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Alleviation Before Cure

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Alleviation Before Cure

With a vaccine a longer way off, scientists are racing to develop effective pharmaceutical treatments for Covid-19. April 23, 2020
Covid-19
Health Care

No proven pharmaceutical agents specific to the treatment or prevention of Covid-19 currently exist. For now, we must rely on nonpharmaceutical interventions—social distancing, hygiene, and closings of schools and businesses—to mitigate the spread of the virus. For severely ill patients, the best we can do at the moment is supportive care, from intravenous fluids, oxygen, and ventilators to dialysis and blood-pressure-support medicine.

As the United States begins to scale back on the most extreme mitigation measures, public-health officials will turn their efforts toward contact tracing. But we still need therapies that can cure early infection and prevent the worsening of asymptomatic or mild disease, and medications that can prevent individuals from becoming infected before (or right after) they are exposed. These pharmaceutical interventions will enhance our “test-and-treat” containment strategy.

We also need therapies for those who have already developed complications from Covid-19. As with other coronaviruses, Covid-19 can directly invade and damage the lungs, causing pneumonia. Severe Covid-19 infection puts the immune system on overdrive, such that it starts to attack the body. As a result, many of the body’s organs stop working simultaneously. Many of the deaths attributed to Covid-19 infection come from this immune-system overdrive, known as a cytokine storm, and its manifestation in the lungs, known as acute respiratory distress syndrome (ARDS).

Another type of therapy under investigation focuses on how the virus infects the body’s cells. Solid evidence shows that the virus grabs hold of the surface of the cell it will infect at a site called the angiotensin-converting enzyme 2 (ACE 2) receptor. It is hoped that, by blocking this receptor or reducing the number of receptors, fewer of the viruses will bind and infect cells—reducing injury to the lungs and rest of the body.

Many of the needed pharmaceuticals are about to start the necessary randomized clinical trials to test whether they work better than our current standard of care. (Information on all registered trials can be found at clinicaltrials.gov.) The types of pharmaceuticals being developed and tested can be divided into several categories: anti-viral medications, immune-enhancing therapies for severe disease, cytokine-storm therapies for severe disease, and ACE2-directed therapies.

The most publicized medications for prevention and treatment of Covid-19 are the anti-malarial drugs chloroquine and hydroxychloroquine, also used to treat rheumatoid arthritis and systemic lupus erythematosus. In response to the outbreak of another coronavirus in 2012, chloroquine was tested and found to block Middle East respiratory syndrome (MERS) coronavirus from infecting cells. Multiple clinical trials are testing whether chloroquine, either by itself or combined with other medications such as azithromycin (an antibiotic), can be used for pre- or post-exposure prophylaxis, asymptomatic and mild disease, or even moderate-to-severe disease. While limited studies from France and China have suggested that chloroquine might be effective in treating severe disease, preliminary results of well-designed clinical trials have revealed safety concerns. Whether chloroquine can be used safely, and in which instances it is effective, depends on results from clinical trials occurring around the world.

Anti-viral pharmaceuticals disrupt the ability of the virus to replicate. The highest-profile medication in this class is remdesivir. A report in the New England Journal of Medicine on the use of remdesivir in hospitalized patients with severe Covid-19 showed hopeful results. Here, too, as with all the other anti-virals being tested—including lopinavir/retonovir, ribavirin, umifenovir, and favipiravir—the results of clinical trials are needed before we can draw any conclusions.

The most intuitively compelling therapy for patients with severe disease is the use of plasma (the fluid part of blood) from recovering Covid-19 patients to treat severely ill patients. It’s believed that this “convalescent plasma” has virus-fighting antibodies that will enhance a sick patient’s ability to fight off the infection. Other drugs known to increase the immune response in severely ill patients are also being tested.

Therapies being tested among severely ill patients include genetically engineered antibodies that block the cytokine signals that cause cytokine storms. Therapies that might throttle out-of-control immune responses, such as corticosteroids, are being tested in severely ill patients. And trials examining the effect of common blood-pressure medications are also being conducted, on the hypothesis that certain drugs of this kind (ACE2-directed therapies) can stop the virus from infecting cells.

To date, none of the medications currently being tested have been proven definitively to work, though there have been encouraging signals. When we have proven pharmaceuticals that can prevent and treat mild disease, our “test-and-treat” approach to containment will be ready for application. Effective pharmaceuticals will be essential in reducing the complications and deaths associated with Covid-19 until the development of a vaccine.

Photo by Pedro Vilela/Getty Images

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