COVID-19 Resource Center

COVID-19 Resource Center

Perspective from Brian B. Baggott, MD, FACG
Disclosures: O’Neill reports no relevant financial disclosures.
April 29, 2020
9 min read

New study to provide insight on hydroxychloroquine for COVID-19 prevention in health care workers

Perspective from Brian B. Baggott, MD, FACG
Disclosures: O’Neill reports no relevant financial disclosures.
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William W. O’Neill

The Henry Ford Health System in Detroit recently announced it is leading the WHIP COVID-19 study, which will assess whether hydroxychloroquine will prevent or impede COVID-19 in health care workers and first responders.

Researchers aim to enroll 3,000 volunteers for the randomized, double-blind study, and preliminary results may be ready in as soon as 4 months, according to a press release from the institution. The trial is one of many underway to better understand how to treat COVID-19.

Healio spoke with William W. O’Neill, MD, medical director of the Center for Structural Heart Disease at Henry Ford Hospital in Detroit and one of the organizers of the WHIP COVID-19 study, to learn more.

Question: What is the idea behind the WHIP COVID-19 study?

Answer: We realized late in February that this virus was going to hit America like a thunderbolt. We were really alarmed about the rate of need for ICUs and ventilators that we heard from China and subsequently from Italy. We were bracing for the worst.

William W. O’Neill, MD, medical director of the Center for Structural Heart Disease at Henry Ford Hospital in Detroit and one of the organizers of the WHIP COVID-19 study.

We also recognized that in both Italy and China, up to 15% of patients with COVID-19 were hospital workers. It was apparent that there is a huge risk that hospital workers would become infected.

When we looked at the literature, we saw a note from a publication that about 187 patients with lupus in China who were taking chronic hydroxychloroquine or chloroquine therapy did not get COVID-19. There was a question as to whether or not hydroxychloroquine was effective in preventing COVID-19. The drug has also been used for malaria prophylaxis.

The question then is: Would hydroxychloroquine, given prophylactically, prevent COVID-19 infection? There was no literature and no data on this. We were extremely concerned about the risks of COVID-19 to our health care workers. Unfortunately, that has borne to be true; more than 800 Henry Ford employees have been infected by the novel coronavirus. (Editor’s note: This number was accurate as of the time of publication.) Use of personal protective equipment and other equipment is helpful, but it would be better to find something more definitive for prevention of COVID-19.


About 1,300 health care workers in southeast Michigan have volunteered to participate in the study. (Editor’s Note: This number was accurate at the time of publication.) Our ultimate goal is to enroll 3,000 health care workers and first responders.

We anticipate completing the study in about 3 months. Concerns remain about current epidemic [as well as a recurrence] next fall, so we have to be much better prepared. Let’s hope that there’s a vaccine, but a vaccine for the next flu season is unlikely, so there remains a need to develop therapeutic measures. The hope is that one of these therapies will prove to be effective. That way, we could give it to our health care workers before the anticipated next wave of COVID-19 comes in.

Q: Do you see this therapy eventually moving from a potential treatment for health care workers to one for the general public? How might the success of this trial impact the system of care for COVID-19?

A: This really depends on how positive or neutral the trial is. If it was a home run, then the next thing would be to take a look at high-risk populations. As an example, we know in America, the highest-risk group are people in nursing homes. These people are elderly, sometimes with dementia. The nursing home employees do not have personal protective equipment. There have been pockets of huge rates of infection in nursing homes. The first example was in Everett, Washington, where there was a huge risk for infection and a huge rate of mortality.

The advantage of hydroxychloroquine is that the drug has been around for decades. The risk profile has been very well established for treating malaria and lupus. It has also been used for rheumatoid arthritis. It is an inexpensive, commonly available drug that has a very good risk profile. These things make it attractive as a prophylactic measure for people at high risk for COVID-19 infection.

Q: Are you aware of any cardiac-related adverse effects associated with hydroxychloroquine?

A: If you take a look at the rheumatology literature and the lupus literature, it is very safe. In the instructions for use, there is no consideration for a QT prolongation.

One study in Brazil showed that very high doses of chloroquine, not hydroxychloroquine, may be associated with an increase in arrhythmias. We have scoured the literature, and we really haven’t found any proof that in patients early in the disease, which is probably when it is most effective, that it has any kind of risk.


When patients are in the ICU, they frequently develop myocarditis. With patients who are having myocardial dysfunction, adding the drug may increase the risk for QT prolongation. Those patients are probably not the right ones to treat [with this therapy]. If it works, it is much more likely that the drug is effective very early in the disease course before any myocardial involvement.

It has been very alarming to potential research participants of prophylaxis trials that the FDA issued a warning about using these drugs outside of a trial setting. This implies there is potential risk. The FDA specifically agreed that it was safe to continue the research trials. We had extensive discussions with the FDA about safety of hydroxychloroquine before our Investigational New Drug application was granted. We have not seen any safety concerns in the 350 participants taking medications in our trial. The main safety signal came from an uncontrolled trial of extremely high doses of chloroquine that caused arrythmias in Brazil. This has no bearing on the doses of hydroxychloroquine we are using.

Q: How has the Henry Ford Health System adapted its care of patients who require care from a cardiologist during the COVID-19 epidemic?

A: The virus has a very long lag time. Patients are asymptomatic for many days before developing cough and fever. The illness is difficult to treat in part because people are very infectious before they actually become symptomatic, so community carriers are a real problem.

Once infected, they will start developing severe shortness of breath, then they start getting pulmonary involvement. That is the trigger for admitting them into the hospital. When they come into the emergency room, if they are not hypoxic, they are sent home to quarantine and rehabilitate. If they are hypoxic and they are starting to get pulmonary involvement, they are admitted to the hospital. Then a proportion of those patients — anywhere between 20% and 30% of the patients that are admitted — become so hypoxic with such severe pulmonary involvement that they need to be admitted to ICUs and put on a ventilator. The problem that is so difficult with this disease is that these patients can have a protracted course of ventilation.

At Henry Ford, the average duration of ventilatory support is 10 days right now, so patients linger in ICUs. At peak, we were completely maxed out, and we had to start diverting patients to the University of Michigan. That was only for about a 2- or 3-day period. After that, we have been able to create capacity.


Now we are in a state that we are going to consider a new normal. We believe that we are going to continue to have active COVID-19 infections throughout the summer. As a result, we’re going to have to figure out how to work in that system, perform all of our regular, invasive, elective procedures at the same time that there’s going to be substantial number of patients that are still going to be treated for COVID-19 in the hospital.

Q: How have cardiologists and cardiac surgeons stepped in to help care for patients with COVID-19?

A: We have a 20-bed coronary care unit, and that became a COVID ICU. Our cardiologists and cardiology fellows essentially became experts on COVID-19 infection, ventilatory management and hemodynamic support.

In our institution, very few patients have ended up with cytokine storm or severe myocardial dysfunction. If there is any myocardial dysfunction, it appears to be more right-sided dysfunction because of pulmonary microemboli. At the most severe form of the disease, the patients develop a hypercoagulable state, disseminated intravascular coagulation and then severe left ventricular dysfunction. That is how they die, but that is right at the very terminal portion of the disease. Fortunately, not many patients get to that point.

If the patients are presenting with chest pain, you still have to think about the possibility that they have coronavirus. Now, with more rapid testing, we will be able to rapidly answer the question, so our staff does not get infected by people presenting with atypical presentations of COVID-19.

Q: How has your personal experience been with taking care of patients with COVID-19?

A: This is an insidious disease. Young people survive very easily. They have a high fever, a 2- or 3-day illness and then they are better. Elderly patients have a really difficult time with it. In the early phase, I have empirically treated people with a combination of hydroxychloroquine, azithromycin and zinc. That combination, at least in my hands, has been really effective. I am leaning toward the side of being a believer or an early adopter, but I absolutely agree that randomized trials are going to be required.

I’m not aware of any really good randomized trials of this therapy that Didier Raoult, MD, PhD, from Marseilles, France, has popularized — but his group has treated 900 patients in their hospital with that combination of zinc, azithromycin and hydroxychloroquine with a 0.4% mortality, and have published results of a nonrandomized trial. If they treat patients within 1 week of onset of symptoms, they only have a 1% need of requiring ICU admission. It’s a wonderful, well-done registry, but we need more data. One of my biggest concerns is that at the end of this particular season, we may not have a definitive answer about whether or not that combination works.


Q: What advice would you give cardiologists during this time?

A: The cardiac manifestations of COVID-19 are actually pretty uncommon. Their involvement will primarily be for seeing patients in the hospital who have troponin elevation. Up to 20% of patients with COVID-19 have troponin elevation. Then in the ICU, if you get toward the end of their disease, consideration for hemodynamic support, primarily with right-sided support, might be useful. Once patients get to the point where they have cytokine storm, it’s a lethal prognosis.

Q: What advice would you give researchers during this time?

A: Randomized trials in this setting are incredibly difficult because patients are desperate for a cure, and if anything seems to work, then it gets widely adapted. It is very difficult to do a trial like that. For example, there was never a randomized trial for the drugs to treat pneumococcal pneumonia or tuberculosis. We have to rethink whether or not it is doable to perform a randomized trial in a new disease in a pandemic situation. – by Darlene Dobkowski

For the latest news on COVID-19 including case counts, information about the global public health response and emerging research, please visit the COVID-19 Resource Center on Healio.


Gautret P, et al. Int J Antimicrob Agents. 2020;doi: 10.1016/j.ijantimicag.2020.105949.

For more information:

William W. O’Neill, MD, can be reached at

Disclosure: O’Neill reports no relevant financial disclosures.