The response of the research enterprise to COVID-19 has been agile and multi-faceted. With more than 50 active or completed IRB-approved studies plus basic and preclinical projects, Wake Forest School of Medicine is leading the regional response and actively participating in national and global COVID-19 efforts. Broadly defined, these projects can be grouped into the following categories:
- Therapeutic Trials
- Protecting Health Care Workers
- Community-focused Projects
- Disease Characteristics and Treatment Trends
- Predictors of COVID-19 in Cohorts
If you are interested in participating in clinical trials with Wake Forest Baptist Health, visit our Be Involved page to learn more about what opportunities currently exist. This list of summaries and publications is not comprehensive and represents a portion of Wake Forest's research on COVID-19.
Research Study Summaries
These studies will enhance our knowledge base of the susceptibility, treatment and prevention of COVID-19 in the communities we serve and beyond. This page will be regularly updated with additional projects.Therapeutic Trials
Leading or participating in emerging treatments so that we offer patients the very best options.
Principal Investigator: John Walton Sanders III, MD, MPH
The biomedical research community worldwide is racing against time to develop a safe and effective COVID vaccine, and Wake Forest School of Medicine scientists are on the front lines of those efforts.
One of the initiatives is the Moderna vaccine trial, a Phase 3 investigation to determine the safety, efficacy and immunogenicity of mRNA-1273, a vaccine that has been developed to prevent COVID-19, the disease resulting from SARS-CoV-2 infection. Volunteers will be followed for up to two years as part of a longer-term vaccine safety evaluation, regardless of whether they received the vaccine or the placebo.
Wake Forest Baptist Health is one of 100 sites across the country participating in the study, which has enrolled a total of 30,000 volunteers. John W. Sanders, MD, MPH, is principal investigator of the local site, which has recruited its full target of 300 participants. Sanders is chief of infectious diseases at Wake Forest Baptist and professor, infectious diseases, at Wake Forest School of Medicine. He is pleased with the progress so far. “It’s going really well,” he says. “The volunteers have been great, not only giving of their time, but following up appropriately and being really civic-minded, putting themselves into this volunteer situation to try to help us figure out whether or not this [vaccine] works.”
Volunteers are given two injections—one initial shot followed by a second injection one month later. The Moderna vaccine is the first to employ messenger RNA, a genetic code that tells cells how to make protein, instead of a weakened or inactive form of the virus itself. The mRNA is designed to help the immune system generate antibodies so that in case of infection, the virus does not cause illness.
Sanders says it is important for Wake Forest to contribute to the data being collected nationally, and that it is an honor for the Triad and western North Carolina to be represented in the national demographic.
Principal Investigator: Caryn Gee Morse, MD, MPH
Co-morbidities such as diabetes, hypertension, heart disease and kidney disease are known to put COVID-19 patients at increased risk of serious complications, including death.
The DARE-19 study is investigating the use of an FDA-approved diabetes drug, dapagliflozin, in people with COVID-19 who are hospitalized but not on mechanical ventilation. The drug has previously been shown to have potent heart- and kidney-protective effects in patients with type 2 diabetes, heart failure and/or chronic kidney disease, and may afford protection of those vital organ systems in the setting of COVID-19.
“This study is looking at this drug as an adjunct to other interventions, to try to prevent people who are already pretty sick from getting sicker,” says Caryn Gee Morse, MD, MPH, an associate professor of infectious diseases at the Wake Forest School of Medicine, who is participating in the international, multicenter, parallel-group, randomized, double-blind, placebo-controlled study in hospitalized, adult COVID-19 patients at Wake Forest Baptist Health. The trial will enroll up to 900 patients worldwide, and is led by the St. Luke’s Health System from Kansas City.
“The drug probably has some benefits that we don’t really understand, not just for COVID but for other at-risk, critically ill patients.”
If it turns out that the drug is safe and effective as an adjunct to COVID-19 therapies to help reduce end organ damage, the hope is that it can also be investigated for use in other overwhelming infectious conditions, and possibly even in non-infectious sepsis. Right now steroids are used to reduce inflammation, but “the idea of using something that more directly protects organs from the ups and downs of blood pressure and inflammation as well as direct viral attack is pretty interesting, and, I think, unique,” Morse speculates.
Principal Investigators: Daniel Clark Files, MD, and Karl Williams Thomas, MD
One of the urgent issues associated with COVID-19 treatment strategies is determining whether drugs already approved for other uses as well as entirely new medications can effectively treat COVID-19 in critically ill patients.
The I-SPY trial is intended to address that question. It uses an “adaptive platform trial design” so that several possible drug treatments can be tested at the same time. With this type of design, study participants are randomly allocated one of 4 or 5 treatment “arms” with each group receiving a different therapeutic. Those drugs found to be most promising potentially move forward for further testing, while those found to be least promising are removed from the study.
Several drugs have been identified that either neutralize the virus or help heal lung or other organ injuries that make people severely ill from coronavirus. All study volunteers also receive medications such as remdesivir that are approved as standard of care for the virus.
Wake Forest Baptist Health is the first health system in the country to enroll patients in this Phase 2 clinical trial.
“The adaptive design of this trial allows us to constantly analyze the data and learn which drugs are working and which ones are not,” says Daniel Clark Files, MD, co-principal investigator for the Wake Forest Baptist site and associate professor of pulmonary, critical care, allergy, and immunologic diseases for Wake Forest School of Medicine.
I-SPY stands for “Investigation of Serial Studies to Predict Your COVID Therapeutic Response with Biomarker Integration and Adaptive Learning.” The study is a collaboration among pharmaceutical industry members of the COVID Research & Development Alliance, the Quantum Leap Healthcare Collaborative, and the U.S. Food and Drug Administration.
“By identifying effective treatments in real time, the goal of the study is to reduce mortality and the length of time patients spend on ventilators,” says co-principal investigator Karl William Thomas, MD, professor of pulmonary, critical care, allergy, and immunologic diseases for Wake Forest School of Medicine.
Hydroxychloroquine (HCQ) has been widely discussed as a potential therapeutic for COVID-19. But further research is necessary to validate or refute current findings on the therapy and is a priority for researchers of the Prevention and Early Treatment of Lung Injury (PETAL) Network, a group of 12 centers comprised of 50 hospitals funded by the NIH-NHLBI and dedicated to preventing and treating acute lung injury. Wake Forest School of Medicine leads the Southeast Clinical Center for the PETAL network.
Clark Files, MD, associate professor in Pulmonary, Critical Care, Allergy and Immunologic Medicine, and Chadwick Miller, MD, professor in Emergency Medicine, are participating in PETAL’s multicenter trial called ORCHID—a double blind placebo-controlled randomized clinical trial (RCT) of oral doses of HCQ by offering the option to join the study to individuals hospitalized at Wake Forest Baptist Health for COVID-19. This RCT methodology is often called the “gold standard” of disease-based studies because it helps deter unconscious bias in addition to testing for safety and efficacy.
HCQ was originally developed to treat malaria and is currently used to treat certain types of rheumatologic conditions. It’s readily available, affordable, has minor side effects and has shown to be effective against the SARS-CoV-2, the virus causing COVID-19, in bench testing.
“If we find that hydroxychlorquine shortens the duration of COVID-19 or prevents very severe disease, the drug will be immediately available for patients. If we find that it does not help patients, or has significant side effects, we will also help patients by not exposing them to this drug as part of routine care for COVID-19 outside of a clinical trial,” says Files.
Principal Investigator: Kevin Ward Gibbs, MD
Severe COVID-19 pneumonia results in uncontrolled inflammation that damages the lung, known as acute lung injury.
Regulatory T cells (TREGs) are a type of human cell that suppresses inflammation. To promote lung healing, the RESOLVE trial is administering “off-the-shelf” TREGs derived from cryopreserved human cord blood. The concept is to see if giving people TREGs aids survival in the sickest COVID-19 patients who require life support. It is the first time TREG cell therapy has been studied in either lung injury or COVID.
The study was designed by physicians at John Hopkins and Cellenkos, Inc., the producers of TREG products, and is being implemented by a number of top-tier institutions.
Kevin Ward Gibbs, MD, an assistant professor of pulmonary, critical care, allergy and immunologic diseases for Wake Forest School of Medicine, is principal investigator for RESOLVE at Wake Forest Baptist Health. He brings a background in basic science research on regulatory T cell function, and so is quite familiar with the approach used in the study. “This trial represents a state-of-the-art, cutting edge therapeutic option for patients with COVID,” he says. Wake Forest is one of several sites collaborating on RESOLVE.
According to Gibbs, if TREGs improve outcomes for patients with severe COVID, the study may provide an immediate benefit for the sickest patients during the pandemic. “In the long term, a successful cell-based therapy would be a clinical first for patients with severe pneumonia and lung injury, and could potentially change how we manage the disease,” he notes.
Principal Investigator: Caryn Gee Morse, MD, MPH
In collaboration with scientists at the University of North Carolina at Chapel Hill and biotechnology company Ridgeback Biotherapeutics, Caryn Gee Morse, MD, MPH, an associate professor of infectious diseases at the Wake Forest School of Medicine, is the site principal investigator for two clinical trials of EIDD-2801 (molnupiravir) at Wake Forest Baptist Health, one trial for outpatients and one for inpatients.
Outpatient Study
For people infected with COVID-19, one of the treatment challenges is to intervene early enough in the disease course to prevent them from requiring hospitalization.
EIDD-2801 is a novel anti-viral drug designed to stop the infection early. In the study, EIDD-2801 is administered within seven days of the onset of symptoms. “We hope to stop the infection from progressing to the point where people need to be hospitalized,” says Morse.
The drug has a unique mechanism of action. Its most important characteristic is that it is delivered in pill form. Morse says that many of the therapeutics currently being studied require an IV preparation and administration in the hospital setting.
She expects important science to emerge from the study. Patient participants taking the drug or a placebo are required to visit the clinic four times in the first week of symptoms for a nasal swab. Those swabs should yield significant data on the relationship between viral kinetics and COVID-19 and help better understand the drug’s impact on disease progression. “We hope to have some very specific data about how the anti-viral medication curtails the viral replication,” says Morse.
The Phase IIa, double-blind, placebo-controlled, randomized, multicenter study has an initial enrollment of 60 participants at all sites, which will expand to a larger study if everything goes well. Dosing is still being evaluated, beginning at 200mg twice daily.
Inpatient Study
Morse is also involved with a clinical trial of molnupiravir in COVID-19 patients who are sick enough to require hospitalization.
The study is similar in design to the outpatient protocol, but in this case the oral formulation is given to people in the hospital. By treating inpatients, there is more opportunity to look in more detail at the way the drug is metabolized, with frequent blood draws.
“From previous respiratory viruses we know that if we can treat people earlier, they tend to not develop any significant illnesses. That’s the data generally from anti-virals that work against other viruses like the flu,” says Morse. The researchers speculate that COVID may well react similarly.
She notes that currently remdesivir is the standard of care for most people sick enough to be hospitalized, but recently published data suggest that it may not have much impact on mortality. The EIDD-2801 protocol incorporates both patients being treated with remdesivir and those not receiving remdesivir, to see if there is any difference in outcomes with the two groups.
“We’re still seeking effective treatments that act against the virus in really sick people,” Morse observes. The goal of this study is to help remedy that problem.
Principal Investigator: Caryn Gee Morse, MD, MPH
COVID-19 is known to cause numerous, serious, and often unpredictable complications, particularly in the upper respiratory tract.
In an effort to identify an effective treatment to prevent respiratory difficulties in COVID-19 patients, Caryn Gee Morse, MD, MPH, an associate professor of infectious diseases at the Wake Forest School of Medicine, is conducting a clinical trial involving an FDA-approved inhaled corticosteroid called ciclesonide, or Alvesco, at Wake Forest Baptist Health.
Early in the epidemic, evidence emerged that exuberant (i.e., overly aggressive) inflammation causes many of the serious complications of COVID, including lung injury. “We wanted to look at whether by treating people earlier with an inhaled corticosteroid they would have less symptoms and be less likely to come into the hospital,” say Morse.
She noted that the protocol is “very low-touch,” with minimal contact during the pandemic. That fact is one reason she agreed to participate in the multi-center, randomized, double-blind, placebo-controlled trial. Symptomatic participants are randomized to receive placebo or the inhaled corticosteroid inhaler, and then they are sent home with a pulse oximeter and a smart phone app for tracking symptoms. They record their symptoms, the study team checks in frequently with each participant by phone, and participants return in 30 days for assessments and antibody testing.
“The treatment seems to be well tolerated, and of course the hope is to have something to give people to improve symptoms and reduce hospitalizations,” says Morse.