SARS-CoV-2, the virus that causes COVID-19, continues to spread, leading to more than 26,000 deaths worldwide in less than four months. Efforts are progressing to develop a coronavirus vaccine, but it's still likely 12 to 18 months away.
In the meantime, the pandemic, with more than 500,000 confirmed cases worldwide, is driving researchers to find safe and effective therapies for patients with COVID-19, and an antimalarial drug is potentially on the front lines of that effort. While new and repurposed drugs are being tested in clinical trials, some of these promising drugs are simultaneously being used off-label for compassionate use to treat patients.
Some of the medications being used to treat COVID-19 are known to cause drug-induced prolongation of the QTc in some people. The QTc is an indicator of the health of the heart's electrical recharging system. Patients with a dangerously prolonged QTc are at increased risk for potentially life-threatening ventricular rhythm abnormalities that can culminate in sudden cardiac death.
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Neutralizing that threat means identifying patients who are most susceptible, and knowing how to safely use these medications.
A study published in Mayo Clinic Proceedings details more information about potential dangers and the application of QTc monitoring to guide treatment when using drugs that can cause heart rhythm changes.
WHAT'S THE IMPACT
Hydroxychloroquine is a long-standing preventive and treatment drug for malaria. It also is used to manage and minimize symptoms of inflammatory immune diseases, such as lupus and rheumatoid arthritis.
In laboratory tests, hydroxychloroquine can prevent the SARS-CoV and SARS-CoV-2 viruses from attaching to and entering cells. If these antiviral abilities work the same way in animals and humans, the drug could be used to treat patients and limit the number of COVID-19 deaths.
On a cellular level, potential QT-prolonging medications, like hydroxychloroquine, block one of the critical potassium channels that control the heart's electrical recharging system. This interference increases the possibility that the heart's rhythm could degenerate into dangerous erratic heart beats, resulting ultimately in sudden cardiac death.
Accordingly, Mayo Clinic cardiologists and physician-scientists have provided urgent guidance on how to use a 12-lead ECG, telemetry or smartphone-enabled mobile ECG to determine the patient's QTc as a vital sign to identify those patients at increased risk -- and how to ultimately minimize the chance of drug-induced sudden cardiac death.
The antimalarial drugs chloroquine and hydroxychloroquine, as well as the HIV drugs lopinavir and ritonavir, all carry a known or possible risk of drug-induced ventricular arrhythmias and sudden cardiac death. Prior to starting treatment with these medications, it's important to get a baseline ECG to be able to measure changes.
This starting point measurement could be from a standard 12-lead ECG, telemetry or a smartphone-enabled mobile ECG device. On Monday, the Food and Drug Administration granted emergency approval of AliveCor's Kardia 6L mobile ECG device as the only FDA-approved mobile device for QTc monitoring with COVID-19.
The mobile device's ability to remotely provide the patient's heart rhythm and QTc value does not require an extra ECG technician to take the measurement in person, thus saving increased exposure to COVID-19 and the need for more personal protective equipment.
Using the algorithm developed by the Mayo team, the potential risk of drug-induced arrhythmias can be rated and used to modify treatment accordingly. For example, patients with a baseline QTc value greater than or equal to 500 milliseconds, and those that experience an acute QTc reaction with a QTc greater than or equal to 60 milliseconds from baseline after starting treatment with one or more QTc-prolonging drugs, are at greatest risk for drug-induced arrhythmias. Simple QTc countermeasures can be implemented for patients with a cautionary "red light" QTc status if the decision is made to proceed with the intended COVID-19 therapies.
WHAT ELSE YOU SHOULD KNOW
There are a number of considerations around the use of off-label drugs to treat COVID-19. The drugs may or may not be available in large enough supply to treat a worldwide pandemic, even at the current compassionate use stage of testing. It will take careful consideration of COVID-19 patients' circumstances for treating clinicians and patients to decide on the use of drugs or drug combinations that may treat their infection, but which potentially could cause harmful drug-induced side effects.
According to the Mayo team, patients under 40 with mild symptoms and a QTc greater than or equal to 500 milliseconds may choose to avoid treatment altogether, as the arrhythmia risk may far outweigh the risk of developing COVID-19-related acute respiratory distress syndrome.
However, in COVID-19 patients with a QTc greater than or equal to 500 milliseconds, and who have progressively worsening respiratory symptoms or are at greater risk of respiratory complications due to advanced age, immunosuppression or having another high-risk condition, the potential benefit of QTc-prolonging medicines may exceed the arrhythmia risk.
Ultimately, the weighing of risks to benefits depends on whether hydroxychloroquine, with or without azithromycin, is truly an effective treatment against COVID-19, the team said.
THE LARGER TREND
Everything has been in short supply during the coronavirus pandemic, from promising medications to personal protective equipment, and even hospital beds for sick patients. The ongoing situation is causing havoc to healthcare supply chains as global distribution networks are disrupted amid government lockdowns and widespread infection.