Dr. Bob Wachter, chair of UCSF’s Medical Department, assembled a team of Grand Rounds panelists Thursday to discuss how the country is faring in the “race between vaccines and variants,” with regional updates from Dr. George Rutherford, followed by presentations on outpatient therapeutics and Covid-19 variants.
State of the Pandemic
Rutherford, professor of epidemiology and director of UCSF’s Prevention and Public Health Group, began with his usual hoard of maps and regional covid statistics, noting that coronavirus cases are steady in the United States, but falling in California. There have been over 33 million cases of Covid-19 nationally, or 50,000 to 60,000 cases per day.
“The good news is, it’s not going up. The bad news is that it’s not going down,” Rutherford said, highlighting the lower peninsula of Michigan and the area “in and around New York City” as cluster sites.
Death rates are falling in both the United States and California, which is averaging around 2,700 cases and 200 deaths per day. The death rate in California “needs to go down substantially further before anybody is going to be satisfied,” Rutherford said.
Rutherford noted that Michigan has the second-worst case rate in the country; 37 cases per 100,00 people. Its positivity rate is 11.3 percent. Michigan also has the second-highest rate of the B.1.1.7 covid variant, also known as the UK variant. A quarter of the population has received at least one vaccine dose.
“It’s a race between the variants in the vaccines, and here, the variants seem to be winning,” Rutherford said.
In California, there are close to 2,700 cases per day, and the state is “continuing to have declines,” Rutherford said. The state is currently below early fall case levels.
Some 15.5 million vaccine doses have been administered statewide, with 26.6 percent of the population having received at least one dose and 12.9 percent fully vaccinated. Governor Gavin Newson announced today that on April 1, California will give preferential treatment to those 50 years or older, and on April 15, everyone will be eligible to receive the vaccine.
In San Francisco, which is now in the orange tier, almost 447,000 people (51 percent of the population) have gotten their first dose. Rutherford noted this number is slightly misleading because there are many healthcare workers in San Francisco, and because people who work but do not live in San Francisco are eligible to be vaccinated.
Brazil has now surpassed the United States as the country with the greatest number of cases in the past two weeks, followed by the United States, Italy, France, and then India. Rutherford said that the United Kingdom is faring better than other European countries because it has vaccinated more people.
In contrast, European Union residents experienced vaccine delays as the EU negotiated lower prices. The UK also chose to delay giving second doses in favor of giving out more initial doses, a strategy that “seems to be working pretty well,” Rutherford said. Second doses will now be administered twelve weeks after the first dose, instead of four.
Rutherford noted that spring break in Miami has the potential to become a large amplifying event. Florida is the state with the most B.1.1.7 variant cases, and this behavior “could easily feed a fourth surge across much of the country,” Rutherford said.
Wachter mentioned that states like Florida have experienced similar case rates to California, despite having “acted badly” regarding reopening policies. Rutherford said those visitors to Miami will disperse to other states, not factoring into Florida’s rates.
Outpatient Therapeutics
Dr. Annie Luetkemeyer, UCSF professor of medicine, came on next to speak about treatments for individuals who aren’t hospitalized. These interventions are important, Luetkemeyer said, to reduce symptom duration and intensity, break the cycle of infection, decrease risk of severe disease and hospitalization, and potentially limit long-term impacts of covid.
Currently, the only authorized outpatient treatment is monoclonal antibodies, proteins produced in a lab to fight covid that mimic antibodies created by the body. Monoclonal antibodies are administered via intravenous drips (though intramuscular injection with a needle is currently being investigated). These are single-dose treatments, and two are currently approved in the United States: REGEN-COV2, by Regeneron, and a cocktail of bamlanivimab and etesevimab by Eli Lilly and Company. Both target the receptor binder domain of the virus.
For people who were given REGEN-COV2 within three days of diagnosis, the treatment showed an “impressive relative risk reduction” of 70 percent regarding hospitalization and death, as well as a decrease in symptoms and viral load. The Lilly cocktail also showed similar results.
But there are also problems. REGEN-COV2 appears to work against variants; however, bamlanivimab (one of the two monoclonal antibodies in the Lilly cocktail) appears ineffective against all variants, except for B.1.1.7. That failure lead to a public health alert in California last week that said not to use bamlanivimab, Luetkemeyer said. Nevada and Arizona are also no longer distributing bamlanivimab.
The application also has challenges. Treatments need to be administered within 10 days of the onset of symptoms and should only be used with high-risk patients, meaning the “vast majority of people getting outpatient covid … won’t qualify,” Luetkemeyer said.
She also discussed studies on four other potential avenues for outpatient treatment: ivermectin, colchicine, fluvoxamine, and vitamin D, but said that none are ready for outpatient clinical use.
Variants and Vaccines
Dr. Adam Lauring, an associate professor of Internal Medicine at the University of Michigan finished Grand Rounds with his “variant consumer guide.”
Lauring gave an overview of four key variants: The B.1.1.7 variant is approximately 50 percent more transmissible, and there is “accumulating evidence that it does cause more severe disease,” Lauring said. The B.1.351 variant, also known as the South Africa variant, “also seems to be a more rapid spread and transmissible” and has three mutations that “appear to be particularly concerning in terms of its ability to escape preexisting immunity.” The P.1 (Brazil) variant is a concern for immune escape, meaning reinfection can occur. The B.1.427/B.1.429 variant, also called the California variant, has a mutation that appears to affect antigenicity (viruses’ capacity to bind to specific antibodies).
So far, the vaccines appear to be holding up against the variants. The J&J vaccine has 72 percent efficacy in a study of the United States, but was slightly less effective in Brazil (68 percent) and South Africa (64 percent), where variants exist. The Pfizer vaccine shows 85 percent efficacy in a study of the UK when the B.1.1.7 was highly prevalent. Novavax also proved 89.3 percent effective in the UK, but was only 60.1 percent effective in South Africa in a study of HIV negative individuals with high B.1.351 prevalence.
Asked which variant he thinks will win in a “competition” against the others, Lauring said, “I think B.1.1.7 will win, because the advantage in terms of spread — its transmissibility — is significant.” However, he noted that “a lot is going to depend on the complexities of how immunity develops in our population over time.”
Though he is typically optimistic, Lauring was uncertain regarding normalcy this summer. “The United Kingdom did not control B.1.1.7 by vaccination. They controlled it with a lockdown and vaccination,” he said. “It does worry me how we’re kind of approaching this and thinking about it as a vaccination problem.”
See our previous Grand Rounds coverage here.