blocks it from infecting cells and causing disease," said Overton, who is principal investigator at UAB for the trial. "Compared to the Regeneron trial this monoclonal antibody has not gotten as much press but it is a similar monoclonal antibody that has been shown to be effective in the preliminary Phase I and II trials."

"We have a great deal of experience using this immune-based approach," Overton said. "Furthermore, it's a proof of concept for vaccines. If the passive immunization strategy works with either convalescent plasma or with monoclonal antibodies, it really gives a lot of strength to pursuing effective vaccines."

Sonya Heath Turner OvertonInfectious diseases specialists Sonya Heath, M.D., and Turner Overton, M.D., explain the new trials to the media in this screenshot from UAB's virtual press conference.

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Treatment or placebo?

Each of the trials mentioned here includes a treatment arm and a placebo arm, meaning that some participants will be chosen at random to receive an infusion of the active drug (or convalescent plasma) and some will receive an infusion of inactive saline instead.

Why use placebos? Because the progression of COVID-19 is varied and difficult to predict. Many patients who initially feel poorly recover within a few days. Without a placebo arm of the trial, it would be impossible to know whether that recovery was due in part to the treatment, or would have happened anyway.

If patients receiving treatment show better outcomes than patients receiving placebo, that will give doctors crucial information to indicate that the treatments are effective.

But it is important to note that participants who receive a placebo are not missing out on another type of treatment, Heath said. "Participants will receive the standard of care for treatment of COVID-19," she said. "Participating in these trials does not prevent you from getting any of the standard therapies that would be indicated for your treatment. If you are in one of our outpatient trials and you become sick enough to go into the hospital and the provider caring for you thinks that you would benefit from steroids or remdesivir, you are certainly eligible to get that as part of the standard of care."

rep covid 4 days 413x550pxIf it has been four days (96 hours) or less since you were in close contact with someone diagnosed with COVID-19:

People who have been closer than six feet from a person diagnosed with COVID-19 for more than 15 minutes during a 24-hour period are considered to be "close contacts." If you meet these criteria, you may be eligible to take part in a UAB study testing convalescent plasma therapy as prevention.

The idea is that an infusion of antibodies from a recovered COVID-19 patient could give your body a head start in fighting off the disease and reduce the risk of having serious complications from COVID-19.

"We have some people who live in a household where they don't have multiple bathrooms and it is hard to quarantine away from elderly parents," Heath said. "They might try to get one person in the household treated with the outpatient treatment [either convalescent plasma or the Regeneron or Lilly monoclonal antibody trials] and then other people in the household who are COVID negative could take part in the prevention phase to really try to see if we can intervene on the severity of illness in their family."

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What are the side effects?

Convalescent plasma: "We have been doing this for a long time, since the 1800s," Heath said. "When we think about our blood supply in the United States, it is very safe. We test for infectious diseases like HIV, hepatitis C, hepatitis B and a number of other diseases. When we had West Nile Virus floating around, we tested for that as well. A plasma transfusion is even safer than blood. You are only getting the liquid portion of the blood and not the cellular portion, so the possibility of any reactions is even more reduced. We do these convalescent plasma treatments in our infusion unit at UAB. If anybody has a fever related to the transfusion, we would give Tylenol, but we haven't had that happen. We are also watching for itching but we really do not have significant issues with people receiving the transfusions."

Monoclonal antibodies (Regeneron and Lilly trials): In the first 275 patients treated in the Regeneron trial (this did not occur at UAB), there were a total of four transfusion reactions, Heath said. "Two were in the placebo group, one was in the low-dose group and one was in the high-dose group,” she said. “They were all mild reactions, which [trial scientists] considered to just be related to receiving an infusion. Just like when you get your flu shot you may have a little redness around the area or tenderness. We do monitor for transfusion reactions but what we've seen in the study is that it is very safe."

"One of the things we do is infuse relatively slowly and monitor the person in the infusion center for two hours after the infusion as well for added safety," Overton said. "We are confident that this is a safe therapy."

It is also important to note that Regeneron and Lilly have experience creating antibody-based treatments for other conditions, including Ebola, cancer, ulcerative colitis, rheumatoid arthritis and more, Heath and Overton said. "What this means is that the platform they are building on is the same one that has been tested in thousands and thousands of people," Heath said. "The only thing that is different in these situations is that the antibody is directed against this spike protein" in SARS-CoV-2, the virus that causes COVID-19.

‘Consider participating in these trials’

After a COVID-19 diagnosis, "people are scared and they don't know what to do — sometimes not doing anything when you feel sort of bad but not terrible seems like a reasonable approach," Overton said. “But we don’t know who is going to get worse disease. We know there are certain individuals — older people, people with certain comorbidities — who are at greater risk for severe disease, but I can tell you that we see healthy people getting severe disease as well. So we are really encouraging anybody who is interested to get involved. There may be some benefit for them and without treatments and vaccines we will be stuck in this situation that we are in."

Trials and triumph

During the past five years, UAB’s clinical trials portfolio has more than doubled. That means more potentially life-saving treatments for cancer, heart disease and many other conditions are available to Alabamians — in addition to the COVID-19 trials described here. Find out how this amazing growth happened.