COVID-19: Update on Treatment

I was listening to a podcast the other day that had an economic focus on the pandemic. The interview was with an economist with experience in recession recovery. His driving recommendation was to pour an incredible amount of resources into the medical side of COVID-19: testing, contact tracing, vaccine development, treatments. If you were diagnosed with COVID-19 and could just pop a pill and it would be over, what would be we waiting for? Giddy up economy! Alas, this isn’t where we are…yet.

So, as of May 6, 2020 where are we with treatments?

1.       Antivirals: Over this past weekend, a drug received FDA Emergency Use Authorization (EUA) for use in COVID-19 patients. Remdesivir (rem-des’-uh-veer) is a medication that was initially developed and failed as a potential treatment for Ebola, and had been studied in other severe coronavirus infections, MERS and SARS. Because it showed some promise in the lab for treating the viruses causing those diseases, the drug company holding its rights began to study the effects of remdesivir on patients with COVID-19 and published its early results on Friday. The drug, given as an IV infusion, was used with patients in the intensive care unit who were very sick. The study, performed in the US and 21 countries in Europe and Asia, showed that the time it took for people to recover from their illness went down. When resources are in limited supply, it is an important result that we can reduce the number of days needed in ICUs and on ventilators. What you hope, also, is that the medication would make it more likely than not that you would survive from COVID-19 if you got infected and then treated with the drug. The study almost proved that, but it wasn’t a slam dunk. Further research with more patients may show this to be the case.

This is promising as it’s the first medication that has shown some benefit in a rigorously designed research study. While it didn’t fully prove that it saves lives, if one or our patients were very sick with COVID-19, I’d give it strong consideration.

What’s next? More research should be done to answer a few more questions about its effectiveness. Who benefits and who doesn’t? Can we use it on people who are less sick and see if it prevents their illness from progressing? Will it prevent people from dying? Can it be put into a pill form and be used for outpatients with early disease to prevent them from needing hospitalization? Still lots of questions, but this is a promising advancement that we need to build-upon.

There are also a number of other antiviral medications that are being actively studied. Antivirals are medications that directly attack the virus: nitazoxanide, ivermectin, lopinavir/ritonavir (not shown to be helpful), favipiravir, merimepodib, niclosamide, rintatolimod, EIDD-2801 (pill form!), bemcentinib, umifenovir. I am hopeful that one of these, or even one that is not listed yet, will show benefit. All we need is one.

2.       Immune system modulator, Chloroquine/hydroxychloroquine (Klor’-o-kwin/hi-drox’-ee-klor’-o-kwin): Why haven’t we heard much about these medications recently? There was initial buzz about the medication which was driven by some early reports of benefit out of France and China. These reports weren’t full-on research studies, just “hey, I tried this and look what I found” reports. While it was not good research, people got excited. In a retrospective review of VA patients who were treated with the medication, however, these drugs were shown to be potentially harmful. These two medications have the potential to cause fatal abnormal heart rhythms. A Northwestern cardiologist wrote a recent editorial in JAMA Cardiology cautioning its use, encouraging thoughtful clinical judgment and, ideally, “enrolling patients into clinical trials to provide definitive answers.” The last thing you want to do is hurt people as you’re trying to help them.

I’m not sure the full story of this medication has been told yet, though. Ongoing studies are looking at hydroxychloroquine in other populations of patients. Perhaps it could be used for prevention after exposure? As an early treatment? What we do know, though, is that monitoring the heart rhythm in some way will be required.

3.       Immune system modulator, IL-6 inhibitors: This is another class of medications for seriously ill COVID-19 patients. You may have heard of the cytokine storm that can happen to some severely ill COVID patients. When the “storm” hits, the body’s immune system is on overdrive. If an antibody is a smart bomb, the cytokine storm is a self-detonated nuclear bomb, destroying everything in its path. Can you stop the destruction of a nuclear warhead? Maybe.

Tocilizumab (Actemra) and sarilumab (Kevzara) are medications used in people with autoimmunity, diseases where a person’s body fights against their own tissues and can result in a cytokine storm. There are ongoing studies, including at Northwestern, looking at the potential benefit of IL-6 inhibitors in slowing this cytokine storm in COVID-19 patients. Early research has shown that this approach could bear fruit. While these drugs may help, experience has shown that they aren’t without their own complications, with side effects including an increase in certain types of cancers, liver and nervous system problems, severe allergic reactions and others. The benefits and risks need to be balanced appropriately, ideally as part of a clinical trial.

4.       Immune system modulator, Convalescent Plasma: The blood circulating in our bodies is make up of cells (about 45%) and plasma (55%). The cells include red blood cells, the microscopic taxis that ferry oxygen around, white blood cells, the backbone of our immune system, and platelets, key components of our blood clotting system. Plasma is everything else in our blood: water, minerals, vitamins, fats, proteins, etc. Some of those key proteins are antibodies, which we have learned a lot about recently. These antibodies are the laser guided smart bombs of our immune system, targeting specific foreign actors – aka antigens – for destruction. In recovered COVID-19 patients, these antibodies could be a key weapon in our arsenal for treatment of others.

Did you know you could donate plasma? Just like we can donate “blood”, we can also donate plasma, and it’s actually easier and can be done more often than donating blood. You don’t hear much about donating plasma because we don’t use it for a lot of reasons. We DO use the red blood cell portion a lot, for people who have had traumatic injuries or who are undergoing surgery where there is a loss of blood. Plasma, on the other hand, doesn’t have a ton of indications. For COVID-19? Maybe, ya. If someone is really sick with COVID-19 and trying to fight if off, perhaps the proteins and antibodies from someone who HAS recovered from it could be useful to their recovery. The FDA has offered guidance for using convalescent plasma, and the University of Chicago Medicine has an active study on its use. If you or a friend or family member has had confirmed COVID-19 and is interested in helping, this is an option for you. Reach out.

Again, this isn’t something for early stage disease or minimally symptomatic people. We need to keep working to find those solutions.

5.       Other treatments under investigation:

a.       Immune modulators: Steroids such as prednisone, methylprednisolone, and others are not recommended by the WHO for treatment of COVID-19 or other viral pneumonias. That being said, studies are ongoing. I would strongly consider not using these drugs in people who aren’t severely ill with strong potential for the cytokine storm. Steroids suppress the immune system and you need your smart bombs at the start.

b.       Immune modulators, Statins. Our patient who was in the ICU and on a ventilator came home on Sunday to his “second life.” One medication he was on before admission, a statin, had been boosted from 5mg to 20mg. “Why,” I thought? There is an increased risk of death in COVID-19 patients with heart disease, so it could have been preventive. Perhaps because statins decrease the inflammation associated with heart/vascular disease, and there is some suggestion that it could be beneficial for COVID sufferers, too. All that being said, if you should be on a statin for cholesterol it is a very good idea to stay on it.

c.       Other immune modulators: There may be a role for inhaled nitric oxide for severely ill people on ventilators. JAK and NAK inhibitors may prevent the virus from entering the cells in the first place. There are dozens of other drugs in the immune modulator category that are being studied.

d.       Antacid famotidine/Pepcid: An initial report out of China showed that some nursing home patients taking the medication did better with COVID-19. It was just an observation not a well-designed study, so a NYC hospital in April began studying it in high doses for hospitalized patients. Of course, when word got out, supplies dwindled. Hoarders. We don’t know anything yet, so don’t make famotidine the next toilet paper. (Also, don’t take it’s cousin, ranitidine/Zantac. Those drugs should be off the market, pulled because of contamination of the medication with NDMA, a chemical that could cause cancer.)

The purpose of this review has been to give you an overview of what is out there with regard to treatment of COVID-19 as of May 6, 2020. Remember: our goal is to NOT get infected in the first place! Stick to shelter at home for now, wear a mask if you have to go out, keep your hands meticulously clean, and don’t let anyone into your six-foot-zone-of-safety, even with a mask on. As we relax the stay at home measures, a heightened focus on prevention will be key. The longer it is before you get sick, the greater the chance that one of these medications will have been shown to be a true game changer.

Stay safe.

More to come,

Dr. Will