UC San Diego panel looks at past, present and possible future of ‘A COVID World’

As the second anniversary of the announcement that COVID-19 had reached the United States approaches in January, UC San Diego presented an online forum Dec. 2 that looked at the brief past, the present and the possible future of the disease.

Hosted by Kit Pogliano, dean of the Division of Biological Sciences, “A Deep Look into COVID-19: Adapting to a COVID World” featured professor of medicine Natasha Martin, biological sciences associate professor Justin Meyer and biological sciences professor Elina Zuniga.

The panel addressed topics including how SARS-CoV-2, the coronavirus that causes COVID-19, has evolved and spread in the community, the current variants, what scientists are learning about how to fight the virus and more.

The past

“I think one of the most annoying parts of this whole pandemic has been that advice on how we can handle the pandemic has changed over time,” Meyer said. “And yes, sometimes communication is poor from public officials, but really the changing advice has a lot to do with the fact that the virus we are dealing with today is not the same virus that first emerged.”

He said the virus has evolved and adapted and is better able to spread in the human population than the version that arose in late 2019 and soon shocked the world.

“This summer, as the Delta variant strain began to spread, it dominated and outcompeted all other strains,” Meyer said. “As it began to spread, it triggered this massive wave in the United States and around the world.”

Meyer said changes in the proteins on the edge of the virus “play a big role in the virus’s ability to spread. If it can improve its ability to do this through mutation, that is going to allow the virus to spread faster and faster.”

The Delta variant is 2.2 times more transmissible than the original, he said.

The mutations also can hinder our immune system’s ability to fight them, Meyer said, though “that’s not to say the vaccines are not effective; they are really still very effective.”

The present

Meyer recorded his portion of the forum Nov. 29, soon after news had broken about the virus’s Omicron variant.

“We don’t have much data on its characteristics,” Meyer said. “I’m hoping the science will reveal more in the coming days.”

Speaking to the science that her lab is engaged in, Zuniga focused her talk on the role of interferons and plasmacytoid dendritic cells, or PDCs, in fighting viral infection.

“In addition to the great suffering that COVID has brought to people around the world, it has also brought to the forefront of the general public the importance of understanding antiviral defense, because it is only through a deep understanding of how our body protects us against viral infection that we can devise rational therapies,” Zuniga said.

Interferons, she said, are proteins with different “flavors” that can signal an antiviral response when activated. PDCs are “the most powerful interferon-producing cell; they are like interferon factories.”

“Almost any cell is able to produce interferons in response to a viral infection,” Zuniga said. “When a virus infects a cell, it exposes the viral RNA or DNA that will then be sensed by selected receptors that trigger a signaling cascade that will lead to the activation of this interferon gene.”

That will trigger another signaling cascade that leads to the activation of another group of genes that creates an antiviral state in the cells where the interferon receptor has been engaged, she said. “That prevents or severely restricts the growth of the virus in the infected cells.”

COVID-19 is susceptible to interferons and interferon-stimulated genes that restrict SARS-CoV-2 growth or prevent infection of uninfected cells, Zuniga said.

The good news, she said, is “we have these cells [PDCs] that produce a phenomenal amount of interferons, and they are less vulnerable to the antagonistic effect of viruses. … The bad news is it’s not as good as it could be, because after producing interferons, PDCs become dysfunctional.”

Since the lab started looking at the role of interferons and PDCs, “we have advanced our understanding of the mechanisms and this PDC dysfunction,” Zuniga said. “Our lab has identified multiple genes that are downregulated in these dysfunctional PDCs and we have shown recently that by recovering at least one of these genes and restoring its expression, we can restore the interferon production capacity in these otherwise dysfunctional PDCs.”

Answering a question from the audience about integrating interferons into therapies, Zuniga said some therapies that involve delivering interferons are showing “promising results,” though she hopes to see more data.

Martin spoke about UC San Diego’s “Return to Learn” program, which launched earlier this year to implement rigorous coronavirus testing and screening for people on campus.

“Generally, the campus is really well-situated to meet the challenges of Omicron,” Martin said. “We have highly vaccinated students, faculty and staff. We have a robust testing program and a really engaged student population that has participated in our initiatives.”

She added that a “chancellor’s challenge” aims to provide booster shots to 10,000 students by Jan. 1.

The future

While much is not known about the future of COVID-19, Meyer said mathematical models indicate “it’s going to be very difficult for us to reach herd immunity … and get enough vaccinations and enough resistance for us to wipe out this virus. ... What it means is that this virus is going to stick around for a while and we have to adjust the way we fight disease and modify our behaviors going forward.”

“Coronavirus is probably here to stay and going to be a new seasonal respiratory disease similar to influenza,” he added. “The good news is, as more and more people get vaccinated, the virus will have a hard time spreading and will behave more like influenza in the number of people that are infected each year. There should also be less death and less sickness because we will have some level of immunity from vaccines and natural exposure.”

Meyer said he doesn’t expect the general public will need a yearly vaccination, “but it’s hard to know exactly what to expect as this thing changes.” ◆