Spotlight on coronavirus vaccines overshadows furious effort to find new treatments

Might protection from COVID-19 be found in drugs as simple as pseudoephedrine and arthritis medication? Flaxseed and turmeric extract? Fish oil, ibuprofen, nasal spray, Vitamin D?

Hopes are high that therapeutics might be hiding in plain sight in the medicine cabinet, but evidence remains sparse as research continues. One year into the pandemic, the U.S. Food and Drug Administration has approved just one drug to treat COVID-19, and its effects are modest. A few others, which mimic the work of natural antibodies, have received emergency use authorization, but those aren’t slam-dunks either.

So behind the scenes, with deaths mounting and clocks ticking, researchers work “with an intense sense of purpose” to investigate myriad compounds that might tamp down disease.

The treatment piece of the pandemic puzzle hasn’t captured the public imagination — or as much of the public purse — as has the space-race for effective vaccines. While the quest for therapies has suffered for the lack of laser-focus and high-level organization that propelled shots so swiftly into arms, developing therapeutics that can tame COVID-19 is vital to saving lives, researchers say. Millions won’t have access to vaccines for many months — or longer. Some can’t, or won’t, get vaccinated. A tiny fraction of vaccinated folks might not respond to the jabs.

And many expect COVID-19 to be with humanity forever.

“We’re on the lookout for therapeutics to help people who aren’t sick enough to go to the hospital, which is the vast majority of people who get COVID,” said Prasanna Jagannathan, infectious disease specialist at Stanford Medicine and assistant professor of microbiology and immunology.

Most patients recuperate at home without much drama, but an alarming number — assumed to be well on the road to recovery — were suddenly slammed with crushing waves of symptoms that the phenomenon got a name: “The second-week COVID crash.”

“We saw what happened with this recent surge,” said Judith S. Currier, chief of UCLA’S Division of Infectious Diseases in the Department of Medicine. “When people are diagnosed as outpatients, they’re told to stay home and wait to see if they get sick. We have some idea of which people are at higher risk of getting very sick, of who needs to be in the hospital — but it’s not perfect.”

The tricky part of finding a drug that works early in the infection cycle has been finding enough people with fresh COVID-19 diagnoses — long before there’s a “crash” or need for hospitalization — to participate in well-designed studies of drugs that might forestall the virus’ progression.

“Our study mantra is, ‘Rise above COVID,’ “said Currier, who’s also chair of the global AIDS Clinical Trials Group, which is leading some COVID trials for the National Institutes of Health. “The whole idea is to bring people together to contribute to finding the answers. We encourage people to think about how they can help advance science — it’s something they can do. We need to be prepared for the future. Participants have found the process really rewarding and we are so grateful for their contributions.”

Those who have very recently been diagnosed can find a study to participate in at www.riseabovecovid.org/en. In Northern California, studies are underway at UC San Francisco, Stanford University, VA Northern California Health Care System, UC Davis and several other sites. In Southern California, they’re underway at UCLA, USC, UC Irvine, St. Joseph’s Clinical Research, Riverside Medical Clinic, Loma Linda University Health and several other sites.

“It’s all hands on deck,” said Sarah Doernberg, associate professor in UCSF’S Division of Infectious Diseases, medical director of Adult Antimicrobial Stewardship at UCSF Medical Center and site investigator for the trial. “Many scientists have pivoted their focus from whatever they were doing — which was probably not studying coronaviruses — to focus on identifying treatments and understanding the immune response. That piece has been really inspirational to see.” Today’s tools Today, there are few tools in the toolbox.

“Unfortunately, that’s one area where we’ve not made that much progress,” said Edward Jones-lopez, an infectious diseases expert at Keck Medicine of USC. “Typically, for other diseases, treatments are developed first, then vaccines follow later. It happens that, for this, the reverse is true.”

The anti-viral remdesivir is the only drug formally approved by the FDA thus far to treat COVID-19, but it’s aimed at hospitalized patients. It can interfere with the virus’ reproduction and may reduce hospital stays by a few days, but it is not a cure.

Eight more tongue-twisting drugs have received emergency use authorization from the FDA — which allows them to be used before their effectiveness has been proven in largescale, randomized clinical trials — but none appears to be a home run, either. They range from the monoclonal antibodies casirivimab and imdevimab, lab-made proteins that mimic the immune system’s ability to fight off harmful pathogens, to baricitinib, an oral tablet used to treat rheumatoid arthritis by blocking enzyme activity leading to inflammation.

The World Health Organization “strongly recommends” that corticosteroids — such as dexamethasone, hydrocortisone or prednisone — be given orally or intravenously to patients with severe and critical COVID-19. Those can tamp down immune system over-reaction to the virus, which has been linked to many deaths.

“For monoclonal antibodies, we have data from multiple studies that suggest they cut down the risk of progressing to severe disease by about twothirds on average, given early in the course of COVID-9, to patients with symptoms but not yet with severe disease,” said Saahir Khan, infectious disease specialist and principal investigator of USC’S Keck Medicine trial site.