In July, Brian Estevez was in peak health. However, by the end of the first week of August, he had late-night fevers up to 104 degrees Fahrenheit, cold chills, body aches, shortness of breath, slight nausea, a loss of taste and fatigue — all symptoms of COVID-19.
Estevez tested positive for the virus, and within three days, he received a call from Columbus Public Health about participating in a clinical trial at Ohio State that would test to see if injecting synthetic antibodies, proteins that fight off infections in the immune system and protect the body from being infected again, into his system could fight the illness.
“I’m living alone with my two dogs and just going up the stairs would have me winded and so I didn’t know what to expect if things got worse,” Estevez said. “Then what was I going to do if I didn’t have anybody here to, like, know if I can’t breathe, or whatever it may be?”
Estevez is one of thousands around the world participating in clinical studies, with experts racing to test vaccines and treatments to mitigate the further spread and sickness of the coronavirus. Ohio State is no exception, conducting multiple clinical trials addressing various stages of the pandemic.
“We wanted the OSU community, and the larger central Ohio community overall, to have access to these very important studies and we wanted to make sure we also had something to offer for every stage of the COVID-19 disease,” Carlos Malvestutto, an assistant professor in the Division of Infectious Diseases at the Wexner Medical Center at Ohio State, said.
Estevez is participating in the clinical trial for BLAZE-1, a study in its second phase, determining if an antibody called LY-CoV555 can mitigate the spread of the coronavirus within an infected person’s body. In theory, the antibodies dull the spikes on the outside of the virus cell, preventing it from infecting healthy cells, Malvestutto said.
Malvestutto said the spikes on the surface of the coronavirus attach to protein receptors found on many cells, which serve as a gateway for the virus, allowing it to hijack the cells’ machinery and begin replicating.
The synthetic antibody was developed through a collaboration with American pharmaceutical company Eli Lilly and Company and AbCellera Biologics, a Canadian biotechnology company.
Although antibodies are typically produced by the immune system, Malvestutto said the synthetic antibody is created by extracting and cloning the antibodies from recovered COVID-19 patients’ plasma.
Participants must be 18 years or older, exhibit mild to moderate COVID-19 symptoms — such as fever, cough, headache, muscle pain, nausea, shortness of breath when active, sore throat or abdominal pain — not require hospitalization and start the infusion within three days of testing positive for COVID-19, according to the Eli Lilly and Company website.
Malvestutto said after participants are evaluated and cleared for the trial, they receive the hour-long infusion and are monitored for side effects for an additional two hours.
Over the next several weeks, Malvestutto said a team of research nurses follow up with participants like Estevez through home visits to monitor their progress and to see if the patients are recovering more rapidly.
“It’s been pretty great, especially since it’s done here at my house. I don’t have to go anywhere, they have made it very convenient,” Estevez said. “Also, just them looking out for other people, so that if I have the potential of getting anybody infected, that’s reduced.”
The Ohio State Wexner Medical Center will also be serving as a test site for a 30,000-person, multicenter clinical trial testing an experimental COVID-19 vaccine. The medical center will host about 500 participants, including college students.
The vaccine, called AZD1222, was co-developed by the University of Oxford and AstraZeneca, a biopharmaceutical company, and is in its third and final phase. Malvestutto said the trial aims to distribute the vaccine to participants in a matter of two months and will monitor their progress over the following two years.
Malvestutto said the study seeks participants at a higher risk of developing a severe case of COVID-19, such as those age 65 or older, those with existing health conditions and those with jobs requiring direct contact with others, such as in health care facilities, prisons and jails, but also populations disproportionately affected by COVID-19, including people who are Black, Latino and Native American.
“We want to make sure that the clinical trial population that will be part of this study is well-represented by members of those groups, because that’s the only way that we can then also draw adequate conclusions,” Malvestutto said. “The worst thing that can happen in a trial is we just did not have enough participants that were a part of this group to be able to say something meaningful about how well it works in that group.”
Malvestutto said the vaccine will make the cells create coronavirus spike proteins, prompting the immune system to produce antibodies to target and fight off the virus and recognize the virus in any form that it appears later on.
“If the spike protein has antibodies attached to it, it cannot then bond to that receptor on the cells and it cannot attack cells and complete it’s replication cycle,” Malvestutto said.
Malvestutto said participants will receive their first dose of the vaccine, then a second dose a month later. Follow-up visits will also occur after three months, six months, one year and two years have passed, with blood and saliva samples taken during every visit and phone conversations in-between to check in.
Malvestutto said results from earlier phases of the trial showed no serious adverse effects in more than 5,000 people who have received the vaccine so far, with only side effects typically seen with vaccine injections, including mild pain in the injection site, mild fever and headaches.
“We haven’t seen anything serious, but of course we will be paying very close attention to look for any possible side effects, because this vaccine would never be approved if what we see is there are toxicities or other, more serious side effects,” Malvestutto said.
Results from an early-stage clinical trial in the United Kingdom showed the experimental vaccine is safe and prompts a strong immune response, producing both antibodies and T-cells, which locate and attack infected cells, according to an Ohio State press release.
Malvestutto said the ability to run such a large trial is due to the infectious diseases expertise of all the research networks and partners under the COVID-19 Prevention Network.
“Normally, it would take years to do something like this, but in just a few months, everything has been set up to be able to get this going,” Malvestutto said. “So, everything is moving at an unprecedented pace, but it’s all being done carefully and following the same standards that we follow to run all of our clinical trials.”
The AZD1222 trial will begun once it is approved by the Institutional Review Board.
Malvestutto said a new clinical trial, CoVPN3502, will begin after approval by the Institutional Review Board and will evaluate if a cocktail of two neutralizing antibodies will prevent participants already exposed to the coronavirus from contracting COVID-19. The injection is produced by biotechnology company Regeneron Pharmaceuticals.
Malvestutto said this trial is in its third phase and tests if those antibodies will prevent people from acquiring the virus if they live with someone who tested positive for the disease. This preventative measure is known as post-exposure prophylaxis, a treatment to prevent someone exposed to a disease from becoming infected.
“One of the things that we want to know is, ‘If I live with someone who has COVID-19, is there anything that I can take to protect myself so that I don’t get COVID-19?’” Malvestutto said.
Malvestutto said the implementation and follow up for this study is the same as for BLAZE-1, with participants being monitored by phone and at-home visits with research nurses.
Malvestutto said participants of all the clinical trials will receive compensation for the time that they volunteer.
“We are very grateful for clinical trial participants,” Malvestutto said. “If it wasn’t for volunteers, then everything we’ve learned about managing diseases would be impossible.”
Malvestutto said all three clinical trials are randomized, double-blind placebo studies, meaning that participants will be randomly selected to either receive the treatment or a placebo treatment and neither the participant nor the researcher knows which they received until the end of the study. He said this is important because it provides evidence for how safe and effective treatments are to protect those that receive them against the virus, which will continue to spread if there is no vaccine.
“We need an effective vaccine to protect the population so that we can get to the end of the pandemic so that we can immunize a large enough proportion of the population so that the virus will not be able to continue to spread,” Malvestutto said.
Editor’s note: This story was updated Sept. 8 at 3:24 p.m. to include that CoVPN3502 and AZD1222 trials will begun once approved by the Institutional Review Board.
Correction: A previous version of this story named the post-exposure prophylaxis trial as COVPN 3052. The trial name is CoVPN3502, and the story has been changed to reflect this.