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What We Know About COVID-19’s Effects on Child and Maternal Health
Posted on by Dr. Francis Collins
There’s been a lot of focus, and rightly so, on why older adults and adults with chronic disease appear to be at increased risk for coronavirus disease 2019 (COVID-19). Not nearly as much seems to be known about children and COVID-19.
For example, why does SARS-CoV-2, the novel coronavirus that causes COVID-19, seem to affect children differently than adults? What is the psychosocial impact of the pandemic on our youngsters? Are kids as infectious as adults?
A lot of interesting research in this area has been published recently. That includes the results of a large study in South Korea in which researchers traced the person-to-person spread of SARS-CoV-2 in the early days of the pandemic. The researchers found children younger than age 10 spread the virus to others much less often than adults do, though the risk is not zero. But children age 10 to 19 were found to be just as infectious as adults. That obviously has consequences for the current debate about opening the schools.
To get some science-based answers to these and other questions, I recently turned to one of the world’s leading child health researchers: Dr. Diana Bianchi, Director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Dr. Bianchi is a pediatrician with expertise in newborn medicine, neonatology, and reproductive genetics. Here’s a condensed transcript of our chat, which took place via videoconference, with Diana linking in from Boston and me from my home in Chevy Chase, MD:
Collins: What is the overall risk of children getting COVID-19? We initially heard they’re at very low risk. [NOTE: Since the recording of this interview, new data has emerged from state health departments that suggest that as much as 10 percent of new cases of COVID-19 occur in children.]
Bianchi: Biological factors certainly play some role. We know that the virus often enters the body via cells in the nasal passage. A recent study showed that, compared to adults, children’s nasal cells have less of the ACE2 receptor, which the virus attaches to and uses to infect cells. In children, the virus probably has less of an opportunity to grab onto cells and get into the upper respiratory tract.
Importantly, social reasons also play a role in that low percentage. Children have largely been socially isolated since March, when many schools shut down. By and large, young kids have been either home or playing in their backyards.
Collins: If kids do get infected with SARS-CoV-2, the virus that causes COVID-19, what kind of symptoms are displayed?
Bianchi: Children tend to be affected mildly. Relatively few children end up in intensive care units. The most common symptoms are: fever, in about 60 percent of children; cough; and a mild respiratory illness. It’s a different clinical presentation. Children seem to be more prone to vomiting, diarrhea, severe abdominal pain, and other gastrointestinal problems.
Collins: Are children as infectious as adults?
Bianchi: We suspect that older kids probably are. A recently published meta-analysis, or systematic review of the medical literature, also found about 20 percent of infected kids are asymptomatic. There are probably a lot of kids out there who can potentially infect others.
Collins: Do you see a path forward here for schools in the fall?
Bianchi: I think the key word is flexibility. We must remain flexible in the months ahead. Children have struggled from being out of school, and it’s not just the educational loss. It’s the whole support system, which includes the opportunity to exercise. It includes the opportunity to have teachers and school staff looking objectively at the kids to see if they are psychologically well.
The closing of schools has also exacerbated disparities. Schools provide meals for many kids in need, and some have had a lot of food insecurity for the past several months. Not to mention kids in homeless situations often don’t have access to the internet and other learning tools. So, on the whole, being in school is better for children than not being there. That’s how most pediatricians see it. However, we don’t want to put children at risk for getting sick.
Collins: Can you say a little bit more about the consequences, particularly for young children, of being away from their usual areas of social interaction? That’s true this summer as well. Camps that normally would be a place where lots of kids would congregate have either been cancelled or are being conducted in a very different way.
Bianchi: Thus far, most of the published information that we have has really been on the infection and the clinical presentations. Ultimately, I think there will be a lot of information about the behavioral and developmental consequences of not being exposed to other children. I think that older children are also really suffering from not having a daily structure, for example, through sports.
For younger children, they need to learn how to socialize. There are advantages to being with your parents. But there are a lot of social skills that need to be learned without them. People talk about the one-eyed babysitter, YouTube. The American Academy of Pediatrics has issued recommendations for limiting screen time. That’s gone out the window. I’ve talked with a lot of my staff members who are struggling with this balance between educating or entertaining their children and having so-called quality time, and the responsibility to do their jobs.
Collins: What about children with disabilities? Are they in a particularly vulnerable place?
Bianchi: Absolutely. Sadly, we don’t hear a lot about children with disabilities as a vulnerable population. Neither do we hear a lot about the consequences of them not receiving needed services. So many children with disabilities rely on people coming into their homes, whether it’s to help with respiratory care or to provide physical or speech therapy. Many of these home visits are on hold during the pandemic, and that can cause serious problems. For example, you can’t suction a trachea remotely. Of course, you can do speech therapy remotely, but that’s not ideal for two reasons. First, face-to-face interactions are still better, and, secondly, disparities can factor into the equation. Not all kids with disabilities have access to the internet or all the right equipment for online learning.
Collins: Tell me a little bit more about a rare form of consequences from COVID-19, this condition called MIS-C, Multi-System Inflammatory Syndrome of Children. I don’t think anybody knew anything about that until just a couple of months ago.
Bianchi: Even though there were published reports of children infected with SARS-CoV-2 in China in January, we didn’t hear until April about this serious new inflammatory condition. Interestingly, none of the children infected with SARS-CoV-2 in China or Japan are reported to have developed MIS-C. It seemed to be something that was on the European side, predominantly the United Kingdom, Italy, and France. And then, starting in April and May, it was seen in New York and the northeastern United States.
The reason it’s of concern is that many of these children are gravely ill. I mentioned that most children have a mild illness, but the 0.5 percent who get the MIS-C are seriously ill. Almost all require admission to the ICU. The scary thing is they can turn on a dime. They present with more of a prolonged fever. They can have very severe abdominal pain. In some cases, children have been thought to have appendicitis, but they don’t. They have serious cardiac issues and go into shock.
The good news is the majority survive. Many require ventilators and blood-pressure support. But they do respond to treatment. They tend to get out of the hospital in about a week. However, in two studies of MIS-C recently published in New England Journal of Medicine, six children died out of 300 children. So that’s what we want to avoid.
Collins: In terms of the cause, there’s something puzzling about MIS-C. It doesn’t seem to be a direct result of the viral infection. It seems to come on somewhat later, almost like there’s some autoimmune response.
Bianchi: Yes, that’s right. MIS-C does tend to occur, on an average, three to four weeks later. The NIH hosted a conference a couple weeks ago where the top immunologists in the world were talking about MIS-C, and everybody has their piece of the elephant in terms of a hypothesis. We don’t really know right now, but it does seem to be associated with some sort of exuberant, post-infectious inflammatory response.
Is it due to the fact that the virus is still hiding somewhere in the body? Is the body reacting to the virus with excessive production of antibodies? We don’t know. That will be determined, hopefully, within weeks or months.
Collins: And I know that your institute is taking a leading role in studying MIS-C.
Bianchi: Yes. Very shortly after the first cases of MIS-C were being described in the United States, you asked me and Gary Gibbons, director of NIH’s National Heart Lung and Blood Institute, to cochair a taskforce to develop a study designed to address MIS-C. Staff at both institutes have been working, in collaboration with NIH’s National Institute of Allergy and Infectious Diseases, to come up with the best possible way to approach this public health problem.
The study consists of a core group of kids who are in the hospital being treated for MIS-C. We’re obtaining biospecimens and are committed to a central platform and data-sharing. There’s an arm of the study that’s looking at long-term issues. These kids have transient coronary artery dilation. They have a myocarditis. They have markers of heart failure. What does that imply long-term for the function of their hearts?
We will also be working with several existing networks to identify markers suggesting that a certain child is at risk. Is it an underlying immune issue, or is it ethnic background? Is it this a European genomic variant? Exactly what should we be concerned about?
Collins: Let me touch on the genomics part of this for a minute, and that requires a brief description. The SARS-CoV-2 novel coronavirus is crowned in spiky proteins that attach to our cells before infecting them. These spike proteins are made of many amino acids, and their precise sequential order can sometimes shift in subtle ways.
Within that sequential order at amino acid 614, a shift has been discovered. The original Chinese isolate, called the D version, had aspartic acid there. It seems the virus that spread from Asia to the U.S. West Coast also has aspartic acid in that position. But the virus that traveled to Italy and then to the East Coast of the U.S. has a glycine there. It’s called the G version.
There’s been a lot of debate about whether this change really matters. More data are starting to appear suggesting that the G version may be more infectious than the D version, although I’ve seen no real evidence of any difference in severity between the two.
Of course, if the change turned out to be playing a role in MIS-C, you would expect not to have seen so many cases on the West Coast. Has anyone looked to see if kids with the D version of the virus ever get MIS-C?
Bianchi: It hasn’t been reported. You could say that maybe we don’t get all the information from China. But we do get it from Japan. In Japan, they’ve had the D version, and they haven’t had MIS-C.
Collins: Let’s talk about expectant mothers. What is the special impact of COVID-19 on them?
Bianchi: Recently, a lot of information has come out about pregnant women and the developing fetus. A recent report from the Centers for Disease Control and Prevention suggested that pregnant women are at a greatly increased risk of hospitalization. However, the report didn’t divide out hospitalizations that would be expected for delivering a baby from hospitalizations related to illness. But the report did show that pregnant women are at a higher risk of needing respiratory support and having serious illness, particularly if there is an underlying chronic condition, such as chronic lung disease, diabetes or hypertension.
Collins: Do we know the risk of the mother transmitting the coronavirus to the fetus?
Bianchi: What we know so far is the risk of transmission from mother to baby appears to be small. Now, that’s based on the fact that available studies seem to suggest that the ACE2 receptor that the virus uses to bind to our cells, is not expressed in third trimester placental tissue. That doesn’t mean it’s not expressed earlier in gestation. The placenta is so dynamic in terms of gene expression.
What we do know is there’s a lot of ACE2 expression in the blood vessels. An interesting recent study showed in the third trimester placenta, the blood vessels had taken a hit. There was actual blood vessel damage. There was evidence of decreased oxygenation in the placenta. We don’t know the long-term consequences for the baby, but the placentas did not look healthy.
Collins: I have a friend whose daughter recently was ready to deliver her baby. As part of preparing for labor, she had a COVID-19 test. To her surprise and dismay, she was positive, even though she had no symptoms. She went ahead with the delivery, but then the baby was separated from her for a time because of a concern about the mother transmitting the virus to her newborn. Is separation widely recommended?
Bianchi: I think most hospitals are softening on this. [NOTE: The American Academy of Pediatrics recently issued revised recommendations about labor and delivery, as well as about breastfeeding, during COVID-19]
In the beginning, hospitals took a hard line. For example, no support people were allowed into the delivery room. So, women were having more home deliveries, which are far more dangerous, or signing up to give birth at hospitals that allowed support people.
Now more hospitals are allowing a support person in the room during delivery. But, in general, they are recommending that the mother and the support person get tested. If they’re negative, everything’s fine. If the support person is positive, he or she’s not allowed to come in. If the mother is positive, the baby is separated, generally, for testing. In many hospitals, mothers are given the option of reuniting with the baby.
There’s also been a general discussion about mothers who test positive breastfeeding. The more conservative recommendation is to pump the milk and allow somebody else to bottle-feed the baby while the mother recovers from the infection. I should also mention a recent meta-analysis in the United Kingdom. It suggested that a cesarean section delivery is not needed because of SARS-CoV-2 positivity alone. It also found there’s no reason for SARS-CoV-2 positive women not to breast feed.
Collins: Well, Diana, thank you so much for sharing your knowledge. If there’s one thing you wanted parents to take away from this conversation, what would that be?
Bianchi: Well, I think it’s natural to be concerned during a pandemic. But I think parents should be generally reassuring to their children. We’ll get through this. However, I would also say that if a parent notices something unusual going on with a child—skin rashes, the so-called blue COVID toes, or a prolonged fever—don’t mess around. Get your child medical attention as soon as possible. Bad things can happen very quickly to children infected with this virus.
For the expectant parents, hopefully, their obstetricians are counseling them about the fact that they are at high risk. I think that women with chronic conditions really need to be proactive. If they’re not feeling well, they need to go to the emergency room. Again, things can happen quickly with this virus.
But the good news is the babies seem to do very well. There’s no evidence of birth defects so far, and very limited evidence, if at all, of vertical transmission. I think they can feel good about their babies. They need to pay attention to themselves.
Collins: Thank you, Diana, for ending on those wise words.
Bianchi: Thanks, Francis.
Links:
Coronavirus (COVID-19) (NIH)
Diana W. Bianchi, MD, Biosketch of the NICHD Director (Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH)
Responding to COVID-19, Director’s Corner, NICHD, June 3, 2020
National Child & Maternal Health Education Program (NICHD)
Pregnancy (NICHD)
Public Health Policies Have Prevented Hundreds of Millions of Coronavirus Infections
Posted on by Dr. Francis Collins
The alarming spread of coronavirus disease 2019 (COVID-19) last winter presented a profound threat to nations around the world. Many government leaders responded by shutting down all non-essential activities, implementing policies that public health officials were hopeful could slow the highly infectious SARS-CoV-2, the novel coronavirus that causes COVID-19.
But the shutdown has come at a heavy cost for the U.S. and global economies. It’s also taken a heavy personal toll on many of us, disrupting our daily routines—getting children off to school, commuting to the office or lab, getting together with friends and family, meeting face to face to plan projects, eating out, going to the gym—and causing lots of uncertainty and frustration.
As difficult as the shutdowns have been, new research shows that without these public health measures, things would have been much, much worse. According to a study published recently in Nature [1], the implementation of containment and mitigation strategies across the globe prevented or delayed about 530 million coronavirus infections across six countries—China, South Korea, Iran, Italy, France, and the United States. Take a moment to absorb that number—530 million. Right now, there are 8.8 million cases documented across the globe.
Estimates of the benefits of anti-contagion policies have drawn from epidemiological models that simulate the spread of COVID-19 in various ways, depending on assumptions built into each model. But models are sophisticated ways of guessing. Back when decisions about staying at home had to be made, no one knew for sure if, or how well, such approaches to limit physical contact would work. What’s more, the only real historical precedent was the 1918 Spanish flu pandemic in a very different, much-less interconnected world.
That made it essential to evaluate the pros and cons of these public health strategies within a society. As many people have rightfully asked: are the health benefits really worth the pain?
Recognizing a pressing need to answer this question, an international team of scientists dropped everything that they were doing to find out. Led by Solomon Hsiang, director of the University of California, Berkeley’s Global Policy Laboratory and Chancellor’s Professor at the Goldman School of Public Policy, a research group of 15 researchers from China, France, South Korea, New Zealand, Singapore, and the United States evaluated 1,717 policies implemented in all six countries between January 2020, when the virus began its global rise, and April 6, 2020.
The team relied on econometric methods that use statistics and math to uncover meaningful patterns hiding in mountains of data. As the name implies, these techniques are used routinely by economists to understand, in a before-and-after way, how certain events affect economic growth.
In this look-back study, scientists compare observations before and after an event they couldn’t control, such as a natural disaster or disease outbreak. In the case of COVID-19, these researchers compared public health datasets in multiple localities (e.g., states or cities) within each of the six countries before and several weeks after lockdowns. For each data sample from a given locality, the time period right before a policy deployment was the experimental “control” for the same locality several weeks after it received one or more shutdown policy “treatments.”
Hsiang and his colleagues measured the effects of all the different policies put into place at local, regional, and national levels. These included travel restrictions, business and school closures, shelter-in-place orders, and other actions that didn’t involve any type of medical treatment for COVID-19.
Because SARS-CoV-2 is a new virus, the researchers knew that early in the pandemic, everyone was susceptible, and the outbreak would grow exponentially. The scientists could then use a statistical method designed to estimate how the daily growth rate of infections changed over time within a location after different combinations of large-scale policies were put into place.
The result? Early in the pandemic, coronavirus infection rates grew 38 percent each day, on average, across the six countries: translating to a two-day doubling time. Applying all policies at once slowed the daily COVID-19 infection rate by 31 percentage points! Policies having the clearest benefit were business closures and lockdowns, whereas travel restrictions and bans on social gatherings had mixed results. Without more data, the analysis can’t specify why, but the way different countries enacted those policies might be one reason.
As we continue to try to understand and thwart this new virus and its damage to so many aspects of our personal and professional lives, these new findings add context, comfort, and guidance about the present circumstances. They tell us that individual sacrifices from staying home and canceled events contributed collectively to a huge, positive impact on the world.
Now, as various communities start cautiously to open up, we should continue to practice social distancing, mask wearing, and handwashing. This is not the time to say that the risk has passed. We are all tired of the virus and its consequences for our personal lives, but the virus doesn’t care. It’s still out there. Stay safe, everyone!
Reference:
[1] The effect of large-scale anti-contagion policies on the COVID-19 pandemic. Hsiang S, Allen D, Annan-Phan S, et al. Nature. 2020 June 8 [published online ahead of print].
Links:
Coronavirus (NIH)
Global Policy Lab: Effect of Anti-Contagion Policies (University of California, Berkeley)
Video: How much have policies to slow COVID-19 worked? (UC Berkeley)
Hsiang Lab (UC Berkeley)
“Global Policy Lab Rallies for COVID-19 Research,” COVID-19 News, Goldman School of Public Policy, June 5, 2020.
COVID-19 Brings Health Disparities Research to the Forefront
Posted on by Dr. Francis Collins
The coronavirus 2019 (COVD-19) pandemic has brought into sharp focus many of the troubling things that we already knew about health disparities in the United States but have failed to address. With the bright light now shining on this important issue, it is time to talk about the role research can play in reducing the disproportionate burden of COVID-19, as well as improving the health of all people in our great nation.
In recent weeks, we’ve seen a growing list of disturbing statistics about how blacks, Hispanics, tribal communities, and some other racial, ethnic, and disadvantaged socioeconomic groups are bearing the brunt of COVID-19. One of the latest studies comes from a research team that analyzed county-by-county data gathered about a month ago. Their findings? The 22 percent of U.S. counties that are disproportionately black accounted for 52 percent of our nation’s COVID-19 cases and 58 percent of COVID-19 deaths. In a paper awaiting peer review, the team, led by Emory University, Atlanta, and amfAR, the Foundation for AIDS Research, Washington, DC., noted that neither the size of the county nor whether it was urban or rural mattered [1].
Recently, I had an opportunity to discuss the disparate burden of COVID-19 with Dr. Eliseo Pérez-Stable, Director of NIH’s National Institute on Minority Health and Health Disparities (NIMHD). Besides leading an institute, Dr. Pérez-Stable is a widely recognized researcher who studies various factors that contribute to health disparities. Our conversation took place via videoconferencing, with him linking in from his home in Washington, D.C., and me from my home in nearby Maryland. Here’s a condensed transcript of our chat:
Collins: Eliseo, you and I recently had a chance to have a pretty intense discussion with the Congressional Black Caucus about health disparities and the COVID-19 pandemic. So, could you start off with a little bit about what populations are being hit hardest?
Pérez-Stable: Collecting data about disease incidence and mortality on the basis of race and ethnicity and other important demographic factors, like socioeconomic status, had really been absent in this pandemic until recently.
Part of that I think is entirely understandable. Hospitals were pressed with a surge of very sick patients, and there was a certain amount of fear and panic in the community. So, people were not completing all these forms that usually get turned in to the health departments and then forwarded to the CDC. If you go back in history, similar things happened in the early 1980s with the HIV epidemic. We weren’t collecting data on race and other sociodemographic variables initially. But, with time, we did complete these data and a picture emerged.
With the COVID-19 pandemic, obviously, the outcomes are much faster, with over 60,000 deaths in just a matter of three months. And we started to see reports, initially out of Connecticut, Milwaukee, Chicago, and New Orleans, that African Americans were dying at a disproportionate rate.
Now, the initial—and I think still the most likely—explanation for this higher mortality relates to two factors. The first is a higher rate of co-morbidities. We know that if you have cardiovascular disease, more than mild obesity, or diabetes, you’re more likely to get severe COVID-19 and potentially die from it. So, we could have just said, “Aha! It’s obvious why this population, and others with higher rates of co-morbidities might be expected to have higher rates of severe disease and higher mortality.”
But there is a second factor that relates to getting infected, for which we have much-less clear data. There was recently a map in The Washington Post showing the distribution of the rate of COVID-19 infections in Washington, D.C., by ward. The highest rates are in the wards that are east of the Anacostia River, which are about 90 percent African American. So, there is an appearance of a correlation between the proportion of African Americans in the community and the rate of Covid-19 infection. Now why could that be?
Collins: Yes, what explains that?
Pérez-Stable: Well, I think crowding is part of it, certainly in this neighborhood. A second option would be multiple families living under one roof.
Collins: So, you can’t exactly practice physical distancing very well in that situation.
Pérez-Stable: Absolutely. You and I can go into our respective rooms, probably have our respective bathrooms, and socially and physically isolate from the rest of the household if need be. Many people can’t do that. They have three generations in one small apartment, all using one bathroom, maybe two bedrooms for six or eight people.
So, we do face different conditions by which one casual infection can lead to much more community transmission. But much information still needs to be ascertained and there does seem to be some regional variance. For example, in Chicago, Milwaukee, and Atlanta, the reports, at least initially, are worse than they are in Connecticut or Florida. Also, New York City, which has been the epicenter of the U.S. for this pandemic, has an increased rate of infections and mortality among Latino-Hispanic populations as well. So, it isn’t isolated to an African-American issue.
Collins: What about access to healthcare?
Pérez-Stable: Again, we can postulate based on a little bit of anecdote and a little bit of data. I’m a general internist by background, and I can see the enormous impact this pandemic has had on healthcare settings.
First, elective ambulatory visits and elective admissions to the hospital have been postponed, delayed, or cancelled. About 90 percent of ambulatory care is occurring through telemedicine or telephone connections, so in-person visits are occurring only for really urgent matters or suspected COVID-19.
If you have health insurance and can use systems, you can probably, through telephone triage with a nurse, get either approval or nonapproval for being tested [for COVID-19], drive to a place, get tested by someone wearing protective equipment, and never actually have to visit with anyone. And you’ll get your result now back as soon as one day, depending on the system. Now, if you’re insured, but don’t really know how to use systems, navigating all these things can be a huge challenge. So, that could be a factor.
People are also afraid to come to clinic, they’re afraid to show up at the emergency room, because they’re afraid to get infected. So, they’re worried about going in, unless they get very sick. And when they get very sick, they may be coming in with more advanced cases [of COVID-19].
So, telephone triage, advice from clinicians on the phone, is critical. We are seeing some doctors base their decisions on whether a person is able to breathe okay on the phone, able to say a whole sentence without catching their breath. These kinds of basic things that we learned in clinical medicine training are coming into play in a big way now, because we just cannot provide the kind of care, even in the best of circumstances, that people may need.
Of course, uninsured patients will have even more barriers, although everyone in the healthcare system is trying their best to help patients when they need to be helped, rather than depend on insurance triage.
Collins: A big part of trying to keep the disease from spreading has been access to testing so that people, even those with mild symptoms, can find out if they have this virus and, if so, quarantine and enable public health workers to check out their contacts. I’m guessing, from what you said, that testing has been happening a lot less in urban communities that are heavily populated by African Americans and that further propagates the spread of the disease. Am I right?
Pérez-Stable: So far, most testing has been conducted on the basis of symptoms. So, if you have enough symptoms that you may potentially need to be hospitalized, then you get tested. Also, if you’re a healthcare worker who had contact with a COVID-19 patient, you might be tested, or if there’s someone you’ve been very close to that was infected, you may be tested. So, I don’t think so much it’s a matter of disproportionate access to testing by one group or another, as much as that the overall triage and selection criteria for testing have been rather narrow. Up until now, it has not been a simple process to get tested for COVID-19. As we scale up and get better point-of-care tests and much easier access to getting tested, I think you’ll see dissemination across the board.
Collins: It’s interesting we’re talking about this, because this is an area that Congress recently came to NIH and said, “We want you to do something about the testing by encouraging more technology, particularly technology that can be distributed to the point-of-care, and that is out in the community.”
Everyone wants a test that gives you a quick turnaround, an answer within an hour, instead of maybe a day or two. A big part of what NIH is trying to do is to make sure that if we’re going to develop these new testing technologies, they get deployed in places that otherwise might not have much access to testing—maybe by working through the community health centers. So, we’re hoping we might be able to make a contribution there.
Pérez-Stable: The economic factors in this pandemic are also huge. A significant proportion of the population that we’re referring to—the disparity population, the minorities, the poor people—work in service jobs where they’re on the front line. They were the restaurant servers and people in the kitchen, they’re still the bus drivers and the Uber drivers, and those who are working in pharmacies and supermarkets.
On the one hand, they are at higher risk for getting infected because they’re in more contact with people. On the other hand, they’re really dependent on this income to maintain their household. So, if they test positive or get exposed to COVID-19, we really do have a challenge when we ask them to quarantine and not go to work. They’re not in a position where they have sick leave, and they may be putting themselves at risk for being laid off.
Collins: Eliseo, you’ve been studying health disparities pretty much your whole research career. You come from a community where health disparities are a reality, having been born in Cuba and being part of the Latino community. Did you expect that COVID-19 would be this dramatic in the ways in which it has so disproportionately affected certain groups?
Pérez-Stable: I can’t say that I did. My first thought as a physician was to ask: “Is there any reason to think that an infectious agent like COVID-19 would disproportionally infect or impact any population?” My gut answer was “No.” Infectious diseases usually seem to affect all people; sort of equal opportunity invaders. There are some data that would say that influenza and pneumonia are not any worse among African Americans or Latinos than among whites. There are some slight differences in some regions, but not much.
Yet I know this a question that NIH-funded scientists are interested in addressing. We need to make sure that there aren’t any particular susceptibility factors, possibly related to genetics or the lung epithelium, that lead to such different COVID-19 outcomes in different individuals. Clearly, something must be going on, but we don’t know what that is. Maybe one of those factors tracks through race or ethnicity because of what those social constructs represent.
I recently listened to a presentation by Rob Califf, former FDA Commissioner, who spoke about how the pandemic has created a spotlight on our disparities-creating system. I think much of the time this disparities-creating system is in the background; it doesn’t really affect most people’s daily lives. Now, we’re suddenly hit with a bucket of cold water called COVID-19, and we’re saying what is going on and what can we do about it to make a difference. I hope that, once we begin to emerge from this acute crisis, we take the opportunity to address these fundamental issues in our society.
Collins: Indeed. Let’s talk about what you’re doing at NIMHD to support research to try to dig into both the causes of health disparities and the interventions that might help.
Pérez-Stable: Prompted by your motivation, we started talking about how minority health and health disparities research could respond to this pandemic. In the short-term, we thought along the lines of how can we communicate mitigation interventions, such as physical distancing, in a more effective way to our communities? We also asked what we could do to enhance access to healthcare for our populations, both to manage chronic conditions and for diagnosis and treatment of acute COVID-19.
We also considered in the mid- and long-term effects of economic disruption—this surge of unemployment, loss of jobs, loss of insurance, loss of income—on people’s health. Worries include excess use of alcohol and other substances, and worsening of mental and emotional well-being, particularly due to severe depression and chronic mental disorders not being well controlled. Intimate partner violence has already been noted to increase in some countries, including France, Spain, and the United States, that have gone on physical distancing interventions. Similarly, child abuse can be exacerbated under these circumstances. Just think of 24/7 togetherness as a test of how people can hold it together all the time. I think that that can bring out some fragility. So, interventions to address these, that really activate our community networks and community-based organizations, are real strengths. They build on the resilience of the community to highlight how we can get through this difficult period of time.
I feel optimistic that science will bring answers, in the form of both therapies and vaccines. But in the meantime, we have a way to go and we a lot to do.
Collins: You mentioned the promise of vaccines. The NIH is working intensively on this, particularly through a partnership called ACTIV, Accelerating Covid-19 Therapeutic Interventions and Vaccines. We hope that in several more months, we’ll be in a position to begin testing these vaccines on a large scale, after having some assurances about their safety and efficacy. From our conversation, it sounds like we should be trying to get early access to those vaccines to people at highest risk, including those in communities with the heaviest burden. But how will that be received? There hasn’t always been an easy relationship between researchers, particularly government researchers, and the African-American community.
Pérez-Stable: I think we have learned from our historical experiences that mistrust of the system is real. To try to pretend that it isn’t there is a big mistake. Address these concerns upfront, obtain support from thought leaders in the community, and really work hard to be inclusive. In addition to vaccines, we need participation in any clinical trials that are coming up for therapeutics.
We also need research on how optimally to communicate this with all the different segments of the population. This includes not just explaining what it means to be eligible for vaccine trials or therapeutic trials, but also discussing the consequences of, say, getting tested, whether it be a viral or antibody test. What does the information mean for them?
Most people just want to know “Am I clear of the virus or not?” That certainly could be part of the answer, but many may require more nuanced responses. Then there’s behavior. If I’m infected and I recover, am I safe to go back out and do things that other people shouldn’t do? We’d love to be able to inform the population about that. But, as you know, we don’t really have the answers to that just yet.
Collins: Good points. How do we make sure, when we’re trying to reach out to populations that have shouldered such a heavy burden, that we’re actually providing information in a fashion that is readily understood?
Pérez-Stable: One thing to keep in mind is the issue of language. About 5 to 10 percent of U.S. adults don’t speak English well. So, we really have to address the language barrier. I also want to highlight the challenge that some tribal nations are facing. Navajo country has had particular challenges with COVID-19 infections in a setting of minimal medical infrastructure. In fact, there are communities that have to go and get their water for the day at a distant site, so they don’t have modern plumbing. How can we recommend frequent hand washing to someone who doesn’t even have running water at home? These are just a few examples of the diversity of our country that need to be addressed as we deal with this pandemic.
Collins: Eliseo, you’ve given us a lot to think about in an obviously very serious situation. Anything you’d like to add?
Pérez-Stable: In analyzing health outcomes, researchers often think about responses related to a metabolic pathway or to a gene or to a response to a particular drug. But as we use the power of science to understand and contain the COVID-19 pandemic, I’d like to re-emphasize the importance of considering race, ethnicity, socioeconomic status, the built environment, the social environment, and systems. Much of the time these factors may only play secondary roles, but, as in all science related to humans, I think they have to be considered. This experience should be a lesson for us to learn more about that.
Collins: Thank you for those wonderful, inspiring words. It was good to have this conversation, Eliseo, because we are the National Institutes of Health, but that has to be health for everybody. With COVID-19, we have an example where that has not turned out to be the case. We need to do everything we can going forward to identify ways to change that.
Reference:
[1] Assessing Differential Impacts of COVID-19 on Black Communities. Millet GA et al. MedRxiv. Preprint posted on May 8, 2020.
Links:
Video: Francis Collins and Eliseo Pérez-Stable on COVID-19 Health Disparities (NIH)
Coronavirus (COVID-19) (NIH)
Director’s Corner (National Institute on Minority Health and Disparities/NIH)
COVID-19 and Racial/Ethnic Disparities. Webb Hooper M, Nápoles AM, Pérez-Stable EJ.JAMA. 2020 May 11.
amfAR Study Shows Disproportionate Impact of COVID-19 on Black Americans, amfAR News Release, May 5, 2020.
Coping with the Collision of Public Health Crises: COVID-19 and Substance Use Disorders
Posted on by Dr. Francis Collins
For the past half-dozen years, I’ve had the privilege of attending the Rx Drug and Heroin Abuse Summit. And I was counting on learning more about this national crisis this April in Nashville, where I was scheduled to take part in a session with Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse. But because of the physical distancing needed to help flatten the deadly curve of the coronavirus-19 (COVID-19) pandemic, it proved to be impossible for anyone to attend in person. Still, the summit did go on for almost three days—virtually!
Dr. Volkow and I took part by sharing a video of a recent conversation we had via videoconference. Since we couldn’t take live questions, we solicited some in advance. Here’s a condensed transcript highlighting portions of our dialogue that focused on the impact of the COVID-19 pandemic on individuals struggling with substance abuse disorders, along with all those who are trying to help them.
VOLKOW: Hello, Francis. Nice to see you, virtually!
COLLINS: Nice to see you too. I’m in my home office here, where I’ve been pretty much for the last three weeks. I’ve been stepping outdoors to occasionally get a breath of fresh air, but trying to live up to all those recommendations about social distancing—or at least physical distancing. I’m trying to keep my social connections going, even if they’re electronic.
I think we’re all feeling this is a time of some stress for us at NIH. We are trying to do everything we can to address this COVID crisis and speed up the process of developing vaccines and therapeutics and all kinds of other things. How are you doing? What’s it like being sequestered back in your home space when you are somebody with so much energy?
VOLKOW: Francis, it’s not easy. I actually am very, very restless. We probably are all experiencing that anxiety of uncertainty, looking at the news and how devastating it is. But I think what makes it easier is if we can do something. Working with everything that we have to try to help others, I think, provides some relief.
COLLINS: Yes, we’re going to talk about that right now. In fact, let’s talk about the way in which this crisis, the global pandemic called COVID-19, is colliding with another public health crisis, which is that of substance use disorder. You recently wrote about this collision in an article in the Annals of Internal Medicine. What does this mean? What are some of the unique challenges that COVID-19 brings to people suffering from addiction?
VOLKOW: I’m glad you are bringing up this point because it’s one of the issues of greatest concern for all of us who are working in the field of substance use disorders. We had not yet been able to contain the epidemic of opioid fatalities, and then we were hit by this tsunami of COVID.
We immediately can recognize the unique challenges of COVID-19 for people having an addiction. Some of these are structural; the healthcare system is not prepared to take care of them. They relate also to stigma and social issues. The concept of social distancing makes such people even more vulnerable because it interferes with many of the support systems that can help them to reach recovery. And, on top of that, drugs themselves negatively influence human physiology, making one more vulnerable to getting infected and more vulnerable to worse outcomes. So that’s why there is tremendous concern about these two epidemics colliding with one another.
COLLINS: How has this influenced treatment delivery for people with substance use disorders, who are counting on that to be able to keep themselves from slipping backward?
VOLKOW: Well, that has been very challenging. We’re hearing from multiple sources that it’s become harder for patients to be able to access treatment. And that relates, for example, to access of medications for opioid use disorders, which are the main strategy—and the most effective one—that we have to prevent people from dying from overdoses.
Some clinics are decreasing the number of patients that they can take care of. The healthcare system is also much less able to initiate persons on buprenorphine. And because of social isolation, if you overdose, the likelihood that someone can rescue you with naloxone is much lower. We don’t yet have statistics on about how that’s influencing fatalities, but we are very concerned.
COLLINS: Nora, you are one of the lead persons for NIH’s Helping to End Addiction Long-term (HEAL) initiative. How has the COVID-19 pandemic affected all the grand research plans that we had put in place as part of our big vision of how NIH could help with the substance use disorder crisis?
VOLKOW: Well, $900 million had recently been deployed on research. That is incredibly meritorious, and some of that research had already started. Unfortunately, it has had to stop almost completely. Why? Because the research that’s relying on the healthcare system, for example, is no longer able to focus on research when they have other clinical needs to meet.
Also, research to bring medication-assisted treatments to prison inmates has stopped. Prisons are not allowing the researchers to go on site because they are closing the doors to outsiders, since they are places at high risk for the spread of COVID-19. Furthermore, some institutional review boards (IRBs) are actually closing, making it impossible to recruit patients for the clinical trials. So, most studies have come to a halt. The issue now is how can we become creative and use virtual technologies to advance some of the goals that we aim to achieve with the HEAL initiative.
COLLINS: Of course, this applies to many other areas of NIH-supported research. Most clinical trials, unless they’re for life-threating conditions, are pretty much in a state of hibernation. We can’t justify having people get out there in ways that might put them at risk of COVID-19. So, yes, it’s a tough time for clinical research all over. And that’s certainly what’s happened with the opioid use disorder problems. Still, I think our teams are really devoted to making sure they make the best of this time, doing things that they can do in terms of planning and setting up data systems.
Meanwhile, bring us up to date on what’s happened as far as the state of the opioid crisis. Are there trends there that we ought to look at for a minute?
VOLKOW: Yes, it’s important to actually keep our eyes on the epidemic, because it’s changing so very rapidly. It’s gone from prescription opioids to heroin to synthetic opioids like fentanyl. And what we have observed ramping up over the past two or three years is an increase in fatalities from the use of psychostimulant drugs.
For example, the number of deaths from methamphetamine has increased five-fold over a period of six years. Similarly, deaths from cocaine are going up. The reality is that people are now dying not just from opioids, but from mixtures of drugs and stimulant drugs, most notably methamphetamine.
COLLINS: So, what can we learn from what we’ve been doing about opioid addiction, and try to apply that to this emerging methamphetamine crisis?
VOLKOW: Unfortunately, we do not have effective medications to treat methamphetamine addiction like we do for opioid use disorders. We also do not have an overdose reversal like we have with naloxone. So, in that respect, it is more challenging.
COLLINS: People sometimes think we’re only focused on trying to treat the problems that we have now. What about prevention? One of the questions we received in our HEAL mailbox was: How can small town communities create an environment where addiction does not take root in the next generation of young people? I’m sure you want to talk about the rewarding power of social interactions, even though right now we’re being somewhat deprived of those, at least face-to-face.
VOLKOW: I’m glad you’re bringing up that question, Francis. Because when you asked at the start of our conversation about how I am doing, I sort of said, “Well, it’s not easy.” But the positive component was that sense that we have a shared mission: we can help others. And the lack of a sense of mission, the lack of a purpose in life, has been identified as one of the factors that make people more vulnerable to take drugs.
Feeling irrelevant, feeling that no one cares for you, is probably one of the most devastating feelings a human being can have. Epidemiological studies show that social isolation and neglect increase dramatically the risk of taking drugs, and, if you are trying to stop taking drugs, it increases that risk of relapse. And so that’s an issue right now of great concern. The challenge is “How do we provide social support for people at risk of substance abuse during the COVID-19 pandemic?”
Also, independent of COVID-19, I think that we as a nation have to face the concept that we have made America vulnerable to drugs because we have eroded that social sense of community. If we are to prevent future generations from getting addicted to drugs, we should build meaningful interactions between people. We should give each individual an opportunity to be part of a society that appreciates them. We do need each other in very, very fundamental ways. We need others for our well-being. If we don’t have that then we become very vulnerable.
COLLINS: Well, here’s one last question from the mailbox. Somebody notes that the “L” in HEAL stands for “long-term.” That is, Helping End Addiction Long-term. The questioner asks: “What’s our vision of a long-term goal and how do we imagine getting there?”
Mine very simply is that we would have an environment that would support people in productive ways, so that the distractions of things that turn out to be destructive are not so tempting, and that the possibility of having meaning in everyone’s life becomes greater.
Ironically, because of COVID-19, we are in the midst of a circumstance where economic distress is pressing on people and social distancing is being required. Seems like we’re going the wrong way. But if you look back in history, often these times of national crisis have been times when people did have the chance to survey what really matters around them, and perhaps to regain a sense of meaning and significance. That’s my maybe slightly over-optimistic view of the current era that we’re in.
Nora, what do you think?
VOLKOW: Francis, I will agree with you. I think that we need to create a society that provides social support and allows people to participate in a meaningful way. If we want to achieve integration of people into society, one of the things that we need to do urgently is remove the stigma of addiction because when you stigmatise someone, you are socially isolating them.
No one likes to be mistreated or discriminated against. So, if you are a person who is addicted and you are afraid of discrimination, you will not seek help. You will continue to isolate. So I think as we’re dealing with the opioid crisis, as we’re dealing with COVID-19, we cannot tolerate discrimination. We cannot tolerate stigma. And we need to be very creative to identify it and to create models that will actually eliminate it.
COLLINS: That’s a wonderful view of where we need to get to. All of these developments give me hope for our capacity to deal with this crisis by working together.
I want to say to all of you who’re listening to this in your own virtual spaces, how much I admire the work that you all are doing, in a selfless way, to try to help our nation deal with what has clearly been a terrible tragedy in far too many lives. I wish you all the best in continuing those creative and energetic efforts, even in the midst of the COVID-19 pandemic. NIH wants to be your ally. We want to be your source of information. We want to be your source of evidence for what works. We want to be your friends.
So, thank you for listening, and thank you, Nora Volkow, for joining me in this discussion today with all of the talent and leadership that you represent. I wish the best health to all of you. Stay safe and keep the progress going!
Links:
Video: Fireside Chat Between NIH, NIDA Heads Addresses COVID-19, the HEAL Initiative, and the Opioids Crisis (National Institute on Drug Abuse/NIH)
COVID-19 Resources (NIDA)
COVID-19: Potential Implications for Individuals with Substance Use Disorders, Nora’s Blog (NIDA)
NIDA Director outlines potential risks to people who smoke and use drugs during COVID-19 pandemic (NIDA)
Collision of the COVID-19 and Addiction Epidemics. Volkow ND. Ann Intern Med. 2 April 2020. [Epub ahead of print]
Helping to End Addiction Long-term (HEAL) Initiative (NIH)
Rx Drug Abuse & Heroin Summit, A 2020 Virtual Experience
Finding New Genetic Mutations Amid Healthy Cells
Posted on by Dr. Francis Collins
You might recall learning in biology class that the cells constantly replicating and dividing in our bodies all carry the same DNA, inherited in equal parts from each parent. But it’s become increasingly clear in recent years that even seemingly healthy tissues contain neighborhoods of cells bearing their own acquired genetic mutations. The question is: What do all those altered cells mean for our health?
With support from a 2018 NIH Director’s New Innovator Award, Po-Ru Loh, Harvard Medical School, Boston, is on a quest to find out, though without the need for sequencing lots of DNA in his own lab. Loh will instead develop ultrasensitive computational tools to pick up on those often-subtle alterations within the vast troves of genomic data already stored in databases around the world.
How is that possible? The math behind it might be complex, but the underlying idea is surprisingly simple. His algorithms look for spots in the genome where a slight imbalance exists in the quantity of DNA inherited from mom versus dad.
Actually, Loh can’t tell from the data which parent provided any snippet of chromosomal DNA. But looking at DNA sequenced from a mixture of many cells, he can infer which stretches of DNA were most likely inherited together from a single parent.
Any slight skew in those quantities point the way to genomic territory where a tiny portion of chromosomal DNA either went missing or became duplicated in some cells. This common occurrence, especially in older adults, leads to a condition called genetic mosaicism, meaning that, contrary to most biology textbooks, all cells aren’t exactly the same.
By detecting those subtle imbalances in the data, Loh can pinpoint small DNA alterations, even when they occur in 1 in 1,000 cells collected from a person’s bloodstream, saliva, or tissues. That’s the kind of sensitivity that most scientists would not have thought possible.
Loh has already begun putting his new computational approach to work, as reported in Nature last year [1]. In DNA data from blood samples of more than 150,000 participants in the United Kingdom Biobank, his method uncovered well over 8,000 mosaic chromosomal alterations.
The study showed that some of those alterations were associated with an increased risk of developing blood cancers. However, it’s important to note that most people with evidence of mosaicism won’t go on to develop cancer. The researchers also made the unexpected discovery that some individuals carried genetic variants that made them more prone than others to pick up new mutations in their blood cells.
What’s especially exciting is Loh’s computational tools now make it possible to search for signs of mosaicism within all the genetic data that’s ever been generated. Even more importantly, these tools will allow Loh and other researchers to ask and answer important questions about the consequences of mosaicism for a wide range of diseases.
Reference:
[1] Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Loh PR, Genovese G, Handsaker RE, Finucane HK, Reshef YA, Palamara PF, Birmann BM, Talkowski ME, Bakhoum SF, McCarroll SA, Price AL. Nature. 2018 Jul;559(7714):350-355.
Links:
Loh Lab (Harvard Medical School, Boston)
Loh Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Institute of Environmental Health Sciences
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