The current toolkit for COVID-19 in adults

People avoided crowds and public events to avoid falling sick. Parents watched their kids nervously for symptoms. In the absence of a vaccine, people turned to therapies, many of them untested, to prevent the disease, treat its symptoms or lessen its severity. With the development of an effective vaccine, the number and severity of cases dropped.

You might be thinking COVID-19, but this description applies equally well to a wave of polio epidemics that plagued the first half of the 20^th century. Polio could lead to muscle paralysis, and those whose lung muscles were paralyzed could not breathe properly. Iron lungs helped patients to breathe. Doctors had patients placed in the sealed chamber, while a set of bellows changed the air pressure, causing their lungs to breathe in and out. Less effective therapies included the administration of serum from recovered polio patients and external and internal use of disinfectants such as hydrogen peroxide.

 

The Salk vaccine—the first vaccine against polio—was licensed in the U.S. in 1955. Others followed. Before the vaccines, polio cases numbered 16,000 per year. Thanks to the vaccines, no case of polio caused by wild poliovirus had originated in the U.S. since 1979 until July of this year, when a case of paralytic polio was confirmed in an unvaccinated adult in Rockland County, New York.

 Vaccines continue to be our best strategy for combating diseases worldwide. For many of those diseases, such as polio, no effective treatments exist.

For other diseases, such as COVID-19, there is a toolkit of treatments, albeit sparse, but vaccination remains the better strategy, said Patrick Flume, M.D., co-director of the South Carolina Clinical & Translational Research (SCTR) Institute and associate vice president of clinical research at MUSC. Flume oversaw many of the COVID-19 vaccine trials at MUSC and served on a committee that decided which COVID treatment trials were the best fit for MUSC and the community.

“Clearly the best approach to managing COVID-19 is through vaccination, said Flume. “Only a couple of drugs have been approved for the treatment of COVID.”

Which therapies worked and which didn’t

Which of the therapies proposed in the early days of the pandemic remain in today’s COVID-19 toolkit and which fell by the wayside?

The National Institutes of Health (NIH) has published guidelines on how to treat COVID-19 in adult patients with healthy immune systems based on the current evidence. These guidelines are updated as new data comes out and gives the greatest weight to data from well-designed randomized controlled trials (RCTs), the gold standard for clinical research. RCTs test therapies head to head or compare outcomes in patients who receive a therapy and those who do not.

“Clearly the best approach to managing COVID-19 is through vaccination. Only a couple of drugs have been approved for the treatment of COVID.”  -- Dr. Patrick Flume

The NIH panel has determined that some medications never worked while others quit working or worked less well as the virus evolved. Others remain effective but are intended only for certain subsets of patients.

Didn’t work

Ivermectin. 

Based on the results of multiple international RCTs that showed that it did not protect against severe disease, the NIH panel recommends against the use of the antiparasitic ivermectin except in clinical trial.

Cell studies had shown that ivermectin could prevent the virus causing COVID-19 from reproducing. However, further studies showed that achieving a similar concentration of ivermectin in human plasma would require a dose that humans could not tolerate, as high as 100 times higher than is currently approved when it is used as an antiparasitic for humans.

“The lesson with ivermectin is panic leads to really bad science,” said Flume. “It could be shown in a laboratory that ivermectin had activity against the virus. But the amount of drug that you would need to give was so high, it was never a real opportunity for a therapy.”

Hydroxychloroquine.

Multiple RCTs have shown that hydroxychloroquine, administered alone or together with the antibiotic azithromycin, does not protect against severe disease in patients who are not hospitalized. For hospitalized patients, the UK RECOVERY trial showed no difference in survival at 28 days and necessitated a longer hospital stay for those receiving hydroxychloroquine compared with those receiving usual care. Patients who were not on ventilators before taking the drug were more likely to require ventilators or die during hospitalization. Hydroxychloroquine has also been linked to serious heart rhythm problems and other side effects in some patients.

Based on this and other clinical trial data showing it not to be effective and to have worrisome side effects, its emergency use authorization, issued on March 28, 2020, was withdrawn on June 15, 2020.

Worked less well as the virus evolved

Monoclonal antibodies.

 

Against the original virus and the Delta variant, “the monoclonal antibodies approach worked well,” said Flume, whose team ran the trials led by Eric Meissner, M.D., Ph.D., which showed the efficacy and safety of monoclonal antibodies produced by Regeneron. However, many monoclonal antibodies, including those produced by Regeneron, quit working or worked less well against Omicron strains. The monoclonal antibody bebtelovimab remained active against many of the circulating Omicron variants but does not work against the new subvariants BQ.1 and BQ.1.1 and should not be used when they are the dominant variants in a region.

Regeneron has developed new monoclonal antibodies that could be effective against Omicron, and Flume is interested in opening a trial at MUSC into its use in patients with compromised immune systems, such as cancer patients undergoing chemotherapy.

“Our approach at vetting these trials is we’re willing to pursue a trial if it's going to make a difference for a population of patients,” said Flume. “From what I’ve heard from our infectious disease and cancer doctors, this is a group that has been badly affected. That’s why we're pursuing that study.”

Remain effective in subsets of patients

Paxlovid.

In most patients with COVID-19 who are not hospitalized and not receiving oxygen, treating the symptoms with over-the-counter medications is enough. However, for those at high risk of severe disease, the NIH panel recommends Paxlovid. Some patients taking Paxlovid may experience a second onset of symptoms after initial symptoms resolve.

Remdesivir.

Remdesivir remains the only antiviral approved for the treatment of COVID-19 in both patients who are hospitalized and those who are not. The NIH panel recommends it as their second choice, after Paxlovid, for nonhospitalized patients at high risk of developing severe disease and their first choice for hospitalized patients not receiving oxygen who are at high risk of developing severe disease. The panel recommends it, along with the steroid dexamethasone, for hospitalized patients receiving conventional oxygen.

Steroids.

Because safety and efficacy data are currently lacking, the NIH panel recommends against steroids such as dexamethasone in patients not receiving supplemental oxygen, whether hospitalized or not. In the UK RECOVERY trial, the use of dexamethasone did not affect survival rates among hospitalized patients who did not require supplemental oxygen.

However, the NIH panel recommends dexamethasone, together with remdesivir, for most hospitalized patients receiving conventional oxygen and, together with one of two drugs used to treat rheumatoid arthritis – baricitinib and tocilizumab – for patients on a respirator. The RECOVERY trial showed that steroid treatments increased survival in patients requiring conventional oxygen or mechanical ventilation.

Misinformation about vaccines threatens to undermine our best protection against viruses

As is true for other diseases brought under control by vaccines, the number of effective treatment options for COVID-19 is relatively low. That’s why Flume believes it’s all the more important for people to be vaccinated against COVID and to boost those vaccines to be sure they remain effective as variants arise. Bivalent boosters, shots that are effective not just against the original strain but also against Omicron, are currently approved for anyone over the age of 5 or 6, depending on the brand.

“As I tell my patients when they ask me in the clinic about whether they should get the booster, my answer to them is ‘I got it,’” said Flume.

“Because some are choosing not to have their children vaccinated, you are beginning to hear about cases of polio in America and measles outbreaks. People today who are having kids have no memory of how bad it was. And we don’t have therapies to treat those viruses, and so vaccination is the single most effective strategy.”

-- Dr. Patrick Flume

Unfortunately, misinformation on social media about the COVID-19 vaccines has hurt vaccination and booster rates and led to a growing distrust about vaccination in general. (See infographic below for Flume’s tips on how to recognize bad science.) The consequences are real, said Flume.

“Because some are choosing not to have their children vaccinated, you are beginning to hear about cases of polio in America and measles outbreaks,” said Flume. “People today who are having kids have no memory of how bad it was. And we don’t have therapies to treat those viruses, and so vaccination is the single most effective strategy.”

Infographic by Danielle Hutchison of SCTR Institute.