As the country rides a new wave of the COVID-19 pandemic, it faces a riptide that’s threatening its course. The delta variant, the now-predominant strain of coronavirus, prompted President Joe Biden’s call for booster shots for all vaccinated adults on Aug. 18 and underscored discussions at a research summit that ran parallel to the president’s nationwide address.
“This is, of course, something that we’ve been looking at for a very long time,” summit keynote speaker Mary Marovich, MD, director of the Vaccine Research Program with the National Institutes of Health, said of the booster announcement just hours before it was made. “And we wanted to make that decision based on science.”
Held virtually again this year, the ninth annual Colorado Clinical and Transitional Sciences Institute CU-CSU Summit included about 150 scientists from the University of Colorado Anschutz Medical Campus, Colorado State University and CU Boulder.
Did you know? On Aug. 23, Pfizer became the first of the three COVID-19 vaccines in use in the United States (so far administered under the FDA’s emergency use authorization) to receive full FDA approval?
“We looked at different vaccines and different combinations of vaccines,” Marovich said of several booster-focused studies with early results suggesting value of a third dose. “We should have more complete results toward the end of this month.”
Pending Food and Drug Administration (FDA) approval, boosters for adults who received the mRNA-based Pfizer (202 million) and Moderna (142 million) vaccines could begin as early as Sept. 20. Johnson & Johnson announced this week that it will submit data to the FDA showing a significant antibody boost from a second dose for the about 14 million adults who received its one-dose vaccine.
Delta variant: A push back out to sea?
Just as the shoreline appeared in sight, with the vaccine rollout sending pandemic infection and hospitalization rates plummeting, two variants of the original coronavirus struck the United States. The variants pushed rates back up, largely in the unvaccinated population.
“We first had the spread of the alpha variant, which caused a wave in late winter and early spring,” said summit presenter Thomas Campbell, MD, a professor at the University of Colorado School of Medicine in the Division of Infectious Diseases.
The delta variant followed, moving into the state in mid-April and rapidly overtaking alpha, Campbell said, noting that the latest waves hit when most safety measures, from mask-wearing and social-distancing, had been removed.
Delta now accounts for almost all new infections today, and the transmission rate and other characteristics of the variant have infectious disease experts on edge.
Delta’s household transmission rate is 64% greater than alpha’s, and delta is almost twice as infectious as variants prior to alpha, said Campbell, CU Anschutz associate dean for clinical research. “There’s also evidence that delta has increased virulence,” he said, noting a study that found an 85% increased risk of hospitalization with delta compared to alpha.
Early evidence suggests the delta variant can be more adept at escaping the neutralizing antibodies created by the vaccines, natural infection and some of the monoclonal antibody therapies that have been game-changers in the fight against COVID-19, Campbell and Marovich said.
Immunocompromised: a more powerful punch
The issues are more pronounced in the nearly 7 million Americans with compromised immune systems, a population that includes cancer patients and organ recipients whose bodies can fail to mount robust protection against the virus after initial immunizations.
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Besides being more apt to develop severe COVID-19, the immunocompromised can suffer prolonged infection, allowing for more viral shedding and evolution of the virus, Marovich said. Of the emerging “breakthrough cases” (coronavirus infections in the already vaccinated), studies find about 40% of the few that end up hospitalized are in these significantly immunocompromised patients, she said.
Based on that science, third doses of vaccines were authorized for the immunocompromised on Aug. 12, Marovich said.
While early evidence suggests recent variants have reduced effectiveness of current vaccines for everyone, the reality remains that nearly all COVID-19 deaths and hospitalizations today are in the non-vaccinated population, Marovich and Campbell said. About 50% of Americans and about 44% of Coloradans remain unvaccinated.
Opening door, fueling power of infection
Vaccines and therapeutics targeting the COVID-19 virus focus on the pathogen’s spike protein, Campbell said. “This is the protein on the surface of the virus that engages the ACE2 receptor on the cell’s surface and allows infection of the cells,” he said.
“These variants are of concern because of the mutations that they have in the receptor binding domain of the spike protein,” Campbell said. Alpha, beta, gamma and delta all have slightly different receptor binding domain mutations that increase their ability to bind to the ACE2 receptors and invade the cells, he said.
The mutations also appear to boost viral spread and reduce the power of antibodies that neutralize the virus’s effect.
“There’s increased respiratory viral shedding that is believed to be a large part of why there is increased transmissibility of both the alpha and the delta variant, and these mutations lead to decreased efficacy of neutralizing antibodies,” Campbell said.
“For people who are high risk for severe or critical COVID, if they have a significant exposure in the community or at home, we can use monoclonal antibodies to prevent subsequent illness.” – Thomas Campbell, MD
Studies suggest the binding domain mutations are also at play in reducing monoclonal antibody treatments. The single monoclonal antibody banlanivimab, widely used during earlier outbreaks, is greatly reduced by the new variants, as is the combination therapy of banlanivimab and etesevimab, Campbell said.
The good news: the combination of casirivimab and imdevimab produced by Regeneron Pharmaceuticals does hold up against the mutations and is the main monoclonal therapy used for treating patients in Colorado, he said.
Treatments help fight, prevent disease
Campbell emphasized the importance of continued research on monoclonal antibody therapies and their value in treatment strategies. Doctors use the therapies not only to prevent severe illness; they can also prevent disease.
“For people who are high risk for severe or critical COVID, if they have a significant exposure in the community or at home, we can use monoclonal antibodies to prevent subsequent illness,” he said.
Monoclonal antibodies are also used in the outpatient setting, when a person who has a high risk of developing severe COVID-19, including those 65 or older, tests positive for the coronavirus.
“It’s important that these antibodies be given early on, within 10 days of the onset of symptoms,” he said of the time frame that involves the highest level of viral replication and shedding (thus transmission to others). “That’s the period where the virus-targeted agents are the most beneficial."
For hospitalized patients, anti-inflammatory therapies are the mainstay of treatment, Campbell said, although anti-viral and monoclonal antibodies are sometimes used in critical patients.
Clinical studies have found an 80% to 90% reduction in hospitalizations and deaths with early monoclonal antibody therapy.
“It’s the vaccines that are going to change the course of the pandemic, not the treatments.” – Thomas Campbell, MD
While treatment advancements are imperative now and for the future, Campbell said it’s important to remember that the vaccines in use still protect very well against severe COVID-19 and death and provide the best way to ride out the waves. “It’s the vaccines that are going to change the course of the pandemic, not the treatments.”
Speakers targeted a range of subjects during the summit titled “Evolving Impacts of COVID-19: Research Advances in Colorado and Beyond.” View the full video recordings on the CCTSI website.
