COVID-19 cases, deaths, and hospitalizations are on the rise in the United States, according to July 22 data from the Centers for Disease Control and Prevention. More than 2/3 of Americans have tested positive for Covid despite most being vaccinated and boosted. This may represent an undercount: more and more people are reporting that their at-home tests are coming back negative even when they are exhibiting clear symptoms of Covid-19. The BA5 subvariant of Omicron is responsible for 78 percent of infections in the U.S.

Is BA5 more transmissible? Is it harder to detect in home-testing kits? Are symptoms of BA5 more severe? How have a mere handful of Americans dodged infection? And is BA2.75 the next threat?

Ethnic Media Services held a panel discussion, July 29, with three acclaimed subject matter experts – Dr. Peter Chin-Hong, Associate Dean for Regional Campuses at the University of California, San Francisco. Dr. Chin-Hong is a professor of medicine who specializes in treating infectious diseases; Dr. Ben Neuman, Professor of Biology and Chief Virologist of the Global Health Research Complex, Texas A&M University; and Dr. William Schaffner, Professor of Preventive Medicine in the Department of Health Policy and Professor of Medicine in the Division of Infectious Diseases, Vanderbilt University School of Medicine.

(Above, l-r): Dr. Peter Chin-Hong, Associate Dean for Regional Campuses at the University of California, San Francisco; Dr. Ben Neuman, Professor of Biology and Chief Virologist of the Global Health Research Complex, Texas A&M University; and Dr. William Schaffner, Professor of Preventive Medicine in the Department of Health Policy. (EMS)

Dr Ben Neuman: Background on the characteristics of the BA5 subvariant

What makes this variant more infectious and symptomatic?

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

“Beta, gamma, and delta had two mutations. Omicron had 15 mutations concentrated in that area.

“Now we have new variants like BA4 and BA5, and these things will have 17 or 18 in that area, and this is a very small area of the genome, about one percent of the genome. But it has about half the mutations that you find in the entire genome.

“Some of these things only have 40 mutations, and 20 of them will be in that part of the spike. As a result, this is the part that we would like our immune system to recognize, and this is the part 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.

“What we know from animal studies is that BA4 and BA5 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.

“There is evidence that Omicron-like viruses including BA4 and BA5 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. 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.

“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.

“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. It is more about how recently you took the last vaccine because that’s the one that really matters at the moment,” said Dr Neuman.

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 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 one or the other of those, was the time that I got infected. 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 vector,” said Dr Neuman.

Earlier on in this pandemic we had hoped that each new variant would be a little bit milder. That has turned out not to be the case, could you explain?

“This is the difference between evolution as non-scientists understand it, and evolution as it actually happens. There has to be feedback in order for an evolutionary change to stick. Something about the virus has to change to make it more likely that that virus will produce more virus particles, infect more people, and spread more widely.

“Now the problem with a virus like this one is that it has usually spread before the symptoms even start, so the virus does not know if it could even know how many symptoms it will cause.

“It has already moved on to the next person, the symptoms are essentially a side effect that happens after all the work that would feed into evolutionary fitness has happened, so unless there is some change, I really think this is a virus that will continue changing, to evade some immunity, but I don’t think there is a strong selective pressure like a strong driving force that would drive the virus to necessarily become weaker.

“It may be that in the fullness of time 10 or 20,000 years into the future, we can say, yes this is not such a bad virus, but it’s a long path from here to there and it doesn’t look good at the moment,” said Dr Neuman.

What about the BA2.75 variant that is emerging in other parts of the world? Is it going to look similar to what we’re seeing with BA5?

“We saw people who caught the original version of the virus, get reinfected with delta about a year later, and delta had two changes in that part of the spike.

“We now see people who caught Omicron around Christmas or January, now getting re-infected with BA4 and BA5 which have four changes. Compared to Omicron, BA2.75 has another two or three changes depending on what you’re comparing it to, so it looks as though it should evade some component of immunity right now. It’s a very new strain and there is not a lot of published literature on it, but just looking at it and what this virus has done in the past, it looks as though it should have some ability to evade immunity. This does not necessarily translate into a greater ability to infect people so we still have things to learn about it, but it is a variant to be watched among many,” said Dr Neuman.

Are there other variants of concern?

“There are hundreds of little branches of the Omicron tree at the moment, and any one of these could go on to be the next big thing. It’s very difficult to predict, in fact we don’t predict, we just watch.

“When there are a crop of new branches coming from one particular place, and they draw a circle around it, and they say that’s a new variant, it gets a name, that’s all,” said Dr Neuman.

Dr. Peter Chin-Hong: Theories on Covid Super Dodgers

What are your theories regarding Covid super dodgers? Are some people simply genetically immune?

“There are several theories – One is genetic. So far, we have an unearthed secret code that makes someone a ‘super dodger,’ that gives them some ‘superpowers.’ We have seen that in other infectious diseases, where some people are more resistant than 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. I think if we find that answer, it will be amazing for Covid because we may be able to make medicines to try to make people more resistant to getting infected.
“The second reason is behavior. Different people in the household being exposed in the ‘same’ way to someone who’s in the household. Some people are just a little bit more averse than others up less close and personal. Maybe, one is the mom of the baby versus the grandparent who is less intimate with the baby.

“It could be that some people are just taking more precautions when they go out. 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 are vaccinated at different times, the further away you are vaccinated, the more vulnerable you are. 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.

“Fourth, is more likely than not people were infected, and they didn’t know it. We know that Covid can cause asymptomatic infection. We know from CDC data, about 60 percent of adults have seen Covid before, and this is before this surge. The likely reason 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, in the world.

“Although the young adults and adolescents may bring the infection into the household, it’s the snotty-nosed kid and the baby that becomes the nucleus to then generate infection within the household because you’re doting on the patient.

“We do know that in Omicron, the proportion of people who are vaccinated is increasing, who are dying, but still the majority are unvaccinated. Of the people who are vaccinated and dying, they tend to be older, like older than 65, and never got a single booster.

“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.

“It’s even more urgent the older you are, so that’s for prevention of serious disease, hospitalization, but if your goal is prevention of infection, it’s not long-lasting but you do have some benefit from topping off your antibodies.

“After the vaccination it lasts for six to eight weeks. It’s not recognizing the new enemy that well, but if you flood the body with non-specific antibodies, it’s still going to be better than if you got vaccinated into a boost since 2021,” said Dr Chin-Hong.

Do you believe that there is severe under account?

“Yes,” said Dr Chin-Hong.

Dr. William Schaffner: People received negative results on their home testing kits even with all the symptoms of Covid. Our home testing kits unable to detect the BA5 variant.

“There may be two reasons for that. The first is that Covid is not the only respiratory virus that’s out there. During summer, we usually do not have many respiratory viruses. There are other respiratory viruses, common cold viruses, virus 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.

“We think that the rapid tests are less apt to give you a positive result in this BA5 era that we are in at the present time.

“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. That’s the important public health problem, it makes people most seriously ill, it occupies hospital beds, it puts a stress on the health care system, and hospitalizations cost much more.
“The distinction between number of cases is important, but hospitalizations is very important,” said Dr Schaffner.

Paxlovid was initially considered a good therapeutic but there are now some concerns, many people cannot take Paxlovid. Could you give us your thoughts on Paxlovid?

“We qualified for Paxlovid and 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 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. Diarrhea can be a side effect of Paxlovid.

“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.

“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. The virus can attach to you, gets inside your cells, and then wishes to multiply and spread further throughout your body. Paxlovid sits on the virus, and tries to prevent it from multiplying.

“Sometimes the virus has just been hiding and when the Paxlovid goes away, it starts to multiply again, and a relatively small proportion of people can have Paxlovid rebound,” said Dr Schaffner.

Are there other therapies in the pipeline that we should be considering?

“There’s a monoclonal antibody that can be given to some people who are eligible for Paxlovid but have a contraindication. There are other therapeutic agents still in the research pipeline,” said Dr Schaffner.

There is a waning of enthusiasm for getting boosted. Many people are saying that they’re going to wait for a better booster that can prevent against BA5 and newer sub-variants, is that a strategy you would suggest? When do you expect to see new formulations becoming available?

“It’s a strategy I would not suggest. It is anticipated that we will have an updated Covid vaccine available sometime this fall. The two major mRNA vaccine manufacturers Moderna and Pfizer predict that they will have at least a bivalent vaccine one that will contain antigens against the original strain plus one of one of the new variant strains, probably BA5.

“Updating the vaccine, the way we update the influenza vaccine each year – that’s anticipated sometime this fall. We don’t have that vaccine in hand, yet.

“The BA5 variant is circulating in every community in this country, so the current recommendations are, if you are eligible for a booster and haven’t received it, receive it this afternoon,” said Dr Schaffner.

Given the predicted surge this fall, would you recommend reinstating mask mandates in all public spaces, especially at schools?

“What the current CDC policy says ‘that will be determined by local public health authorities depending upon the intensity of transmission in that local area,’” said Dr Schaffner.

“California has been very interesting in terms of maybe bringing back or seeing that they may bring back mass mandates under certain circumstances on a generalized level, but there’s very little public appetite, even in liberal California for that.

“Not having a public mask mandate doesn’t mean it’s not a good idea to wear it. It’s still a really strong recommendation, even if you’re maximally boosted or up-to-date on vaccines.

“If you are not up to date on vaccines, that same virus, even though it’s built as mild, can have very serious consequences on you,” said Dr Chin-Hong.

“From a technical standpoint, masks work every time. They’re a really good idea and we should have mask and vaccine mandates,” said Dr Neuman.