It’s Thursday noon, and time for UCSF’s Medical Grand Rounds on COVID-19. Grab a cup of tea or a stiff drink. We may think the pandemic is subsiding, but Thursday’s 90-minute update was grim.
“Sobering,” said the able and affable moderator Dr. Bob Wachter, chair of the Department of Medicine at UCSF.
Dr. George Rutherford, a professor of epidemiology and biostatistics – back by popular demand, said Wachter — focused this week on COVID’s progression in the United States and California.
“There’s really nothing to suggest that this is dropping off,” he said. “And, in fact, it’s continuing at a fairly flat rate.” The latter equals around 25,000 to 30,000 new cases a day in the United States.
Yes, cases have come down in New York, but they’ve risen elsewhere – in places not even Rutherford has heard of, he said.
Rutherford’s not happy about Georgia and other states re-opening. “This great rush to recreate the economy and to get the economy going again will be paid for in blood, quite frankly, and it’s not going to be evenly distributed across the population,” he said. “That’s going to be on the backs of Latino and African-American populations.”
If anything is consistent in the virus’s progression, it’s that black and Latinx folks are dying at disproportionately higher rates than whites.
While Rutherford supported opening in places like Modoc Country in northern California, he said, “I think you have to be really really careful about doing this. Obviously you have to trade off against the economy … But, you know, just understand that we’re trading the economy for lives.”
When Wachter asked where the new cases in San Francisco are coming from, Rutherford responded, half in jest: “Dolores Park.”
But the answer was, of course, was more complicated than residents violating the shelter-in-place orders and gathering in the city’s parks. The new cases, he said, are essential workers, who “really have to go out and work every day … people who are coming in from the outside … people in large households … multigenerational households passing the infection from one person to another, serially. So those are the deals where the cases are coming from.”
Comparing the virus’s trajectory to the 1918 Spanish flu, he said, “We’ve now plateaued well off of baseline, and we’re headed for potentially a very large outbreak in the fall, which will make whatever we’ve seen pale in comparison.”
One characteristic of the virus that could help blunt the second wave: it is less transmissible among children.
Vaccines and treatments
Dr. Joel Ernst, professor of Medicine and Chief of UCSF’s Division of Experimental Medicine, said a vaccine is particularly important for COVID-19, because researchers found that, with SARS, protective immunity began to “wane between a year and two years after infection.”
“So, unlike things like measles or smallpox, where infection confers lifelong protective immunity, coronavirus infections may be an exception,” he said.
The interim remedy was the territory of Dr. Nevan Krogan, professor at UCSF and director of Quantitative Biosciences Institute.
Krogan said researchers are looking at two different classes of treatments: one that attempts to find drugs or compounds to use against viral proteins. The other, which his team is working on, is to identify human proteins that the virus needs, and then test drugs and compounds that target those proteins.
“The virus cannot live by itself,” he said. “It needs us, our genes.”
To find treatments, Krogan’s team is primarily working to repurpose drugs already approved by the FDA, or drugs in clinical trials.
Neither vaccines nor treatments will be easy to find
Donald Ganem, professor emeritus of Medicine in Infectious Diseases and head of infectious disease research at Novartis from 2011 to 2018, reminded listeners of the difficulties the science community faces in finding either a treatment or a vaccine.
The common cold, for example, is a coronavirus — and, nope, there’s no vaccine for that. “For this virus family,” he said, “the prior track record of producing vaccines has not been good.”
On the treatment end, Ganem spoke first about Gilead Sciences’s remdesivir, which the FDA recently approved for use in COVID-19 patients.
“The fact that you have to use it by intravenous administration means nobody can get this drug until they’re sick enough to come into the hospital,” he said. And then? “Remdesivir works a little bit, and tells us that orally bioavailable replication inhibitors could do a lot better.”
Given all that we’ve learned about remdesivir on Grand Rounds, the “promising” adjective the media often uses to describe it might be overstating its prospects.
Wachter asked the panelists to look into their crystal balls for what the game-changer in controlling the virus would be and when it would appear.
Ernst, who is working on vaccines, went first: “July 14, but I won’t tell you what year.” Wachter prodded. Not until 2021, Ernst said, adding that treatments would come first because of the safety requirements for a vaccine.
Melanie Ott, the senior investigator in the Gladstone Institute of Virology and Immunology and a professor at UCSF, who talked earlier about her team’s work on 29 proteins and the Viral Library Project, agreed. She speculated that by early 2021 there would be more than one treatment and different combinations of treatments.
Nevan, who is working on drug therapies, offered something more optimistic: “considering all these great minds collaborating, working together,” he hoped to see “a more powerful drug regimen by the end of 2020.”
Ganem, who described himself as “the skunk at the garden party here,” was indeed just that. He said “repurposing” existing drugs like remdesivir is not going to provide the game-changer the world is waiting for.
A game-changer, he said, “That’s asking for an awful lot. The best we can hope for from repurposing is a partially effective drug that maybe limits mortality somewhat … ”
And a vaccine?
“…a partially effective vaccine might happen in three years or so.”
You can watch the whole program here.
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