Update from Dr. David Clark: Remdesivir and a Four-Drug Combo

Written by: David Clark, PhD, chair of the Coalition for Hemophilia B

NOTE: This article is not intended as medical advice. Readers should seek the advice of their own physician. Because information regarding COVID-19 (novel coronavirus) is ever changing, readers are also asked to check for frequent updates.

This COVID-19 update includes, first, some perspectives on children and COVID-19. Then I will discuss remdesivir and newly published research on a four-drug combo that appears to significantly reduce recovery times.

PEDIATRIC MULTISYSTEM INFLAMMATORY SYNDROME (PMIS)

That’s now the name for the Kawasaki disease-like syndrome affecting children that I wrote about in the last update on COVID Symptoms and Inflammation. PMIS is still rare, but we don’t know whether its prevalence might be increasing. They have been seeing a number of cases in New York City, and unfortunately one child has now died. This is mostly still a mystery.

CHILDREN AND SCHOOL 

There has been a lot of controversy about whether to reopen schools and daycare. Fewer children seem to be infected, and the ones that are infected usually have milder cases. A couple of recent studies give us some more information. One study from China suggests that kids are about one-third less likely to become infected from contact with an infected person, compared to adults. However, it also shows that when schools are open, kids have about three times more contacts with others than adults do. That tends to even out the risk.

A study from Germany showed that kids who are infected have virus levels as high as (and sometimes higher than) adults, which presumably makes them just as infectious. This study also found that kids who are infected but have no symptoms have viral loads just as high as symptomatic children and adults. Because children usually have milder disease, the real risk is thought to be for the adults with whom children have contact. Infected kids might pose a risk for adults at school: teachers, staff members, cafeteria workers, bus drivers. They will probably also bring the risk of infection home to the rest of their family. That could be a problem, especially if the family includes older parents or grandparents or others with risk factors.

On the other hand, we know that school is important for children, both educationally and developmentally. This is a difficult question, and the answer is not yet clear.

Kids are about a third less likely to become infected from contact with an infected person, compared to adults. However, when schools are open, kids have about three times more contacts with others than adults do. That tends to even out the risk.

QUADRUPLE ANTIVIRAL THERAPY 

A new study from six hospitals in Hong Kong suggests that a combination of interferon, ribavirin, and an HIV medication that includes both lopinavir and ritonavir may be effective against COVID-19. In a phase II study, patients receiving the drug combo recovered in a median of 5 days after the start of treatment compared to the control group, where recovery took 12 days. The control group received only the lopinavir-ritonavir drug. There were no deaths in the study. The combo also rapidly reduced viral loads, probably reducing the infectiousness of the patients. This could be a significant finding, but it needs more study.

REMDESIVIR 

You have probably heard a lot about this drug over the last week or so. It is not a cure, but it does seem to tone down the infection somewhat. Patients in the recent clinical study recovered in an average of 11 days compared to the other patients who received a placebo (a fake drug) and recovered in an average of 15 days. That is a 31% improvement. (Note that the four-drug combo described above did better. That study was published on May 8, 2020. Both treatments need more research.)

Unfortunately, remdesivir had no statistically significant effect on death rates in the U.S. study. Plus, there is another study from China that showed that remdesivir was no help for severe patients, although by the time that study was being done, there weren’t enough severe patients left in China to get a good evaluation. Both studies found that remdesivir is safe and adequately tolerated (which means that there were some less-than-mild side effects; otherwise they would have been described as well-tolerated).  

While remdesivir is not a cure, it may be a clue. Having identified something that works somewhat, we can study it further. . . .  In that way, researchers can often not only come up with a good drug but also a better understanding of the disease.  

The U.S. Food and Drug Administration (FDA) has now approved remdesivir for emergency use in severe COVID-19 patients, and the drug’s manufacturer, Gilead, is ramping up production. However, there are problems with distribution of the drug. Hospitals that need it can’t get it, and other hospitals that don’t need it have it. The best regimen for dosing the drug and knowing which patients would benefit most from it are also unclear and need more study. (See FDA warning of 6/15/20 on a newly discovered potential drug interaction related to the investigational antiviral drug remdesivir.)

While remdesivir is not a cure, it may be a clue. Now that we have identified something that works somewhat, we can study it to see what it really does—how it affects the virus or the body’s response to the virus. Then we can see if we can develop something similar that might have a better effect.

This is the way that many medications are discovered. Researchers will take a group of compounds that seem to have some effect on a disease. Then they will make a number of slightly modified compounds and test them to see which ones work better or not as well. By looking at how the different variations perform, they can often get clues about how to modify a compound to get an even better response. Their studies also often help them to figure out how the compound does what it does and why that affects the disease. In that way, researchers can often not only come up with a good drug but also a better understanding of the disease.

Take care everyone and be well.