Tuesday, March 24, 2020

Scientists chase two fronts in how to treat coronavirus but 'there's no magic drug right now'

Elizabeth Weise USA TODAY 3/24/2020


SAN FRANCISCO — Doctors and scientists are working furiously to find effective treatments for the illness caused by the new coronavirus but are cautioning the public not to self-medicate or hoard mentioned drugs not yet proven to work.

Despite widespread rumors, social media reports and President Trump's own optimism surrounding the effectiveness of several existing drugs, so far there are no proven treatments for COVID-19, according to the U.S. Centers for Disease Control and Prevention.

“There’s no magic drug out there right now,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said at a news conference on Thursday.

When COVID-19 treatments do arrive, they will likely fall into two categories, say experts. The first will be aimed at slowing down replication of the virus in patients early in the disease. The second will help stop the deadly autoinflammatory response in the lungs in its critical stage.

The drugs touted by the president include the malaria drugs chloroquine and hydroxychloroquine, the experimental antiviral drug remdesivir and azithromycin, a bacterial antibiotic. They remain, however, classed as “investigational therapeutics” because there isn’t enough data to show they are a safe and effective treatment for the illness.

“We often see antiviral therapies (that are promising) in the test tube and animal models. But before we give it to patients with confidence, we really need to see the data in humans,” said Jeffrey Klausner, a professor medicine and public health at the University of California, Los Angeles.

Anecdotal evidence may show when people are given a certain drug their condition improves or stabilizes but other factors could be at play. A person may have gotten better on their own, made it to the hospital more quickly or had fewer underlying risk factors impacting the course of the illness.

“Many drugs have been thrown out as being possibly helpful. But right now, we don’t have a good control of who’s getting it and at what stage," said said Rodney Ho, a professor of pharmaceutics at the University of Washington in Seattle who researches viral diseases and treatments. "We don’t have a complete picture yet.”

Labs and companies worldwide are busy screening likely drug candidates to see if they bind to proteins on the surface of the SARS-CoV-2 virus that causes COVID-19. The problem is, a screen only tells you whether the proteins bind, not the effects, explained Kevan Shokat, a professor of cellular and molecular pharmacy at the University of California, San Francisco.

Proteins can block or activate responses in a cell, so a drug could stop a function the cell uses to protects itself making the patient worse. It could “actually help the virus,” he said.

“There could be drugs that have no benefit, drugs that have a benefit and drugs that do harm,” Shokat said.

No one should expect immediate clarity, said Marc Jenkins, who directs the center for immunology at the University of Minnesota Medical School in Minneapolis.

“Every possible strategy will be tried," he said. "I suspect that’s going to be confusing for a while because there will be so many things being tried."

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Patients with COVID-19 go through a series of stages in their illness. Exact percentages are impossible to know yet but general patterns are beginning to emerge.

For some of those infected, there are few to no symptoms. By far the largest group currently visible to medical professionals are those who present with fever, headaches and cough, and in some cases shortness of breath. Most will get better on their own.

Currently, it appears about 15% of those infected go on to have severe illness and need to be hospitalized. Another 5% become so ill that they must be treated in an intensive care unit.

Antiviral drugs would be used early on in the infection to slow or stop the virus from reproducing in the patient’s body, allowing the immune system to respond, shortening illness duration and halting progression to more severe forms of the disease.

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Such treatments would be similar to antiviral medications given at the onset of the seasonal flu, such as Tamiflu. Available only by prescription, these drugs, taken within two days of becoming sick, can lessen fever and flu symptoms and shorten the length of illness by about a day.

While numerous possible antivirals that might work against the virus have been in the news, none have been tested to ensure they work against the disease or are safe.

These include remdesivir, chloroquine and hydroxychloroquine, a combination of two HIV drugs, lopinavir and ritonavir and a triple combination of lopinavir and ritonavir plus interferon-beta. Favilavir is being tested in China.

Antivirals are often given in combinations to help decrease the chance the virus can survive and mutate into an untreatable form but they take longer to test.

“Combinations take a long time, you have check (the safety of) each drug at different doses in combination with other drugs in different doses,” said Shokat.

Drugs to halt the cascade of illness

COVID-19 patients with severe illness can develop acute respiratory distress syndrome, or ARDS. This extremely serious syndrome isn’t caused by the virus but by the body’s response to it.

The inflammatory response can include the release of chemicals that can trigger fever and low blood pressure. It can also cause small blood vessels in the lung to leak fluid and fill up the alveoli, the tiny air sacs in the lung that process oxygen and bring it into the bloodstream.

“The vast majority of patients who die from COVID-19 are dying from ARDS,” said Michael Matthay, a professor of medicine and expert on the syndrome.

As the COVID-19 pandemic grows researchers are focusing drugs including monoclonal antibodies that bind to molecules that cause or worsen the cascade of symptoms.

Some of the drugs being investigated include Actemra (tocilizumab) and Kevzara (sarilumab) – both used to treat rheumatoid arthritis – and the experimental drug gimsilumab.Others are being investigated.

In the meantime, experts urge people to remain calm and not experiment themselves with unproven drugs that could have side effects worse than the disease itself.

“Every drug has toxicity, it could make you worse or it could make you better," said Shokat. "That’s why drugs take a long time to develop – because we have to make sure."

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