CHEST Physician

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

A version of this article first appeared on WebMd.com.

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

A version of this article first appeared on WebMd.com.

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

A version of this article first appeared on WebMd.com.

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

A version of this article first appeared on WebMD.com.

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

A version of this article first appeared on WebMD.com.

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

A version of this article first appeared on WebMD.com.

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

A version of this article first appeared on WebMD.com.

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

A version of this article first appeared on WebMD.com.

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

A version of this article first appeared on WebMD.com.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

A version of this article first appeared on WebMD.com.

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

A version of this article first appeared on WebMD.com.

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

A version of this article first appeared on WebMD.com.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

A version of this article first appeared on WebMD.com.

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.