Coronavirus Treatment: Does It Already Exist?

Do we already have a treatment for coronavirus (COVID-19)? Is President Trump right about chloroquine or is redesivir more promising for coronavirus? The biopharmaceutical industry is working to see if currently available medications could treat the illness COVID-19 causes. It’s important to note that drugs cannot be a cure for CO​V​ID-19 because viruses can’t be permanently stopped by anything but your own immune system. ​But treatment​s​ ​are being developed to address both the virus and the damage it causes.

A Two-Pronged Approach

So far, it looks like around 15% of patients infected with COVD-19 develop severe illness that requires hospitalization, and another 5% need treatment in the intensive care unit (ICU). One approach to treat COVID-19-related illness is to find medications that slow down — or even stop — the virus’s ability to reproduce. This could shorten the length of illness and prevent it from becoming severe or critical.

Researchers are also investigating drugs that stop the body’s autoimmune response in the critical stages of illness. If patients progress to severe illness, they can develop acute respiratory distress syndrome (ARDS), which isn’t caused by the virus, but by the body’s inflammatory response to it. Most of the deaths attributed to COVID-19 are from ARDS, so finding ways to reduce or halt the inflammatory response could result in fewer deaths.

It’s important to note that there isn’t enough scientific evidence about the safety or effectiveness of any of these drugs for them to have been approved by the U.S. Food & Drug Administration (FDA) to treat COVID-19. Larry Sasich, PharmD, MPH, a consultant for the FDA and the Saudi Arabian Food and Drug Authority, and co-author of Worst Pills, Best Pills, also points out that the side effects that we know about are in people who don’t have COVID-19.

Because we don’t know much about what can safely or effectively treat COVID-19 yet, it’s important to talk to your doctor about any medication that you’re considering using for COVID-19. Not only is there the possibility for dangerous side effects, but there are also potential drug interactions to consider, so it’s important to have medical supervision.

While we are a long way from having any definite answers yet, the fact that clinical trials are going on during a pandemic is encouraging.

Potentially Promising Treatments

Here’s a look at some of the drugs scientists are researching to see if they could be effective in treating COVID-19-related illness.

Antiviral Drugs

Remdesivir

Remdesivir was originally formulated to fight Ebola. However, it was found to be basically ineffective against the Ebola virus during the 2019 outbreak in the Democratic Republic of the Congo.

What it’s currently used for: Remdesivir works by inhibiting a virus’s ability to replicate, but it isn’t approved to treat any type of condition or disease.

Clinical trials: There are three large-scale clinical trials going on in the United States to look at the effects of remdesivir in patients who are hospitalized with severe COVID-19-related illness. Other trials are going on worldwide as well, including a large global trial by the World Health Organization (WHO) called SOLIDARITY that’s testing four different drugs, including remdesivir.

The drug manufacturer, Gilead, has been flooded with requests for individual use as well but is recommending that people enroll in a clinical trial instead if at all possible.

Known serious side effects: Not a lot of information is available for this drug since it’s unapproved and only experimentally used. “One concerning bit about it is it does have a solubilizing agent in it called sulfobutylether-beta-cyclodextrin (SBECD),” says Michael Klepser, PharmD, FCCP, a professor at Ferris State University’s College of Pharmacy. “We’ve seen that solubilizer used with other medications and sometimes in patients with renal dysfunction, it can cause some problems because (the SBECD) can accumulate and cause kidney damage. That would be the major thing to keep an eye on.”

How it could help COVID-19 patients: In 2017, researchers found that remdesivir was effective against many different coronaviruses — including the ones that cause severe acute respiratory syndrome (SARS) — in both a mouse and in cell cultures. Two patients in the United States with COVID-19 were given remdesivir when the outbreak first started and have recovered.

“The idea is treating with remdesivir would prevent the viral infection from becoming established and would also shorten its duration once it’s already happening,” says Hana Akselrod, MD, an assistant professor of medicine in the infectious diseases division at the George Washington University School of Medicine and Health Sciences. “What’s not known with remdesivir is how effective it is because it was not originally developed for this specific virus. There have never been large numbers of patients treated with it, even with Ebola, and how it will perform against the novel coronavirus that causes COVID-19 is what’s being investigated right now.”

“This is one that I’m fairly excited about,” says Klepser. “I’m anxious to see some of the information from trials. This is the medication that most patients might end up having access to before trials.”

Potential risks for COVID-19 patients: “There are questions of what (remdesivir’s) potential toxicities and side effects will be, how it’s metabolized, what’s the correct dose to give, and when in the course of illness it would be most effective. And would it possibly interact with other drugs that the person is receiving?” Akselrod says.

Gilead plainly states on their site that remdesivir “has not been demonstrated to be safe or effective for any use.”

Ritonavir and Lopinavir

Ritonavir and lopinavir are antivirals used in a combination drug called Kaletra.

What it’s currently used for: Kaletra is FDA-approved to treat human immunodeficiency virus (HIV). This medication blocks the virus’s ability to copy its genetic material, says Akselrod. “This is a medication we’ve been using for many, many, many years to treat HIV and it’s a potent and effective antiviral, but for a virus that’s not in the same family as COVID-19,” she says.

Clinical trials: Kaletra is another drug being studied in WHO’s SOLIDARITY study, as well as Kaletra combined with interferon-beta.

Known serious side effects: There are a number of other medications that shouldn’t be taken with Kaletra because of the risk for serious drug interactions. Kaletra can also lead to pancreatitis, liver damage, heart rhythm abnormalities, increased cholesterol levels, and new or worsened diabetes.

How it could help COVID-19 patients: “It did show some potential promise against the novel coronavirus in laboratory studies where they tested in an artificial laboratory setting or in an animal model,” Akselrod notes. “There were reports of it being used clinically, from the early days of this epidemic.”

However, a recently-published clinical trial in China used Kaletra to treat COVID-19 patients hospitalized with pneumonia and the researchers found that it wasn’t effective. “For a drug that’s supposed to block the production of the virus, at least in that study, it didn’t seem to do much,” says Akselrod. “There are still other studies ongoing and we’re all keeping our ear to the ground on that.”

“The advantage with ritonavir/lopinavir is that it is widely available. It’s been around for many years, so there are ways to produce it on a mass scale to ensure quality,” Akselrod says. “And we also know how it behaves in terms of metabolism. It does have interactions with other drugs, which is a big caveat, but at least we know what those interactions are, whereas for a newly developed drug or for a drug that has never been tested in a large human population, we might just not know what those complications would be.”

Potential risks for COVID-19 patients: As with all these drugs, the potential risks for COVID-19 patients specifically are not clear but include unknown dosing and unknown duration of medication use. The only solid information we really have is “what’s in the professional product label for patients who don’t have COVID-19,” says Sasich.

Malaria Drugs

Chloroquine and Hydroxychloroquine

Update: on March 30, 2020 the FDA granted chloroquine and hydroxychloroquine “emergency use authorization” for the treatment of COVID-19. The FDA did NOT approve these two drugs as a treatment for COVID-19. The approval was made so that the government could add it to the Strategic National Stockpile and it would be available for hospitals to request and to supply for clinical trials.

What they’re currently used for: These medications are both approved by the FDA to treat and prevent malaria. “Remember that malaria is not a virus or a bacterium, it’s a parasite,” says Sasich. Because parasites have cells that are similar to human cells, a drug that’s used to treat a parasitic infection like malaria may cause more serious adverse effects, he says.

Chloroquine is also approved to treat amebiasis, a gastrointestinal infection caused by an amoeba. Hydroxychloroquine is approved for systemic lupus erythematosus and rheumatoid arthritis in patients whose symptoms haven’t improved with other medications.

Clinical trials: There are several clinical trials scheduled or planned in the United States to test out these drugs as a way to prevent or treat COVID-19. Chloroquine and hydroxychloroquine are also part of WHO’s SOLIDARITY trial.

Known serious side effects: Chloroquine’s potential adverse effects include cardiomyopathy (heart muscle disease) that can result in heart failure, heart rhythm abnormalities, severe hypoglycemia (low blood sugar), permanent eye damage, muscle weakness, and many adverse effects on the central nervous system. Using chloroquine with certain other medications can lead to serious drug interactions. Other side effects have been reported since this medication was approved too.

Hydroxychloroquine has a risk of similar serious side effects such as permanent eye damage, cardiac effects like cardiomyopathy with a risk for heart failure and heart rhythm abnormalities, severe hypoglycemia, and muscle atrophy. It can also cause suicidal behavior. Other serious effects have been reported since this medication was approved as well, including disorders of the blood, heart, ear, eye, immune system, metabolism, and skin.

How antimalarials could help COVID-19 patients: Akselrod says the theory is “essentially (that) those drugs would make the cell less hospitable to the virus by interfering with some of the mechanisms that are involved in both the virus entering the cell and then possibly with the inflammation that occurs around the infection.”

Like remdesivir, chloroquine and hydroxychloroquine have been found to be effective against coronaviruses in cell cultures, including ones that cause SARS. However, it’s possible that high doses may be needed for the drugs to be effective enough, which can cause serious side effects.

It’s also unknown “how effective they are in both preventing infection from occurring and for preventing the infection from becoming severe if it does occur,” says Akselrod. “Right now, different medical centers around the U.S. and the world are trying protocols of treatment with these, but they’re doing it under medical supervision and in controlled doses and for patients that are selected for whom we think they will be beneficial and also safe. I think it’s going to take real worldwide collaboration to answer this question on a mass scale.”

Potential risks for COVID-19 patients: Since there aren’t any clinical trial results to guide them on treating COVID-19, doctors have no way to know how much medication to prescribe or how long to prescribe it for.

Not just anyone can take them either, Akselrod says. “Chloroquine and hydroxychloroquine can cause quite severe poisoning and even fatalities if they’re not taken under the supervision of a doctor or if they’ve taken in the wrong dose or if they’re taken by someone with a heart condition that’s predisposed to an irregular rhythm. These drugs can cause an unstable heart rhythm, which can cause the heart to stop, which is why it’s so concerning that right now there seems to be a worldwide rush on these drugs.”

“The major concerns with these medications are their toxicities and that when they’re used, some patients experience very severe side effects, including cardiovascular conduction abnormalities and agranulocytosis, which is kind of like wiping out your immune system” Klepser says. “Where I’m at with this is all these people that are thinking that this is a good medication to have on-hand just in case, this is not something that I would give a family member ‘just in case.’ If I had somebody that I was concerned about with documented COVID-19, then I may consider using it, but this is not going to be wide-use empiric therapy because (of) the side effects associated with it.”

People hoarding these drugs or taking them unsupervised is becoming a problem too, says Akselrod. “This is in the context of an unprecedented global emergency and it’s quite understandable if people are scared and trying to reach for anything that’s available that we think might help. But people who depend on these drugs to control their lupus or rheumatoid arthritis find themselves unable to refill their prescriptions. They’re at risk of having their disease flare up and force them to go to the hospital at a time when it’s very unsafe for them to be doing that and when they should be isolating at home and trying to avoid infection at all costs.”

The bottom line: These medications should not be taken unless your doctor has prescribed them for you, and you’re under medical supervision. They shouldn’t be taken to prevent COVID-19 either. Non-medical forms of these drugs aren’t meant for humans and are dangerous.

IL-6 Receptor Inhibitors

IL-6 (interlueukin-6) receptor inhibitors tocilizumab and sarilumab are both injections and “they are quite potent in reducing inflammation,” says Akselrod.

Tocilizumab

What it’s currently used for: Tocilizumab (Actemra/RoActemra) is FDA-approved to treat active rheumatoid arthritis, giant cell arteritis, juvenile idiopathic arthritis, and cytokine release syndrome. It works by decreasing the overactive inflammatory response found in these conditions.

Tocilizumab was recently approved in China to treat COVID-19 patients with severe lung damage. “We’re waiting with bated breath to see what the results of that are,” Akselrod says.

Clinical trials: Tocilizumab’s manufacturer, Roche, is putting together a global trial to test the drug in COVID-19 patients with pneumonia starting in early April.

Known serious side effects: Tocilizumab has multiple potential side effects, the most serious of which is a black box warning. “A boxed warning is the most serious warning that the FDA can require in the professional product label for a drug,” says Sasich. “Usually it involves deaths in human beings.” In this case, the boxed warning is for an increased risk of developing serious infections that can lead to hospitalization or death.

Other severe adverse reactions include tears in the stomach or intestines, liver issues, low platelet count, higher blood cholesterol levels, low neutrophil (white blood cell) count, allergic reactions, and an increased risk of cancer.

Sarilumab

What it’s currently used for: Sarilumab (Kevzara) is FDA-approved to treat active rheumatoid arthritis (RA), particularly in people who haven’t responded to other medications for RA or who can’t use other types of medication.

Clinical trials: A clinical trial for sarilumab was started in New York in March by the drug’s manufacturer, Sanofi and Regeneron Pharmaceuticals, to test the drug in hospitalized COVID-19 patients.

Known serious side effects: Sarilumab, too, has a black box warning about an increased risk of developing serious infections that can lead to hospitalization or death. It also has the same potential serious adverse reactions as tocilizumab, including tears in the stomach or intestines, liver issues, low platelet count, higher blood cholesterol levels, low neutrophil (white blood cell) count, allergic reactions, and an increased risk of cancer.

How IL-6 inhibitors could help COVID-19 patients: The theory is that these medications “try to block parts of that severe immunologic inflammatory cascade in order to reduce the severity of the pneumonia that happens after the virus (COVID-19) has already caused the infection,” Akselrod says.

“There do appear to be some data that suggest that (Il-6 inhibitors) might be effective as adjuncts to treatment in patients with severe COVID-19 pneumonia, reducing some of the inflammation and some of the other complicating factors, hopefully, to improve oxygenation,” says Klepser. “They’re not going to necessarily cure the virus, but they may help patients improve clinically.”

Potential risks for COVID-19 patients: “What we don’t know is, in the context of viral infection, is it safe to block that inflammation? If you block the inflammatory or immune response early, you might actually hamper the body’s own ability to fight the virus,” says Akselrod. “We think if we do it too late, then the damage is already done, and it won’t make a difference. So that window of opportunity to intervene with IL-6 inhibitors, that’s undefined right now.”

Another potential risk that needs to be explored involves the black box warnings about an increased risk of severe infection. “The trick is to figure out if IL-6 inhibitors can be used safely to tone down the damaging parts of the immune response without shutting down the parts of the response that are needed to fight infection,” says Akselrod.

The infection risk also means that “these are probably not going to be what you see used in the majority of patients, but maybe in the sickest of the sick,” notes Klepser. He also points out that these drugs are quite expensive, though he acknowledges that “at this point in time, I’m not sure that cost is really that big of a consideration.”

Convalescent Plasma

The FDA is supporting research on using the plasma from people who have recovered from COVID-19 to treat patients infected with the virus. The theory is that this plasma holds antibodies that could be used to help others with COVID-19 recover.

One study has been released that has only five people in it, with no comparison groups. Therefore, it’s not a good quality study. However, it’s an indicator and it offers some hope. Five people (two women, three men) who were critically ill with ARDS brought on by COVAD-19 were given infusions of convalescent plasma from recovered patients. All five recovered.

“This approach predates a lot of the current science on vaccines in immunology and the antibody response,” says Akselrod. “For more than 100 years people have tried this approach in trying to use the blood of people recovered from an infectious disease to cure those still suffering from it. The promise is that there is historic experience with it. The downside is, of course, we don’t know how effective it will be for this virus, in part because there might be slight variations in the virus that circulates across the big population. Viruses do mutate and change their surface appearance in ways that try to evade the immune system.”

“It’s an unknown and it’s a type of therapy that has been used in the past. I think it’s definitely worth a try. It’ll be interesting to see how studies turn out,” says Sasich. “We don’t know how rapidly the COVID-19 virus may mutate. That’s always the problem. It may be a moving target.”

“Theoretically, we’ve done that (convalescent plasma) in the past for a lot of conditions where we didn’t have good therapies,” Klepser says. “There’s still that controversy — do people generate a strong immune response when they’re infected? I think they probably do, but there’s some data of people getting re-infected. Whenever you start using these blood products, depending on what the manufacturing process is like, there’s always a potential for bloodborne pathogens, a variety of side effects, fluid overload, allergic reactions, and stuff like that. Again, we’re in a time when things I would normally do kind of fall off my map right now just because you’re in a position where when there’s nothing to lose, you try things. And for some patients, we’re at nothing to lose, so to have that available might be helpful.”

“I think the major limitation of using immunoglobulin from recovered patients is that the supply is not going to be very high,” says Akselrod. “Transfusion reactions are possible with any blood product because you’re giving someone else’s biological product. The recipient’s immune system might not like it and they might have a severe reaction to the transfusion, which is why it has to occur under supervision. The limitation will be both in the supply and in the distribution, administration, and safety.”

“We also don’t know what magnitude of effect to expect from this treatment, but again, we’re facing an unprecedented emergency. And while we’re all trying to buy time for scientists and medical researchers to come up with truly new treatments and test them, maybe (convalescent plasma) can help protect at least some of the people who are currently ill,” Akselrod says.

Three Top Docs’ Opinions

Hana Akselrod, MD

MD, an assistant professor of medicine in the infectious diseases division at the George Washington University School of Medicine and Health Sciences

“My first advice is do not panic. It’s a completely unprecedented challenge for all of us, but there are fantastic people on the front lines of it in clinical medicine and in science and on the patient advocacy side and together, we will rise to the challenge on this. I think there is a rich history of patients and physicians and scientists coming together to solve these world-changing diseases. I’m thinking of polio and HIV and smallpox and malaria — we’ve been able to either defeat or control these diseases to the point that either they’re gone from humanity, like smallpox, or we’ve made them treatable and manageable, like malaria and HIV. We’ll get there.

“Right now we’re just in this surge phase where we’re going to see a lot of people get sick at once and we’re trying to space out when that happens, both to preserve our ability as doctors and nurses and health workers to treat people with the resources that we have, and to buy time for medical science to establish which drugs are useful and which drugs are safe.

“For people who are facing a diagnosis of COVID-19, I would recommend that they look at what is available where they are, and ask their doctors and their local medical community if they could be in a trial to get access to a new treatment to help us as the American people, and as a world society, to come to more knowledge on this disease. We have to develop new science and safety-test it and then distribute it to the people that it will help the most.

“To everyone else, whether they’re worried about COVID-19 or know someone who has been diagnosed, or whether it’s just coming to where you are, wash your hands. Observe social distancing. Help us spread the cases out. And do what you’ve got to do to keep yourself and your family healthy and safe.”

Michael Klepser, PharmD, FCCP

PharmD, FCCP, a professor at Ferris State University’s College of Pharmacy

“I’m jumping all over the clinical trial. If it’s me and they said you could potentially get this antiviral, which has shown to have some efficacy, I’m in. Do I want to be treated with hydroxychloroquine? Not really, but if it’s life or death, yeah. I would not be looking at the internet for home remedies. If there is a clinical trial, I’m in. Specifically, if I can get in the Gilead trial with remdesivir, I’d probably really want to get in that one.

“With respect to medications, the big thing still with this disease is the medications are going to be helpful, but they’re not going to reach everybody. Now just from the scope of what we’re predicting for this disease in the next several months, these medications are not coming to market. These medications are not going to be able to get FDA-approved and they may be available for emergency-use authorization, but most likely through clinical trials.

“The best thing is still to be smart, adhere to guidelines for social distancing, and stay at home. And still there’s a lot of people that take that relatively lightly. Think about not just what your exposure is, but anytime you make an exception to an exposure, you have now become exposed to everybody that other individual has been exposed to. And it only takes one time letting your guard down to get infected.

“Also, know that there’s still a lot of influenza out there, there’s still other infections. So, if you can get an influenza test still, rule that out. If you can get an influenza vaccine, get it. These things are going to help the picture be a little bit clearer. Get your pneumococcal vaccine; that’s one of the pathogens that causes some of the super infections. Get that before you get infected with COVID-19.”

Larry Sasich, PharmD, MPH 

PharmD, MPH, a consultant for the FDA and the Saudi Arabian Food and Drug Authority, and co-author of Worst Pills, Best Pills

“When it comes to treatment and/or participating in clinical trials, if it’s being sponsored by a reputable company, like a major drug manufacturer, or a major research institution, and the purpose of the trial is to gain regulatory approval and there is a well-written, informed consent form outlining all of the potential risks, that’s a personal decision on the part of the patient that wants to participate. There are none of these drugs that I would recommend the patient take at this time; there are just too many unknowns.”

 

Transferred linked: https://www.medshadow.org/coronavirus-drugs-do-we-already-have-the-cure/