Limited Supply of Chloroquine, Hydroxychloroquine Could Affect COVID-19 Use

April 3, 2020
Samara Rosenfeld

Investigators grapple with the viability of using chloroquine and hydroxychloroquine to stop the spread of COVID-19.

Francesca Romana Spinelli, MD

A limited global supply could prevent antimalarial drugs like chloroquine and hydroxychloroquine from being used to lessen the symptoms of coronavirus disease 2019 (COVID-19), according to a new letter published by a team of Italian investigators.

Francesca Romana Spinelli, MD, and a team of Italy-based investigators looked at previous studies done on the drugs to learn if they were a viable worldwide option.

Because of their in-vitro effect and early clinical trial results, chloroquine and hydroxychloroquine had been proposed for patients with COVID-19-related pneumonia. The drugs were also included in the Chinese guidelines for the management of the virus.

Research by Manli Wang, MD, and investigators showed that at low micromolar concentration, chloroquine potently blocked viral replication of COVID-19 in-vitro. The drug was effective in patients who received a 500 mg/daily dose.

Hydroxychloroquine also showed an anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) effect after it decreased the viral replication in a time and concentration-dependent way.

Both drugs prevented the viral replication at an entry stage.

More than 100 patients have been treated with chloroquine and showed positive results, and a recent study showed that after 6 days, hydroxychloroquine induced a negativity of viral RNA in nasopharyngeal sample.

Additional trials in Europe, which have not yet began recruiting, aim to assess the efficacy of chloroquine and hydroxychloroquine in preventing symptomatic COVID-19 in healthcare workers or individuals at significant risk.

Chloroquine and hydroxychloroquine have been used for autoimmune rheumatic diseases since the 1940s and have been established as safe and well-tolerated for many patients. What’s more, the medications have low incidence of side effects and generally correlates to the weight-adjusted daily dose.

However, there is an ethical issue with using the drugs, because there is not yet hard evidence from trials that chloroquine and hydroxychloroquine can prevent the actual spread of the virus.

“Is it ethical to propose (chloroquine) or (hydroxychloroquine) for preventing the spreading of COVID-19 without any data coming from evidence-based medicine?” Spinelli, from the Department of Internal and Specialized Medicine at Sapienza University of Rome, and colleagues, asked.

The investigators grappled with whether it would be permissible to take a controlled risk in the event of a pandemic.

Regardless, the investigators wondered if it would be reasonable to consider antimalarials as primary prophylaxis in health patients living in the highest risk regions or to use them in those who tested positive and were asymptomatic.

“The advantage of (chloroquine) or (hydroxychloroquine) is that they are safe and inexpensive to administer for a relatively short time, therefore good candidates for mass administration, whenever not contraindicated,” they wrote.

Supportive data from clinical trials could allow the scientific community to move towards pre-emptive use of antimalarials. If that happened and mass prophylaxis was accepted as a worldwide option, it is unclear whether there would be a large enough supply of chloroquine and hydroxychloroquine to support such an approach.

What’s more, the use of the drugs could have extreme impacts for patients with rheumatic diseases.

“A balanced approach that meets the imperatives of the ongoing pandemic, but which also takes account of the needs of patients already taking these drugs is essential,” Iain McInnes, MD, PhD, president of the European League Against Rheumatism, said in a statement.

The letter, “To consider or not antimalarials as a prophylactic intervention in the SARS-CoV-2 (COVID-19) pandemic,” was published online in the Annals of the Rheumatic Diseases.