What Are the Most Promising Treatments for COVID-19?
With the medical community learning more about COVID-19 (coronavirus) every day, the treatment landscape has changed dramatically since the outbreak began.
When the mysterious illness surfaced in China last December, supportive care was the only option available. Since then, a number of experimental therapies have been rushed into clinical trials for COVID-19 patients. And with medical journals publishing new COVID-19 research studies at breakneck speed, it can be difficult to keep up with the latest news and guidelines.
"Our understanding of potential treatment options is changing rapidly because there has been a tremendous focus in the scientific community on identifying options from a variety of angles," said Jonathan Grein, MD, director of Hospital Epidemiology at Cedars-Sinai. "It's been great to see everybody focused on trying to find therapeutic options that work. But I'd urge the public to be cautious when interpreting headlines about new developments because we need to ensure that the science is sound before recommending anything definitively."
To get a clearer understanding of which treatments are showing promise—both old and new—and how they are being used, the Newsroom spoke with Grein and Jeremy Falk, MD, a pulmonology and critical care medicine specialist and associate director of the Cedars-Sinai Lung Transplant Program, who is treating COVID-19 patients at Cedars-Sinai Medical Center.
Who Is Being Treated?
Patients hospitalized with COVID-19 make up the majority of people who are receiving experimental treatments right now. That's typical when drugs are being tested for newer diseases.
"Patients who are sicker and in the hospital usually have a more advanced illness, and you want to do everything you can to find something that will help them," Grein said. "Hospitalized patients also can be monitored closely for their reaction to a drug."
Many of the therapies being tested for COVID-19 had previously been approved by the Food and Drug Administration (FDA) to treat other diseases, so were easier to test and deploy quickly during the pandemic than were completely new drugs.
This class of medications reduces a virus's ability to make copies of itself. Various antivirals are used to treat influenza, HIV and different types of hepatitis. Several have been tested against SARS-COV-2, the virus that causes COVID-19. So far, remdesivir is the only antiviral treatment that has shown any clinical benefit to patients in a well-controlled trial—a study that includes a comparison (control) group that receives a placebo, another treatment or no treatment at all.
Remdesivir had previously been tested for use against other viruses, such as Ebola. The drug has been evaluated in severely ill COVID-19 patients receiving treatment in an intensive care unit (ICU). Those who received the drug recovered four days sooner on average.
Another medication that acts like an antiviral, hydroxychloroquine, initially looked interesting. This FDA-approved drug is widely available for treating malaria. However, studies have not identified any clear benefit to using hydroxychloroquine for COVID-19, but rather have revealed potential harm to patients. As a result, the FDA revoked its Emergency Use Authorization for COVID-19 treatment June 15.
Several types of drugs that suppress an overactive immune system have shown potential for calming the "cytokine storm," an intense inflammatory response that COVID-19 appears to create in later stages of illness. These drugs have been approved by the FDA for use in patients with inflammatory diseases, such as rheumatoid arthritis, and many cancers. The most studied example, tocilizumab, is called an interleukin-6 (IL-6) inhibitor because of the specific cytokine that it targets.
In clinical trials, tocilizumab has been associated with improved survival rates among seriously ill COVID-19 patients, especially those on ventilators. Further controlled trials are needed to confirm this benefit.
Preliminary data from a study examining the use of another type of anti-inflammatory, a widely available generic steroid called dexamethasone, suggest that this drug might improve survival rates among seriously ill COVID-19 patients. But the study isn't finished, and it's not clear if the treatment causes any serious side effects. Previous attempts to use steroids to treat patients with viral illnesses such as severe acute respiratory syndrome (SARS) have yielded mixed results.
Because steroids and IL-6 inhibitors blunt the immune system’s response, they likely would only be used in the later stages of a COVID-19 illness when the body’s inflammatory response is most damaging. A weakened immune system could potentially make the body more vulnerable to COVID-19.
"We need to be judicious about how and when we use these," Grein said.
Two types of experimental therapies harness antibodies—proteins made by plasma cells in the blood—to treat COVID-19. The body's immune system uses antibodies to neutralize pathogens, such as viruses and bacteria.
One therapy, convalescent plasma, uses antibodies from a recovered COVID-19 patient to treat someone currently infected with the disease. The concept has been used for almost a century to treat many new diseases for which no treatment existed, such as SARS. Many hospitals and biotech companies are recruiting recovered coronavirus patients to donate their plasma to generate this investigational therapy and examine its safety and effectiveness in clinical trials with severely ill patients.
While it sounds simple, the reality is more complicated. Some people don't mount robust immune responses to COVID-19, and the needed antibodies won't be present in their blood. Because the quality of convalescent plasma may vary from person to person, it's not a consistent product. One controlled trial in China showed that convalescent plasma was associated with more frequent and faster improvement in COVID-19 patients, but the study was terminated early due to a lack of eligible patients when the outbreak slowed there.
The second type of therapy isolates the most potent antibodies from a recovered patient and reproduces the antibodies in large volumes to treat COVID-19—possibly preventing people from becoming infected altogether. A number of biotech companies and academic research institutions have developed these so-called monoclonal antibody therapies and are testing them in clinical trials.
"It's similar to convalescent plasma but potentially more powerful and specific," said Falk. "It is essentially providing patients with the antibodies that will someday be made by the body after receiving a COVID vaccination."
Proning To Increase Oxygen Flow
When COVID-19 patients become seriously ill, the disease often attacks their lungs. If they can't breathe well, patients are transferred to the ICU for more intensive treatments. These interventions may include a breathing tube and mechanical ventilator supplying airflow with seven times the volume of oxygen we get from breathing normally.
If that's still not enough, physicians may choose to turn a patient over onto their stomach, which actually is an ideal position to allow the lungs to expand fully. Several nurses and respiratory therapists slowly and methodically rotate the patient to avoid dislodging a breathing tube and to minimize any discomfort for the patient, who is supported by pillows or bolsters while lying in this prone position for about 18 hours a day.
Falk said it's not entirely understood why this helps, but it may involve reducing the pressure that the heart normally applies to the lungs. This pressure compresses a significant amount of lung tissue. When a patient is on a breathing tube, they don't benefit from the lung expansion mechanics our bodies naturally provide. Hospitals have used proning for years to treat patients with severe respiratory issues.
"Humans are not designed to lay on their backs all day," said Falk. "Proning is one of the simplest things you can do to improve survival."
Read more on the Cedars-Sinai Blog: Is it Safe to Travel During the COVID-19 Pandemic?
Experimental COVID-19 Treatments
Investigators at Cedars-Sinai are busy working on various experimental COVID-19 treatments. Read more on the Newsroom about some of these efforts.
- Patients Improve After Immune-Suppressant Treatment: Outcomes for patients who received the drug tocilizumab included reduced inflammation, oxygen requirements, blood pressure support and risk of death, compared with published reports of illness and death associated with severely ill COVID-19 patients.
- Patients Improve After Heart Cell Therapy: Four of six critically ill coronavirus patients significantly improved after receiving an experimental therapeutic designed to reduce inflammation, a major cause of death from this disease, according to a case series published by Cedars-Sinai and Capricor Therapeutics.
- Cedars-Sinai Physician Co-Authors Analysis of Antiviral Drug: In a small group of patients hospitalized with severe complications of COVID-19 and treated with the experimental antiviral drug remdesivir, clinical improvement was observed in 68% of patients treated.