Columbia Scientists Seek New COVID Therapies and Tests
Columbia University researchers have been pursuing several areas of investigation, from monoclonal antibodies to ultraviolet light, and making progress with new ways to detect the virus, prevent transmission, and treat patients with COVID.
CUIMC News asked several investigators to update us on their progress.
Monoclonal Antibodies in Development
Soon after the pandemic began, David Ho’s laboratory started looking for COVID-19 patients who produce especially powerful antibodies that can neutralize the SARS-CoV-2 virus.
Such antibodies, once found in patients, can be produced in large quantities by pharmaceutical companies to treat patients, especially early in the course of infection or to prevent infection in the elderly and other vulnerable groups. Antibodies from Eli Lilly have been approved by the FDA recently, and antibodies from Regeneron (used to treat President Trump) may be next.
Ho’s lab has isolated a diverse variety of neutralizing antibodies [as reported in July in the journal Nature], and two of them have been licensed to commercial partners for clinical development as potential therapeutic and/or prophylactic products. Two other neutralizing antibodies are being developed internally with funding from the Bill and Melinda Gates Foundation.
Ho’s team has also come up with a number of engineered antibodies that are even more potent in neutralizing SARS-CoV-2. Columbia University has submitted a patent application on many of these antibodies.
Antibodies may have a role in prevention and treatment even after effective vaccines become available and vaccination is widespread. A vaccine may not work well in the elderly, Ho says, in which case the antibodies could play a key role in protection.
Convalescent Plasma Trial Completes Enrollment
Convalescent plasma—the liquid portion of blood obtained from COVID-19 survivors—is rich in antibodies and could be used to either prevent illness in people exposed to SARS-CoV-2 or treat those who are sick with the disease. But convalescent plasma must be rigorously tested before we know if it helps, harms, or has no effect.
A randomized controlled trial of convalescent versus normal plasma in 220 patients with severe COVID-19 has completed enrollment. The trial, sponsored by Amazon, began at Columbia University Irving Medical Center but was moved to Rio de Janeiro when it became difficult to recruit patients locally after the FDA granted emergency approval of compassionate plasma infusions and the incidence of COVID-19 in the New York City metropolitan area decreased. A second trial in 150 patients with mild disease, sponsored by the Skoll Foundation, will start in Rio de Janeiro at the end of November.
One advantage of convalescent plasma versus monoclonal antibodies is that antibodies in convalescent plasma are directed against a wide range of viral targets; thus, viral mutation is less likely to impair its utility. In addition, many locations in resource-limited settings are able to collect plasma, making convalescent plasma potentially more accessible than monoclonal antibodies in these regions. On the other hand, monoclonal antibodies are manufactured to a consistent standard while each convalescent plasma unit is different.
Members of the convalescent plasma team at Columbia include faculty from the Vagelos School of Physicians and Surgeons and the Mailman School of Public Health: Max O’Donnell, MD; Jessica Justman, MD; Andrew Eisenberger, MD; Steven Spitalnik, MD; Thomas Briese, PhD; Eldad Hod, MD; and W. Ian Lipkin, MD. The Brazilian team is led by Beatriz Grinsztejn, MD, PhD, of FioCruz.
Antivirals for Today’s Pandemic—and the Next Coronavirus
This year's pandemic is the third major coronavirus outbreak in the past 20 years, and more are likely in the future. Several hundred coronaviruses are in active circulation among animals, many with the potential to jump into humans.
The lab of Alejandro Chavez, MD, in the Department of Pathology & Cell Biology has been working to find potential antivirals that not only fight SARS-CoV-2 but also act broadly against other coronaviruses, including those that may emerge in the future.
Drugs that inhibit viral proteases have been effective against HIV and hepatitis C, so the lab has focused on finding similar drugs that target coronavirus proteases (which the virus needs to replicate).
As described in The New Yorker in April, Chavez’s lab designed an inexpensive method to rapidly screen potential inhibitors against a wide array of proteases at once. “Usually compounds are screened against one target at a time, but that only gives you one answer,” Chavez says. “We realized we needed to change the way drug screens are performed.”
After several months of perfecting the method, the lab is now screening thousands of potential compounds and has already identified novel inhibitors that work against the 3CL protease from many different coronaviruses.
The lab is also working with David Ho, MD, from the Department of Medicine and Brent Stockwell, PhD, from the Departments of Chemistry and Biological Sciences to design even better versions of the inhibitors.
“We’ve found a few compounds that are better than the most potent published protease inhibitors, and we are hopeful that we can continue to develop these molecules into best-in-class compounds,” Chavez says.
The Power of Far-UVC Light
At the beginning of the pandemic, a team in the Center for Radiological Research led by David Brenner, PhD, had already been working for several years on a technique that safely zaps airborne viruses with a narrow-wavelength band of UV light.
Physics suggests that far-UVC light (with a wavelength of around 222 nm) can inactivate viruses floating in the air but cannot reach or damage any living cells in our skin or eyes. This means that fixtures emitting far-UVC light—unlike germicidal UVC devices that emit at 254 nm and can cause skin and eye problems if people are directly exposed—can continuously disinfect rooms with people around.
“Together with masks and social distancing, far-UVC light has the potential to significantly reduce the risk of person-to-person spread of viruses in indoor places,” Brenner says.
The team has already found, in tissue culture and in mice, that short-term exposure to far-UVC is safe and does not damage skin or eye cells, confirming what physics predicts.
A study of long-term exposure in mice is just finishing; hairless mice exposed to far-UVC light for eight hours every day for 15 months are now undergoing eye and skin tests to look for any damage, though none has been found so far.
Based on lab experiments and measurement by others on the sensitivity of SARS-CoV-2 to UV, far-UVC could potentially inactivate 90% of coronaviruses in the air in approximately eight minutes at current regulatory limits. Based on measurements by Brenner's team, other researchers have modeled the effect of far-UVC in indoor spaces and concluded that far-UVC can provide about the same level of protection as can be achieved with either N95 masks or social distancing.
Since the pandemic began, more companies have started to sell far-UVC lights and fixtures, and restaurants and other businesses have begun to install them.
Brenner’s far-UVC team is now preparing to measure how well far-UVC fixtures work in these real-world settings and has started by sampling several New York City locations to measure which viruses are most prevalent in the air.
A PCR test developed by Columbia researchers to detect SARS-CoV-2 has been licensed to SummerBio, a company that uses automation and robotics to enhance the efficiency and reduce the costs of molecular diagnostics. SummerBio is conducting COVID-19 testing for UCLA and Los Angeles Unified School District, as reported by the company in mid-November.
The Triplex CII-SARS-CoV-2 rRT-PCR Test was developed by Nischay Mishra, PhD, of the Center for Immunity and Infection in the Mailman School. The company has also licensed the center’s respiratory differential diagnosis test that includes influenza A and B as well as SARS-CoV-2.
Point-of-care tests for detection of SARS-CoV-2 and other respiratory viruses are also being built at the center by Ian Lipkin, MD, and Thomas Briese, PhD, together with Ken Shepard, PhD, in the School of Engineering. These tests use single chain llama antibodies and electronic circuits, will be inexpensive and rapid, and may allow the screening needed to open spectator events, travel, and schools.