USC-VHH Obtains Drug OK’d for COVID-19 Cases

Dr. Armand Dorian and Dr. Heinz-Josef Lenz

As the global battle against the coronavirus persists, doctors at USC Verdugo Hills Hospital have been able to join select others nationwide in deploying what can hopefully be a key weapon in curtailing the deadly virus.
After clinical trials, government officials recently made the drug remdesivir available to hospitals for emergency use on COVID-19 inpatients who meet specific criteria. Though initially developed by the pharmaceutical company Gilead as a hepatitis C treatment (for which it was unsuccessful), the drug was later tested for use against the Ebola virus, SARS and also MERS — the latter two of which are also infections from coronaviruses.
“We were one of the hospitals that did get it and we have already started the process of giving [it to] the patients who qualify for it,” explained Dr. Armand Dorian, chief medical officer at USC-VHH, in an interview this week. “We have now given it to six patients here who have so far improved, so we’re happy with the results we’re seeing.”
Although remdesivir is not the vaccine the world is waiting for as the pandemic’s death toll rises, Dorian said the drug may nevertheless prove useful in certain stages of infection by the virus.
“When you’re in the middle of a pandemic, everyone’s looking for different ways to see if what we have can be of some benefit,” Dorian said. “They’re more adjuncts that buy you time until you get a vaccine or develop a specific medication to fight the illness.”
Though the disease is similar to the flu in symptoms and mortality, the true threat of the new coronavirus is that we as a species are not prepared to naturally fend it off because we’ve never experienced it, and it also is proving to be more contagious than other similar viruses.
“This one, you don’t have any pre-existing antibodies to fight it, not even a similar character to it,” Dorian added.
Ideally, Dorian said, drugs would be administered in a more clinical fashion to facilitate the best research data; sometimes, he said, a researcher will see any change in condition as being a result of medication.
The urgency of the pandemic complicates things, obviously.
“Whenever you give a medication, you get into bias,” Dorian said. “You’re hoping the medication will work, so any improvement you see, you want it to be because of the medicine. The gold-standard studies are double-blinded and placebo controlled. You don’t want the patient to know which medication they’re getting, and you don’t want the person giving the medication to know what medication they’re giving. That way, you don’t introduce bias into the study.”
Meanwhile, Dr. Heinz-Josef Lenz, associate director of clinical science at the Norris Cancer Center at Keck Medicine of USC, also is foraying into the testing of a potential medication against COVID-19. Artificial intelligence has played a key role in identifying baricitinib, a drug used to treat rheumatoid arthritis, as a possible treatment against the coronavirus when used alongside other antiviral medication.
“We knew that this drug has the potential to interfere with the entry of the virus into the cell and prevent the immune response to the virus entry, which causes a lot of damage to the body,” Lenz said, referring to what is called a cytokine storm. “When they looked at the different steps of the virus entry and simulation of the cytokine storm, they looked at what receptors are involved and what drugs can inhibit these particular steps. This drug came up as one of the more potent factors in preventing entry and this immune response.”
In other words, Lenz said, the manner in which this drug suppresses the autoimmune system response that causes rheumatoid arthritis is similar to what appears to be the way to block the virus from triggering an immune system response. The receptors that trigger the body’s immune response to the virus are located in the heart, kidneys and blood vessels, and the resulting inflammation often precedes intubation and ventilator use; reducing the cytokine storm — and thus the inflammation — can theoretically slow the progress of the disease and preclude the need for a ventilator at all.
“When the cells try to defend it, it creates a cytokine storm that actually damages organs, which is why we see problems with breathing, blood clots, heart attacks and kidney failure, depending on the extent of damage,” Lenz explained.
To hear the doctors tell it, “any little news is good news” during desperation mode. Though neither drug will replace the hoped-for vaccine, it’s still useful to know when each one might be more useful in certain phases of infection.
“There are different phases of the illness in which different medications are used,” Dorian said. “The ideal would be to get a vaccine so you don’t go through all of these phases.”
Dorian added that Los Angeles County successfully averted a large surge of patients early in the pandemic through its Safer at Home orders that largely shut down public life and urged people to remain home as much as possible. In the meantime, medical centers had time to prepare facilities to take more critical patients and public testing sites for the disease have since appeared.
“We averted that surge by staying at home, so we’re spreading out people getting ill over a long period of time versus everybody getting sick in a four- to five-week period. Now we’re playing a long game,” he said, later using California-centric terminology to make his point. “Now that we know that the earthquake has not happened, we have time to prepare for the potential earthquake that may come. Instead of it being a tsunami, it’s now a rising tide.”
Lenz said he hopes to make baricitinib available to patients not just at USC-VHH but countywide; the irony of hospitals largely having averted housing a large number of critical patients is that there is a smaller patient pool for the testing.
The revelation about baricitinib, he added, represents one of the more curious and exciting parts of medicine.
“Sometimes drugs have an off-target mechanism and that can be very helpful,” he pointed out. “I think that’s a very nice example for that.”

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