I want a new drug!

This post will answer these questions:

1. What medication should I take if I’m home with the coronavirus?
2. Is ibuprofen dangerous?
3. Are there any cures?
4. Does the malaria drug chloroquine work for the coronavirus?
5. What about hydroxychloroquine?

Today is a big day for me. It’s day 6 since I developed symptoms. In the cases of severe disease, most started developing shortness of breath by day 6. Today I feel better. The cough makes my sleep terrible, but the aches are better and I haven’t had a fever in 3 days (although the cabin fever is starting to accelerate). I have been able to control most of my symptoms with a combination of over the counter remedies that has kept me functional and minimally symptomatic. I have been getting many questions and reading many articles about treating COVID-19 so I wanted to summarize what I’ve learned.

As is often the case, when you have an illness that generates a great deal of anxiety people will tout the benefits of all sorts of remedies for financial or other gain. Snake oil salesmen love a good pandemic. These are the times where science is important. These medications can often give false hope although they are not effective. Even worse, they can lead to unforeseen side effects. Just because something is labeled as “natural” or “healthy” doesn’t mean it’s safe. Science is just another term for the methods used to prove something is safe and effective. To truly prove something is effective often requires time and effort. In a time like this, people want to know now. Unfortunately it doesn’t work like that.

The next thing to understand is how to approach the decision to prescribe a treatment. These decisions come down to an assessment of the risk (e.g. side effects) of a medication relative to the benefits of the medication (e.g. how it improves symptoms, morbidity, or mortality). When the benefits outweigh the risks, I will recommend the medication, if not, I won’t.

Another way to approach this is to ask, ‘What is the risk of taking the medication?’ and ‘What is the risk of not taking the medication?’.

Sounds like an easy calculation but it’s not. The problem is that the risks and benefits are not usually clear. We have to factor in the level of uncertainty when making the decision. Our estimates are often not precise and we are forced to make educated guesses. No situation is a better example of that than the one we’re in now. It takes sometimes many years to accrue the data from multiple expensive research trials to tease out the ratio of risk to benefit. We’ve been at this for only a few months.

The way I see it, the starting point with the coronavirus is to accept that the vast majority of people will have mild to moderate disease and will recover completely. For them, the benefits of treatment will be to minimize symptoms and perhaps speed recovery if possible. While these are noble goals, they do not justify taking great risk or accepting great uncertainty. For people with severe disease, it is an entirely different story. For them, we should willing to take on more risk and deal with more uncertainty because of the potential life saving benefit. To make it a bit complicated (if you’re head wasn’t spinning enough), the patients who are sicker are usually more susceptible to the side effects making the risks higher.

This could all change tomorrow, so take that as a caveat. Of course, you should check with your doctor if you are concerned and always follow the instructions on the label.

Acetaminophen (AKA Tylenol)

This one is easy. The risk of harm is low unless you are a heavy alcohol drinker or have liver disease. Although it is not clear how it does it, acetaminophen is good at lowering fever and easing aches and pains. I have been taking it every 6-8 hours and am grateful to have it.

Ibuprofen (AKA Motrin or Advil)

This one is a bit strange to me. For some reason it has gone viral (can I use that term anymore? I feel like we may need to find an alternative) that ibuprofen is deadly in coronavirus. It was all started by a tweet by the French health minister Olivier Veran after some French COVID-19 patients had experienced serious side effects. It would take too long for me to explain why coming to a conclusion of harm from the experience of a few patients is ridiculous but just take my word for it, it is. Not four days later the European Medicines Agency (their FDA) said that there was “no evidence establishing a link between ibuprofen and worsening of COVID‑19”. The WHO tweeted, “Based on currently available information, WHO does not recommend against the use of of ibuprofen.”

There was a letter in the medical journal The Lancet that hypothesized that ibuprofen might make people more vulnerable to infection but they did not offer this as something for which there was evidence.

In the ICU, we avoid ibuprofen in general because in critically ill patients it can lead to kidney injury and stomach ulcers but for mild disease it should be fine for people at home if the acetaminophen is inadequate in easing the symptoms.

Guiafenesin with dextromethorphan (AKA Robitussin DM, Mucinex DM)

This is the nasty tasting cough syrup you remember from your youth. It has minimal side effects and is low risk. Guaifenesin loosens up the mucus while dextromethorphan suppresses the cough sensation . Cough is a major feature of COVID-19 so I highly recommend it. For me this magic elixir is the only reason I have been able to sleep at all, no matter the taste.

Hydroxychloroquine and Chloroquine

This one has more commonly been referred to by the general public as “that malaria drug Trump was talking about” and has been all the buzz. There is reason to believe that these two medications may be beneficial. Chloroquine is a malaria drug used for decades and hydroxychloroquine is more commonly used for autoimmune arthritis. For our purposes, in laboratory studies of coronaviruses grown in culture these drugs seem to interfere with the virus entering into and moving around the cell.

This led to a single study recently in France. It was a non randomized open label trial of 42 patients that tried to see how chloroquine impacted the viral load. Lets unpack these terms.

Research subjects are usually divided randomly into two groups (i.e. randomized). One group is exposed to an intervention like a drug and the other to a placebo. The reason for randomization is that more evenly distributes patients in the two groups so they are matched in as many criteria as possible (e.g. age, gender, level of illness or comorbidities). As an example, if one of the groups was older or sicker or had more comorbidities it could skew the data.

Good quality research trials usually are doubly blind. This means that both the patient and the scientist doesn’t know who gets treatment or placebo. This prevents conscious and subconscious bias about the likely effectiveness of the medication from skewing the results. Imagine a scientist strongly believes that choloroquine is effective. He may view the patients who receive the drug subtly and subconsciously better skewing the outcomes. The opposite of blinded is “open-label” which this trial was.

To sum up. This trial was impressive in that they were able to organize, run, and publish it in such a short time. It provides support for the culture data that maybe these medications work but this is far from certain.

Now we have to do our risk/benefit analysis. The benefits could be huge. This could potentially save lives but we have to temper that enthusiasm by our doubts about whether the research findings are real. They may not be. With that said, these medications have been around for a long time and are safe and well tolerated. Most side effects are only with long term use but do include liver toxicity and bad heart rhythms.

There’s another wrinkle in the analysis. The manufacturers of these medications could not have foreseen all that is going on and have not manufactured enough of the drug for all of the sick people who may need it. Since it has hit the popular media and since President Trump has created a buzz people are going into hoarder mode. They are trying to get the stuff from their dentist, their veterinarian, and probably their corner heroin dealer. This is going to use up the supply treating people for whom the benefit is low. There will then not be enough for the sickest people who really need it. Just as we’re social distancing, washing our hands and isolating to protect the most vulnerable we must reserve the medication for them as well. I think it should be reserved only for hospitals and only given to patients with severe disease where it can truly save lives. Don’t forget about all the poor arthritis patients that won’t be able to get their needed medication.

The Bottom Line

There are other medications that are being studied and discussed. There’s plasma transfusions as well. These are for the people in the hospital and also have little data. If more comes out we can discuss them in more depth. The bottom line is that it takes a long time to develop and test treatments for diseases and this one came on too fast and its too soon. As of now, we are relying on the good practice of critical care medicine to provide supportive care with the hopes that better treatments will come along. As with all viral infections the best hope is an effective vaccine. Maybe the coronavirus will convert a few anti-vaxxers.

Sources:

• https://www.npr.org/sections/health-shots/2020/03/18/818026613/advice-from-france-to-avoid-ibuprofen-for-covid-19-leaves-experts-baffled
• Gautret, P., Lagier, J. C.. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, 105949.