Dr. Seetha Lakshimi and medical team members with Tampa General and USF at work in the Global Emerging Disease Institute at Tampa General. Courtesy of Tampa General Hospital
Dr. Seetha Lakshmi, Medical Director for the Global Emerging Disease Institute at Tampa General Hospital, and Assistant Professor, Division of Infectious Diseases and International Medicine at USF Health. Courtesy of Tampa General Hospital
Last week, the World Health Organization reported that a new version of the Omicron COVID-19 virus, BA.2, is circulating in numerous countries, adding yet another layer of confusing terminology around the global pandemic.
To be clear, COVID-19 refers to the disease people can get while SARS-CoV-2 is the virus that causes COVID-19.
There are now two main mutant variants of the virus circulating in the U.S.-- Delta, and more recently, Omicron.
And Omicron, it turns out, has three subtypes or subvariants -- BA.1, BA.2, and BA.3. Each subvariant shares with the other two many -- but not all -- of the Omicron gene sequences. The original subvariant, BA.1 has been and continues to be the most prevalent one by far. More recently, BA.2, dubbed “Stealth” has now been found in 50 countries, most extensively, in Denmark.
To learn more about this new BA.2 subvariant, Dr. Bruce Shephard, a writer for 83 Degrees Media, recently interviewed Dr. Seetha Lakshmi, Medical Director for the Global Emerging Disease Institute at Tampa General Hospital and Assistant Professor, Division of Infectious Diseases and International Medicine at USF Health.
Below is their discussion, edited for length and clarity.
Dr. Shephard: How do you combine your separate roles, one in public health, the other in clinical medicine?
Dr. Lakshmi: My time is divided between patient care and working to create the next generation of pandemic response. My research experience evolved around therapeutics and the transmission of infectious disease. We have a huge research team that works collaboratively between TGH [Tampa General Hospital] and USF Health [University of South Florida] on the front lines of the pandemic.
Dr. Shephard: What is this new Omicron subvariant?
Dr. Lakshmi: The correct name is BA.2. We call it a sublineage. The popular media calls it “the Stealth variant.” It’s not a completely new variant -- more like a sibling. If there is good news in all of this, it’s that the spike mutation changes are not all that different from the original Omicron. … You have to do gene sequencing to find out what it truly is, which takes 4-5 days.
Dr. Shephard: Where was BA.2 discovered?
Dr. Lakshmi: Denmark was one of the first reported places. When we saw what happened with Omicron in South Africa, we thought the epidemic curve would be the same -- go up fast, come down fast.
Then in Denmark when their caseload did not come down right away, we started asking, has the virus changed? Has human immunity changed? But because human immunity cannot change that fast, the hypothesis was maybe the virus has changed. Then they looked at virus sequencing and noticed that, in fact, it had changed. It appeared even more transmissible than the original BA.1 sublineage. Now we’re looking at how different this one is going to be. And what it means at a patient level.
Dr. Shephard: What do we know about BA.2’s clinical manifestations so far?
Dr. Lakshmi: The short answer is we don’t know a whole lot yet. We expect, based on not much change in the spike protein, that the vaccines hypothetically should still work for vaccinated, boosted individuals. If you’re unvaccinated, then we have no idea.
Dr. Shephard: Is this virus mutating the same way as the influenza virus, like a recurring disease, which changes from year to year?
Dr. Lakshmi: The process is similar but the pace and the steepness of the curve is different. And that’s the problem. In an endemic state -- which means the virus is widespread in the population -- we want virus spikes to be less and less frequent, a blunted curve with more spaced-out peaks. The problem is that every few weeks we have new mutations to contend with, so the pace is much faster and we are still in the pandemic (ie, global) phase. The hope is that it will become endemic. The way I look at it, pandemics have either social ends or medical ends. Social ends have been when people are ready to move on, but the virus isn’t. The medical end is when there is truly a decrease in deaths and numbers of cases. Medical ends often happen much later than social ends. We are now in a transition time between the social and the medical end.
Dr. Shephard: In thinking about the social end of a pandemic, do people usually become less willing to use preventive measures or is it a matter of the limits of these measures?
Dr. Lakshmi: When we talk about social ends, it is helpful for public health folks to understand that this is an expected reaction when people might not be able to comply with the [preventive and safety] measures that have been put in place. Each person ends up doing a risk-benefit analysis for themselves and for their families, rather than looking at a larger public health outcome.
When you look at medical ends for pandemics, there are three subdivisions within that medical end. The starting one is [developing and distributing] vaccines which can sometimes have a sterilizing immunity like the polio vaccine. That ending hasn’t happened with COVID yet. The second subdivision is when a significant portion of public develops enough natural immunity to avoid lots of frequent outbreaks or peaks. That, too, has not yet happened with COVID. The third scenario is essentially a balance of the first two in which the disease becomes endemic. Unless there is a major shift in the immune status of the population or the virus, no major change can happen. But if there is a major change in either, peaks and valleys will ensue again.
Dr. Shephard: Is it likely that COVID-19, like some other viruses, will tend to become less and less clinically severe with recurrent iterations?
Dr. Lakshmi: That’s the question that’s on everybody’s mind right now. Before 2020, I had a Grand Rounds lecture in Atlanta entitled “Pandemics and Human Evolution: Impact on Human Genetics, Culture and Art.” If you look at the endings of all the pandemics, historically, there is always at some point this headline: “It’s over.”
That’s not yet the direction we are headed.
One reason researchers study infectious disease is that there are always challenging changes that depend upon random mutations of viruses. It’s part of human evolution, but it’s not so much fun when it’s happening on your doorstep.
If you look at it from a population perspective of human immunity versus viral change, that is where equilibrium lies. There is no guarantee that there won’t be an impactful mutation at any given moment. The good thing with battling most flu in society is that outbreaks are paced enough [seasonal] so that you have a breathing space in between. That’s where we need to go. Having outbreaks of a COVID variant every two months -- that’s hard.
Dr. Shephard: So, is it possible that COVID-19 will not behave like the flu and call for a completely different paradigm in terms of public health responses?
Dr. Lakshmi: That’s the million-dollar question. There are two ways to look at it. The hopeful answer to your question is that even if we have peaks every two months, we’ve gotten really good at damage control. … If you have good therapeutics and good damage control of a virus, but you can’t 100% prevent it [with a sterilizing vaccine], that’s still an acceptable alternative to having an insane amount of deaths. If we can develop a potent variant-resistant vaccine, that would be a whole different [and better] kind of prevention.
Dr. Shephard: With COVID-19, why now?
Dr. Lakshmi: As my mentor once put it “just because something is improbable, doesn’t mean that it’s impossible.” With COVID, you have a perfect storm in terms of globalization. Our mitigation strategies have to take that into account. We can be globally connected when we want to be, so to speak, but a global response has not happened. Just as transmissions don’t happen globally, responses usually don’t happen globally either, at least not yet.
Dr. Shephard: Given the global range of the pandemic how should we approach travel, especially international travel?
Dr. Lakshmi: In the world, we will have to live with this [battle against COVID-19] for a long period of time. For a lot of people, like those with transplants or who are severely immunosuppressed, traveling is not even a possibility right now. You can do it, you can take the risk, but for these individuals, it would be a big risk to take. For most of the general population, deciding whether to travel is going to come down to individual decisions based upon their individual risks.
What we’re lacking right now -- with both intercontinental and intra-continental transmission, and with so much of the virus circulating -- is a good global supply chain response. For example, we now have shortages in the health care industry of important medications.
Lockdowns, as a mitigation strategy, is a double-edged sword. In the beginning [before a virus is widespread], a systematic lockdown with tracking of the virus may be possible and appropriate. But once the virus becomes global, shutting down travel between countries hampers our responses more than it helps us.
Let’s take Denmark, for example. Let’s say we lock down travel to Denmark due to the new BA.2 subvariant. There would have to be two underlying assumptions: One, that this new mutation only exists in Denmark. Second, that the subvariant can be contained within that geographic area.
If you look at the CDC pandemic response, COVID has been a lesson in learning about our traditional steps of pandemic management, which have had to be adopted to a newer world.
The fundamental guidelines are helpful to our understanding. But I think you have to see it through the COVID lens of an interconnected world. What we’ve learned about COVID isn’t from formal education or reading books.
As a health care provider, what I’ve learned is from being here on the frontline.
It’s so disheartening to see patients with no access to available medicines. These are patients who didn’t have to die. So, I think we need a lot more help in damage control until we have a variant-resistant vaccine. But, as far as just the appearance of a new subvariant, I’m personally not so worried about Stealth.
On Monday, the BA.2 Subvariant, thought to be more contagious but less severe than Omicron, had been confirmed in Wisconsin.
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