In the absence of FDA-approved treatments for COVID-19, scientists and physicians at Yale-New Haven Hospital are testing a variety of experimental therapies for the disease.
As COVID-19 batters the country and recent models predict upwards of 100,000 deaths in the United States, doctors and pharmaceutical companies are scrambling to find effective COVID-19 treatments. Yale’s Center for Clinical Investigation and YNHH have partnered to participate in clinical trials. The School of Medicine currently has three active trials listed on its website, and YNHH is working on more than 25 additional trials, Thomas Balcezak, chief clinical officer at YNHH, wrote in an email to the News.
“This is a race to find effective and safe therapies for patients,” Medicine professor Onyema Ogbuagu said. In the potentially year-long wait for a vaccine, treatments provide the “most immediate hope,” he added. “We’ll have to treat our way through this before we can prevent it.”
The pandemic progresses so rapidly that YNHH updates its treatment protocol every two days, explained Naftali Kaminski, who is the School of Medicine’s Chief of Pulmonary, Critical Care and Sleep Medicine. Generally, committees change treatment protocols once in every year or two.
YNHH’s COVID-19 current treatment protocol, which was released April 3, calls for the use of experimental medications. Kaminski explained that physicians “in the trenches” fighting the COVID-19 pandemic have to quickly decide how to best help patients. The protocol alleviates that burden, providing a general roadmap for treatment.
YNHH currently has an “aggressive” treatment protocol, Kaminski said, that advises physicians to administer medication more frequently than other hospitals’ protocols specify.
According to Kaminski, doctors will inevitably make errors in treating the disease because they “need to act” and “don’t have all the information.” Despite the risk of criticism should its protocol have mistakes, YNHH has published it online to make it accessible to other hospitals and to receive feedback.
For patients with severe COVID-19 who require supplemental oxygen, the protocol advises doctors to administer Hydroxychloroquine — the malarial drug that President Trump touted as a potential game-changer in COVID-19 treatment — to prevent the virus from infecting more lung cells.
“Hydroxychloroquine is in some ways a little more controversial and in other ways more widely used,” Kaminski said, because the studies that point to its efficacy are limited, and it may cause heart arrythmias.
According to Balcezak, all treatments have side effects. In a March press conference, he emphasized that scientists must consider whether the drug’s benefits outweigh its risks.
Hydroxychloroquine and another drug in the protocol, Tocilizumab — which YNHH has given to more than 70 patients — has been promising, according to Geoffrey Chupp, professor of pulmonary medicine. But he added that these anecdotal results are not conclusive, and doctors need data from controlled trials to have scientific confirmation that the treatments they are using work.
“We need them in this disease, especially this,” Chupp said about proven treatments.”It’s such a dramatic and severe illness and we’re all trying to help and make a difference for these patients.”
COVID-19 is strange among viruses because its effects vary greatly between patients. It is therefore necessary to have different treatments for all levels of severity. Kaminski explained that most patients will present mild symptoms, if any. Around 15 percent of infected people will develop a lung infection and require treatment and observation. And another five percent will go into critical condition and need mechanical ventilation to survive.
As the number of coronavirus cases has surged, researchers have been trialing therapies that have been traditionally used to combat viruses similar to COVID-19 or to manage the same symptoms that COVID-19 patients present. The FDA has streamlined its approval process to accommodate these practices.
Ogbuagu serves as principal investigator for the YNHH trial of the antiviral drug Remdesivir, a drug that halts the replication of viruses. Ogbuagu’s study looks at two groups: patients with moderate and severe coronavirus symptoms.
Since its launch in early March, the trial has already completed the first phase of the severe study and has treated 400 patients. The data from all the sites that participated in the trial will not be released for another two to three weeks, Ogbuagu said, but he has not yet heard of patients experiencing any of the adverse effects associated with this drug.
Chupp is the principal investigator of a clinical trial for Siriluminab, which works by minimizing the overactive inflammatory response some patients’ immune systems produce in response to the virus. Chupp’s study only enrolls patients who are sick enough to require oxygen.
“Because we’re in the middle of a pandemic, the trial’s enrolling really quickly,” Chupp said in an interview while on break from the Intensive Care Unit.
He is awaiting FDA approval for another trial that will treat a significantly smaller pool of critically ill test subjects. The “compassionate use” trial is for treatments approved in other countries but not the U.S., and means that all enrolled patients will receive the therapy and not a placebo.
“Really we’re trying anything we can to save them,” Chupp said.
Both Chupp’s and Ogbuagu’s studies are funded by the pharmaceutical companies that manufacture the drugs. If the trials prove effective, the companies will seek FDA-approval to market the drugs to hospitals as COVID-19 treatments.
Yale researchers are also attempting to enhance patients’ own immunity to COVID-19. To do so, they develop a serum that contains SARS-CoV-2 antibodies from the blood of recovered patients and give the serum to severely ill patients. Doctors believe that patients who have fought off COVID-19 have a high concentration of antibodies. Several such trials are starting now, Kaminski said, as patients begin to recover from the disease.
Yale has also developed a repository of tissue samples from people who’ve had COVID-19, as well as from healthcare workers who may have contracted the virus and recovered without showing symptoms. The samples aid in research of what patients’ bodies undergo when they are infected with the virus and help provide the scientific basis for treatments.
According to Kaminski, researchers had not accounted for the COVID-19 pandemic in their budgets, and none had previously received grants to investigate it. As such, the only money they can access to treat the virus is institutional or personal.
Rose Horowitch | firstname.lastname@example.org