(film reel clattering) - COVID-19 cases, deaths and hospitalizations are on the rise in the U.S. More than two-thirds of Americans have tested positive for COVID.

Public health experts say that this may represent a severe undercount.

More and more people are reporting that they're at-home tests are coming back negative, even when they're exhibiting clear symptoms of COVID.

The BA.5 subvariant of omicron is now responsible for more than 78% of infections in the U.S.

So, we are pleased today to host a robust panel discussion with three esteemed speakers, all familiar faces at our weekly briefings.

Dr. Peter Chin-Hong is the associate dean for regional campuses at the University of California, San Francisco.

He is a professor of medicine who specializes in treating infectious diseases.

Dr. Ben Neuman is a professor of biology and chief virologist of the Global Health Research Complex at Texas A & M University.

And, Dr. William Schaffner is professor of preventive medicine in the Department of Health Policy, and professor of medicine in the Division of Infectious Diseases at Vanderbilt University School of Medicine.

I will kick off today's discussion with questions for each of our speakers.

And with that, we begin.

Dr. Neuman, could you please give us some background on the characteristics of the BA.5 subvariant?

What makes this variant more infectious and symptomatic?

- Yeah.

I think those are good questions and I can tell you what is known, but I can't tell you all the answers yet.

So, if you compare the different strains, the original alpha variant had one change in the part of the spike that actually binds to you, the sort of handshake between the virus and yourself.

Beta, gamma and delta had two mutations.

Omicron came along and it had 15 mutations, all of a sudden concentrated in that area.

Now, we have some of these new variants like BA.4 and five, and these things will have 17 or 18 in that area.

And, this is a very small area of the genome about 1% of the genome, but it has about half the mutations that you find in the entire genome.

Some of these things, yeah, only have 40 mutations, and 20 of them will be in that part of the spike!

So, as a result, this is the part that we would like our immune system to recognize, and this is the part that our immune-- that keeps changing.

It's basically under evolutionary selection.

The virus makes mistakes, our body cleans up all the ones it can and what is left, are the ones that are a little more difficult to knock out.

So, what we know from animal studies is that BA.4 and BA.5 cause more disease in hamsters, more disease in the lung and more disease in the airways leading to the lung, which would make it more difficult to breathe if the same thing happened in people.

We don't know for sure to what extent the hamster is like the person in this case, but it seems like a reasonable model for other aspects of the disease.

As for the rest of it, there is some evidence that omicron-like viruses including BA.4 and BA.5, go into the cell in a slightly different way, which should make things a little more difficult for the virus, because it would have to go inside and then be activated, instead of being activated at the surface.

But, it seems to work very well for this virus.

So, right now we can say that these are different.

They evade immunity because they have many changes at exactly the spot where we would most like to have immunity, but most of the rest of the virus is unchanged.

So, when people say, these vaccines or previous exposure will protect you from hospitalization, what they mean is that most of your immune response to other parts of the virus is still going to be intact; very few mutations.

But, the immune response that would stop the infection and stop the symptoms from starting, that is out of whack, and it runs out much more quickly than it did early on in the outbreak.

When you used to get vaccinated it lasted much longer.

But, because we are still vaccinating against the 2019 virus and it is now late 2022, we have a problem.

The virus is not fast, but it does move and we have stood still.

And, the other aspect I would say is that, like some of you who were vaccinated but still got infected, I was also in the same situation.

And, in part that's because I had all the vaccines I was allowed to have under the current regulations.

It's not so much how many vaccines you have taken in your life.

That is good information for a history book!

[Sunita laughs] It is more about how recently you took the last vaccine, because that's the one that really matters at the moment.

- Interesting.

So just to add to that, do the relaxed restrictions on masking contribute to this current surge in infections?

- At least anecdotally, I think they do.

So, in my case, I relaxed my mask wearing to go to one lunch and to-- They came around on the airplane and they had the little cookies and they had the little drink, and I said, 'sure, I'll have those.'

- [Sunita] Right.

- One or the other of those was the time that I got infected.

And, there wasn't anyone coughing on me.

There wasn't any obvious sign.

Nevertheless, I spread this virus to the rest of my family very quickly after I got back.

So, yeah.

It only takes a little lapse and there are very big lapses out there.

I would be surprised if that was not a large contributing factor.

- Thank you, Dr. Neuman.

Dr. Chin-Hong, the Washington Post ran a story about COVID "super dodgers", as they call them, the one-third of Americans who have somehow managed to escape getting infected.

What are your theories regarding COVID "super dodgers?"

Are some people just simply genetically immune?

- Well?

I think the jury's still out, Sunita.

I think that people don't really know.

It's something that's observed, but there are several theories.

One is, is it genetic?

So far, we haven't an unearthed a secret code that makes someone a super dodger, gives some super powers.

We have seen that in other infectious diseases where some people are more resistant to others by genetics.

The most famous one being, of course, HIV due to mutation in the receptor where HIV tries to enter the cell.

And, that has been exploited in therapeutics.

So, I think if we find that answer it will be amazing for COVID, 'cause we may be able to make medicines to try to make people more resistant to getting infected.

The second reason, of course, is behavior.

You know, different people in the household being exposed the, quote/unquote, "the same way" to someone who's in the household, may mean that some people are just a little bit more risk averse than others, up less close-and-personal.

Maybe one is the mom of the baby versus the grandparent who's less intimate with the baby.

Could be that some people are just taking more precautions when they go out.

Hard to really measure, but that's a possibility.

And, even if you wear a mask maybe the viral load is going to get into you at a lower viral load and maybe that may cause you to be more resistant.

The third might be immunology.

People have vaccinated different times, so we know that as Dr. Neuman said, the further away you were vaccinated, the more vulnerable you are.

So, in a household you have different age groups.

Some people have boosters; some people don't.

So, you have a range of actual immunity within the household and that may lead to differential risk.

And then, fourth, I think probably is more likely than not, people who were infected and they didn't know it.

We know that COVID can cause asymptomatic infection.

We know from CDC data, as you alluded to, about 60% of adults have seen COVID before, and this is before this surge even, and 75% of kids.

So, you know, the likely reason is, again comes down to immunology.

Some people are more protected than others, and there's quite a range now within a household, within a community and within the country and the world.

- Just to follow up, Kaiser Permanente released a study suggesting that our, quote, "snotty nose children" might provide parents with some degree of immunity from COVID.

Your comments?

Is this just conjecture, or can we actually draw something from this?

- I think it's an interesting conclusion, because what I have been noticing anecdotally, of course, again not measured, is that people are not testing as often.

So, of course, we know that people are testing at home, but even people are having symptoms and they kind of like-- well, maybe smile.

Maybe you're back to the more optimistic end.

So, not everyone is testing.

So, that snotty nose kid?

Maybe the parent isn't testing; it actually is COVID.

At some point before the snotty nose kid had another snotty nose early on, transmitted it to the parent, parent has protection.

So, in that sense, yes, it is possible that they're giving exposure to the parent and then that protects the parent from a future infection.

We do have a study from-- There have been a few studies, but one that I like from Toronto, is showing that although like the young adults and adolescents may bring the infection into the household, it's the snotty nose kid and the baby that becomes the nucleus to then generate infection within the household, because you're doting on the patient.

In fact, I know many colleagues who have been really religious about not getting COVID throughout the pandemic, but because their kid got infected, you can't really isolate the three year old in a room.

You have to take care of them and then they get infected in that way.

- Right, absolutely.

Given the fact that so many people are experiencing symptomatic infections, even when they are fully vaccinated and boosted, is there any benefit at this point to getting that first or second booster?

- Yeah.

So, I would say it depends on a few factors.

We do know-- I'll just start from the most objective data.

We do know that in omicron the proportion of people who are vaccinated is increasing, who are dying, but still the majority are unvaccinated.

But, of the people who are vaccinated and dying, they tend to be older, like older than 65, and never got a single booster.

So, I think the main message is people should get at least one booster.

That gives you the biggest bang for the buck, particularly if you're older.

Two boosters, for sure, given the recent mortality data; again, very similar.

The longer we go along for those who are older.

Of course, everybody over 50 is eligible for that second.

But, I would say it's even more urgent the older you are.

So, that's for prevention of serious disease, hospitalization, death.

But, if your goal is prevention of infection, we do think that you do have-- It's not long-lasting, like Dr. Neuman said, but you do have some benefit from maybe topping off your antibodies right after the vaccination.

Maybe it lasts six to eight weeks in this current year versus many months.

So, the way some people deal with that is-- you know?

I have to travel internationally to visit relatives or something like that.

If I'm eligible for a booster I'm gonna try and strategically get the shot two weeks before I go somewhere, to kind of top off the antibodies.

It's kind of like you're at a cocktail party and the host is topping off your glass with margarita.

[Sunita laughs] You don't get more antibodies than the glass itself, but you kind of get a little bit more restoration of antibodies, even though they're very imprecise right now.

As Dr. Neuman said, it's not recognizing the new enemy that well, but if you flood the body with nonspecific antibodies it's still gonna be better than if you got vaccinated in, or boosted 2021.

- Thank you.

And then, final question for you.

Many public health experts believe that there is a severe undercount in the number of reported infections, given that the data really only represents people who have gone into a clinic or pharmacy for their PCR test.

Can you comment on that?

Do you also believe that there is severe undercount?

- Yes, 100%.

I think the best data to make us understand what the gap is between the official numbers and the sort of real numbers, is really in wastewater epidemiology or poop epidemiology.

So-?

Because people have become very sophisticated with that.

We know that for example in California, the levels of wastewater virus is very similar to that in January.

So, if you think about that, and in January more people are getting tested than now at least "officially counted."

We have much more than meets the eye.

So, I think we get a clue from wastewater epidemiology in terms of the general magnitude and we can kind of calculate.

So, with that said, some people at Smith, we actually in reality having about three to eight times more infections.

- [Sunita] Wow.

- And, some people even suggest that even though the official counts in the U.S. is like 130,000 cases a day.

It's probably like a million cases a day.

- Wow.

That's...

It's significant.

Thank you, Dr. Chin-Hong.

We segue to Dr. Schaffner.

Dr. Schaffner, a lot of people have received negative results on their home testing kits, even when they exhibit all the symptoms of COVID.

Are home testing kits unable to detect the BA.5 variant?

- Well, Sunita, there may well be two reasons for that.

The first is that COVID is not the only respiratory virus that's out there.

I realize it is the summer and during the summer, we usually do not have many respiratory viruses.

Last summer we had a surge in RSV infections, respiratory syncytial virus.

This summer we're having another small surge of RSV infections, infecting not only children but adults.

Not as large as last summer, at least not yet, but in my part of the country, a clear increase.

And, just speaking anecdotally, there are other respiratory viruses, common cold viruses, viruses that can cause a sore throat, that are now infecting persons.

So, you may test with a COVID test but you may actually be infected with another virus.

So, that's one reason.

Another reason is that I do think and this is more anecdotal, if my colleagues have more academic studies in mind, please chime in.

But, anecdotally, we think that the rapid tests are less apt to give you a positive result in this BA.5 era that we are in at the present time.

And this, if anything, emphasizes what Dr. Chin-Hong has just been saying, that the number of true infections that are out there is many more than the number that we can count.

It's one of the reasons that the CDC keeps focusing on hospitalizations.

They remind us that's the important public health problem.

It makes people most seriously ill; bad for them personally.

It occupies hospital beds, it puts a stress on the healthcare system, and, of course, hospitalizations cost much more.

So, the distinction between number of cases, important for sure, but hospitalizations, very important, will continue.

I think the CDC will continue to focus on hospitalizations.

- Thank you.

Paxlovid was initially considered a good therapeutic but there appear now to be some concerns around it, and many people cannot take Paxlovid.

Could you give us your thoughts on Paxlovid, and actually from a personal experience since you just went through your own bout of COVID, and you and your wife did use Paxlovid?

- We did.

And this, despite the fact that my wife and I were meticulously careful!

So, it's a testimony as to how effective the BA.5 variant can spread.

I'll spare you my little anecdote.

But, in any event, yes, because we have gray hair, we qualified for Paxlovid.

We both took it.

We had no contraindications.

I was taking another medication so we had to adjust that dose, but that went very well.

My wife did have sort of a metallic taste for two or three days.

That did not diminish her appetite, but she said she could sense that, and it was unpleasant.

And, as you know, diarrhea can be a side effect of Paxlovid.

Neither my wife nor I experienced that, thank goodness.

But, not to get into too much detail, (Sunita laughs) we both had a few loose bowel movements, but we did not have diarrhea.

So, yes.

Eligibility for Paxlovid should be determined by your physician.

Paxlovid is now more widely available, and the data would indicate that in addition to vaccination and boosting, it does prevent development of more severe disease.

So, it keeps you on the milder side rather than letting your illness get more serious.

Now, one of the things that we have learned is that there is something called "Paxlovid rebound."

Paxlovid is an antiviral drug.

It interferes with the multiplication of the virus.

As Dr. Neuman said, the virus can attach to you, gets inside your cells, and then wishes to multiply and spread further throughout your body.

The virus is in; you've got a positive test.

So, you take the Paxlovid and that, as I say, "sits on the virus."

It tries to prevent it from multiplying.

Well, you take the Paxlovid for five days; the Paxlovid is sitting on the virus.

Now, you hope that your immune system eliminates the virus.

However, sometimes the virus has just been hiding, and when the Paxlovid goes away, it starts to multiply again.

And so, a relatively small proportion of people can have Paxlovid rebound.

You can get some symptoms after you stop Paxlovid, but usually not for too long and they will get better by themselves.

- Thank you.

Our final question comes from Jorge Macias.

Jorge, you still with us?

If not, I would like to ask a final question.

And, that is a lot of us have taken those home testing kits or we've even gone into a clinic, had our rapid antigen test, our PCR test, and we test negative five days later, but we're still symptomatic.

Is it okay to go back to work at that point with symptoms?

Dr. Chin-Hong?

Would you like to take that on, first?

- Yeah.

So, it all depends on who you're working with.

In the hospital setting, you maybe wanna be more conservative.

But in general, what we've been seeing in omicron, I think as Dr. Schaffner alluded to, is people with a bunch of negative tests and then they turn positive.

So like, if you're at a dinner party and every other person was positive and you're testing negative, I would not be reassured by that.

For an antigen test, you probably need more than 100,000 virus particles to turn that positive.

It's cruder versus a PCR, which you probably get in less than 20, or 10.

So, that's one issue.

The second issue, and I feel nervous saying this in front of the others, especially Dr. Neuman, is that people think that people who are vaccinated and boosted have roving antibodies and immune system that are primed.

So, when the enemy comes, even if it's one or two, it jumps and tells you you're sick earlier versus in the old days when you didn't have any experience and it took a while for your body to tell you that you're sick because that's what tells you you're sick.

So, that's another reason why people may be going later.

And, the third reason is that in the omicron flavors, it starts soft in the large area always, then the throat.

So, if you're just swabbing your nose, it may take some time for it to go up there.

So, some people, even though "unorthodox" in the U.S.; in the UK, they're doing it more.

They combine the throat and the nose together.

- Anybody else want to take that on?

No?

And, any final remarks for many of our speakers before we conclude?

Alright.

- Get vaccinated!

Yeah.

- [Dr. Schaffner] I would say that COVID is going to be with us for the foreseeable future, and we've moved from pandemic phase to now endemic.

And, we're struggling to figure out how we can keep this virus down and minimize its damage and still at the same time enjoy a reasonably normal life.

We're continuing to struggle with that.

Vaccinations with updated vaccines will continue to be an absolutely essential part of that strategy.

We may get new therapies.

Wearing the mask for those particularly who are at high risk, will continue to be useful for those people.

So, we're constantly trying to figure out the best way to balance a more open life with the maximum protection we can get against the virus.

Stay tuned; we're still working on that.

(Sunita laughs) - Dr. Chin-Hong, what are your final remarks?

- My final remarks is that, I mean, I think we're all tired.

All of us on the panel are tired; you're tired!

But, we kind of have to keep carrying our-- Using our toolkits, moving into the future with COVID smarts and we can't ignore it.

I think that's-- But, there are a lot of silver linings.

Like, all of the progress we've made in science, and I think that I'm looking forward to version 2.0 of the boost, and hopefully that will mitigate the disruptions in society that we're seeing.

- Thank you.

Dr. Neuman, you have the final word.

- So, the way I see it, if you have a bigger problem the first thing you gotta try is picking up a bigger hammer.

And, we gotta use the tools that we've got as hard as we can.

I am still, after all of this, optimistic that we can actually drive this virus to extinction.

Now, that is not a fact; that is just an opinion.

Buy, I think it's one that we can chase, and we haven't really started to chase yet.

So, I'm hopeful.

But, yeah.

There's always Plan B, and that's a good outline of Plan B.

- Thank you to all of our speakers.

I don't know if you've noticed in the chat that there are many kudos to the three of you.

We hope you'll join us again at a future briefing.

We've now end.

Take care.

- [Dr. Neuman] Bye bye!

♪