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Omicron variant is likely to come to Philly region. This Penn lab may be the first place that spots it.

Work being done at University of Pennsylvania will help clarify the omicron variant's ability to spread and cause serious illness, and how well existing antibodies will hold up against it.

Frederic Bushman, chair of microbiology at University of Pennsylvania's Perelman School of Medicine and co-director of The Penn Center for Research on Coronavirus and Other Emerging Pathogens.
Frederic Bushman, chair of microbiology at University of Pennsylvania's Perelman School of Medicine and co-director of The Penn Center for Research on Coronavirus and Other Emerging Pathogens.Read morephoto courtesy Penn Medicine

When the omicron variant inevitably arrives in the Philadelphia region, the Penn Center for Research on Coronavirus and Other Emerging Pathogens is expected to be a critical resource in identifying the COVID-19 variant and tracking its movement.

The lab regularly sequences the genetic material in samples drawn from positive COVID-19 tests, hospitalized patients, even animals, in an effort to understand how coronavirus is transmitting and evolving in the region. Penn and another sequencing lab at Children’s Hospital of Philadelphia work closely with the city, Philadelphia Health Commissioner Cheryl Bettigole said Wednesday. The city can send samples to the CDC, but it’s faster to get it done locally.

”The U.S. as a country doesn’t do nearly enough sequencing,” Bettigole said. “Very few cases in the U.S. overall are sequenced.”

The city is exploring the possibility of creating its own sequencing unit, she said.

Once scientists know the sequence of the building blocks that make up the virus’ RNA — the genetic material that determines the virus’ structure and function — scientists can determine how mutations among COVID-19 variants affect the virus’ ability to spread, infect cells, and make people sick. Routine sequencing of positive COVID-19 cases in South Africa led to the discovery of the omicron variant.

Right now, virtually every case in the region is the delta variant. The first case of the omicron variant has shown up in California, though, and when the omicron variant arrives locally, the center should be able to spot it by sequencing the virus’ 30,000 RNA bases. That process, repeated as new samples come in, gives local hospitals and health officials an idea of how prevalent each new variant is in the region, while adding those data to similar information being gathered around the world to understand how new variants are spreading.

Frederic Bushman, chair of microbiology at University of Pennsylvania’s Perelman School of Medicine and codirector of the center, recently spoke with The Inquirer about the center’s work and what can be learned once the genome is sequenced. This interview has been edited for clarity and concision.

Have you seen the omicron variant yet in local COVID tests?

We’ve been sequencing away. We just did a batch over the weekend that brings us into November. We’ve not seen omicron yet. We’ll continue doing this kind of surveillance sequencing indefinitely. I think it’s likely we’ll see omicron sooner or later, but we haven’t seen it yet.

How many labs are working on sequencing COVID-19?

All over the world there are labs sequencing SARS-CoV-2. Each one is most commonly working with local samples, so it’s a mechanism for global surveillance. If you were all sending your samples to a single central site it would be much slower. The samples are perishable, so it’s good to go to the local freezer, pull them out, and work them up instead of trying to ship them all over the world. Once viral genome sequencing is completed, results are sent to global databases for ongoing analysis.

How long will it take to sequence the variant once you find it?

If somebody’s working flat out it would take, I don’t know, two or three days. Usually it takes a little longer.

What are you looking for when you sequence the genome?

We are looking for changes in the genome sequence that specify the variant, and changes that we can infer will influence the properties of the virus. The virus particle has on its surface a spike protein, and that spike protein binds to a receptor on human cells, the ACE2 protein. And that programs fusion of the viral membrane with the host cell membrane and the entry of the viral genetic material into a cell.

[A few features of omicron appear noteworthy, Bushman said. It seems to be better at binding to those human cell receptors and entering cells.]

The inference is there’s improved transmission.

Also there are changes in the spike protein that will block binding of some antibodies. These can be human antibodies induced during infection, so the virus can evade some components of the human immune response. And as you probably know there are monoclonal antibodies that can be used to treat people. You can see a bunch of changes in omicron that will likely block many of the commercial products, the monoclonal antibodies you can use for therapy, so that’s something we’re paying close attention to. SARS-CoV-2 also has another protein, termed nucleocapsid, that plays a role in allowing the virus to replicate, and where mutations have accumulated that likely allow more efficient infection.

Is your work done once the genome is sequenced?

Understanding what we’re seeing in the sequence is based on lots of different kinds of followup experiments. For example, we can grow virus in a biosafety level-three laboratory, and investigate whether specific antibodies inhibit viral growth.

What are you most interested in learning when you start seeing samples of the omicron variant?

A really interesting question is, if the virus is evolving, what’s going to happen long term? There’s one line of thought that would say that an efficient parasite wants to minimize its burden on the host so as to spread more efficiently. If an infected host is flat on their back, and the pathogen is a respiratory virus, it’s not going to move between people so easily. However, if it’s more benign, maybe it will spread more efficiently.

There’s actually some suggestion that omicron -- very early days, this totally could change -- but suggestions out of South Africa that maybe for omicron the infection is not so bad, so maybe that’s an evolved thing. Maybe that’s a reflection of the fact that it’s really good at spreading in part because it’s not very pathogenic. Of course that’s just one possibility, and time will tell.

Staff writer Laura McCrystal contributed to this article.