Campus plays ‘central role’ in developing antiviral medications and working to attenuate the inflammatory response
As the COVID-19 pandemic wears on, the good news is that Colorado hospitals have moved through the surge of cases they were experiencing from late April to early May. For example, at UCHealth University of Colorado Hospital, the census of COVID-19 patients is down nearly 70 percent from its peak.
However, there are still plenty of individuals with COVID-19 who are in need of effective and safe treatments. Moreover, public health experts anticipate a new surge of patients in late summer or early fall if high levels of social distancing are not maintained.
“The University of Colorado is playing a central role in finding treatments for COVID-19. Together with specialists in infectious disease, emergency medicine, hospital medicine and the critical care community, we are working in partnerships to test these treatments,” says Adit Ginde, MD, professor of emergency medicine in the CU School of Medicine who is also leading several COVID-19 clinical trials.
In just a few months, physicians have developed key findings through multiple clinical trials at CU Anschutz, testing previously FDA-approved drugs and new medications to battle COVID-19.
“Two months ago I would not have guessed we’d have encouraging results so quickly,” says Tom Campbell, MD, professor of infectious disease at the School of Medicine, who is leading many of the trials. “It makes it all the more exciting for those of us who are helping out with the effort.”
Campbell describes two strategies to treat COVID-19: target the virus with antiviral medications, and try to attenuate the inflammatory response. Clinical trials at CU Anschutz use both strategies, and sometimes use them together in the same study.
“The remdesivir trials sponsored by the National Institute of Allergy and Infectious Disease (NIAID) demonstrate that using a medicine that targets the virus directly is effective. So that strategy of using an antiviral approach is validated,” Dr. Campbell says. He has been leading two trials of remdesivir at UCHealth University of Colorado Hospital.
In fact, one trial was so effective in improving time to recovery for patients with severe disease that the NIAID decided to stop the trial and make remdesivir available to those who would benefit. The result is that doctors now have a means to treat COVID-19. It does not mean it is a cure or that better drugs won’t be developed. But at least it is one tool.
In addition to remdesivir validating the antiviral strategy, Dr. Campbell says the use of convalescent plasma falls in the same category. At UCHealth, David Beckham, MD, is leading a clinical trial to distribute COVID-19 convalescent plasma to regional hospitals to treat patients that are in the hospital with COVID-19. “Convalescent plasma, or plasma from patients that have recovered from COVID-19, may contain antibodies that can help fight COVID-19 in sick patients in the hospital,” says Dr. Beckham, associate professor of infectious disease in the School of Medicine.
Just last month, Dr. Beckham received a COVID-19 research pilot grant from the CCTSI. “The grant will help get the system started, develop the databases to study what happens to the patients after treatment and help provide initial support to develop antibody tests,” Dr. Beckham says.
The drug that has received by far the most press coverage-both positive and negative-is hydroxychloroquine. Dr. Ginde is leading several clinical trials that involve the drug. He explains that the drug’s primary effect is antiviral, but there are some lab data that suggest it also works to modulate the immune response.
“It is probably the reason why it would have potential to work in more advanced illness,” Dr. Ginde says. The drug is being tested in clinical trials across the spectrum of illness for prevention, outpatient and inpatient treatment.
Dr. Ginde is co-leading a blinded placebo-controlled study with Marc Moss, MD, professor of pulmonary and critical care medicine in the School of Medicine, on the effectiveness of hydroxychloroquine in hospitalized patients. Because the study is blinded, there are no early results, but nearly 400 patients nationally have been enrolled, including 33 in Colorado. Ginde is the national lead investigator for another blinded placebo-controlled study of hydroxychloroquine vs. another antiviral called lopinavir/ritonavir, which is an older antiretroviral agent used to treat HIV. The trial involves outpatients with COVID-19 and the goal is to prevent hospitalization.
“Antiviral agents may be most effective when given in the earliest stages of disease. You want to stop it [the virus] early before the patient’s immune response starts a dangerous spiral of damage.”
Strategies to modulate the inflammatory response
Some people who get very ill with COVID-19 have a very exaggerated hyper-inflammatory response even after the virus is no longer a threat. The body continues to release cytokines, which may attack multiple organs including the lungs and liver. This suggests that the problems some patients experience in terms of respiratory failure may be driven by the body’s response against the virus.
One of the drugs in this category that doctors have been testing is sarilumab, which had already been FDA approved to treat rheumatoid arthritis. Dr. Campbell has been leading a sarilumab clinical trial and early data from the trial show it did not provide benefit in people with milder version of the disease. “Going forward, we are only enrolling people [in the sarilumab trial] with critical illness and who require ICU admission and ventilation,” Dr. Campbell says.
A new study that employs the strategy of calming the body’s hyper-inflammatory response features another FDA-approved drug to treat rheumatoid arthritis: baricitinib. The Adaptive COVID-19 Treatment Trial 2 (ACTT 2) is sponsored by the NIAID and will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone in hospitalized patients. It has just launched at the Rocky Mountain Regional Veteran Affairs Medical Center and other sites across the United States.
Down the road, the next wave of COVID-19 clinical trials will almost certainly involve monoclonal antibodies to attack the coronavirus spike protein. Dr. Beckham says he hopes his work now will inform the next developmental steps to creating monoclonal antibody therapies and even vaccine approaches to treat or prevent SARS-CoV2.
Dr. Ginde says, “We are using the experience in this wave of illness, trying to learn what we can about treatment and getting ready for future waves.”
Guest contributor: Wendy S. Meyer, Colorado Clinical Translational Sciences Institute