Pfizer and BioNTech said Monday that their coronavirus vaccine, already authorized for those 12 and older, has been shown to be safe and effective in young children ages 5 to 11, which potentially provides a pathway toward inoculating the vast majority of U.S. schoolchildren against COVID-19. Ofer Levy, professor of pediatrics at Harvard Medical School and director of the Precision Vaccines Program at Boston Children’s Hospital, sits on a Food and Drug Administration advisory panel for coronavirus vaccines. He spoke with the Gazette about the announcement. This interview was edited for clarity and length.

Q&A

Ofer Levy

Gazette: Was Monday’s announcement an expected event?

Levy: This news is welcome news — I think that’s the word for it. I am a member of the Food and Drug Administration Advisory Committee on the Coronavirus Vaccines and, as you know, they are taking an age de-escalation approach to studying these vaccines. It started with older individuals who are at higher risk of severe COVID and then marched down in age. This highlights that age matters: Children are not little adults. It was the Greek philosopher Heraclitus who said, “The only constant thing in life is change,” and the immune system is no different. From the day we’re born to the day we die, our immune system is changing, so you have to do the study for safety and efficacy. The sponsor in this case, Pfizer, has announced that their data suggests safety and efficacy in kids 5 to 11 years of age. I am just looking at news reports, but they are pointing to a lower dose, maybe a third of the adult dose. I can’t prejudge these data until I see them, but it’s welcome news. The FDA will decide if the data is there to the point that they want to make a decision and whether they will call a meeting of our Vaccines and Related Biological Products Advisory Committee.

Gazette: Would your panel make a recommendation before emergency-use authorization is given?

Levy: It’s at FDA discretion. The FDA holds the deciding authority, and we are advisory to the FDA. The FDA decides whether to convene us, and I would welcome the opportunity, as a pediatrician and somebody who studies precision vaccines.

Gazette: What’s your sense of the need for this vaccine for children at this moment in the pandemic?

Levy: This would be important. We have continued coronavirus transmission in the United States. This pandemic is not over. Kids are getting back to school, and there’s transmission happening between kids, and between children and others. If indeed we have a safe and effective tool to reduce the risk of infection, and possibly transmission and illness from coronavirus in children, that would be a huge win for children and for the rest of society.

Gazette: Do you expect, in the future, for this or another COVID vaccine to be among kids’ routine vaccinations when they’re young. Is that the direction we’re headed?

Levy: The further forward we project, the less certainty there is around the projection. We’d love to reach herd immunity, but it’s possible that we won’t. It’s possible that this becomes an endemic virus that circulates mostly in winter. And then it’s possible that down the line, this becomes part of the pediatric vaccine schedule, but that’s getting quite a bit ahead of ourselves here. We’d like to look at the safety and efficacy for this current study.

Gazette: If the number of kids who get this vaccine mirrors the number of adults who have gotten the adult dose, with low vaccination rates in some areas, is that potentially a problem?

Levy: Any safe and effective vaccine is welcome, and if Americans who couldn’t get vaccinated before now can get vaccinated, that can only be a positive. What will the uptake be? Will it be 10 percent, 50 percent, 90 percent? The higher the uptake, the more benefit we will see as a society, but it would be a win in any case.

Gazette: So even a little bit would be better than what we have now?

Levy: The immediate goal here would be to determine safety and efficacy. If it’s there and the FDA moves forward, then the hope is for a very high percentage of Americans — of all these ages for which there’s an authorized or approved product — to receive the vaccine. That’s how we’re going to make the most headway against the pandemic.

Gazette: How fast could these doses potentially be in kids’ arms?

Levy: I have no insider information here, but from what I’m reading, the FDA might need a month to look at this data. So, let’s say we’re at Oct. 20. If they announce that they want a meeting of the advisory committee, it could be end of October, then a decision by FDA in November and then the CDC by the first, second week of November. So it could be rolling out in mid-to-late November, I’m guessing.

Gazette: So there’s a lot of wiggle room in that process?

Levy: Yes, by plus or minus two weeks.

Gazette: Do you have any message to parents who are reading this news?

Levy: I think they should stay tuned. They should understand that rigorous studies that are placebo controlled are being done in children at different dosing levels to really understand the safety and efficacy of these vaccines in children of younger and younger ages. And they should realize that we do have a robust process at the U.S. Food and Drug Administration to evaluate, in a transparent way, safety and efficacy. We take that seriously. So stay tuned and follow the public guidance.

As the baby boomer generation moves into retirement age, it is expected that by the year 2034, older adults (ages 65 and up) will outnumber children in the United States for the first time in history. As the population ages, demand for health care will increase, and rising rates of alcohol use in older adults may create additional challenges to an already burdened health care system.

Trends in alcohol use in older adults

Alcohol use in older adults has been trending upward over the years, particularly among women. One epidemiologic survey determined that in the United States between 2001 and 2013, among people 65 and older, the rate of alcohol use disorder increased 107 percent. The University of Michigan’s 2021 National Poll on Healthy Aging found that although the majority of older adults surveyed were drinking alcohol at low to moderate levels, there was a subset of older adults exceeding the recommended guidelines for alcohol use. In particular, 20 percent of respondents drank alcohol four or more times per week; 27 percent reported having six or more drinks on at least one occasion in the past year; and 7 percent reported alcohol-related blackouts.

Negative effects of alcohol use in older adults

Drinking too much alcohol can have negative physical and mental health consequences, including heart and liver problems, memory issues, mood disorders, as well as an increased risk of cancer and a weakened immune system. In addition, age-related changes in the body place older adults who drink alcohol at additional risk.

This is an excerpt from an article that appears on the Harvard Health Publishing website.

To read the full story

Dawn E. Sugarman is an assistant professor in the department of psychiatry at Harvard Medical School, and a research psychologist at McLean Hospital in the division of alcohol, drugs, and addiction. Shelly F. Greenfield is a professor of psychiatry at Harvard Medical School, and the Kristine M. Trustey Endowed Chair of Psychiatry at McLean Hospital.

In the next six months, it’s likely that every American will be vaccinated, recovered from coronavirus infection, or both. If that happens, cases and deaths could decline, and the pandemic could start to fade.

That’s what William Hanage predicted in a Thursday evening seminar titled “COVID-19: What we’ve learned about the pandemic and what we keep forgetting.” In his talk, Hanage, an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health and faculty member of the Center for Communicable Disease Dynamics, offered an optimistic outlook, predicting no significant winter surge and a steady drop in cases through March 2022. But, he said, the pandemic will wane only if the country learns from past mistakes, remains cautious, and relies on more interventions than just the vaccine. And, of course, if no new superspreading variant capable of breakthrough infections arises.

“Things could be relatively good, or they could not be,” he said.

Hanage uses both theoretical and laboratory work to track and predict the evolution of various infectious diseases. Since February 2020, he and other epidemiologists have used mathematical modeling to try to anticipate how COVID-19 might spread across the globe. Possible scenarios range from a single, controlled outbreak to an uncontrolled pandemic. Which way the world tips depends on two major factors: how infectious people are before they develop symptoms, and what measures countries use to control outbreaks.

As of February 2020, scientists already knew people carrying the virus were infectious before developing symptoms and that certain now-ubiquitous interventions — social distancing, wearing masks, washing hands — could help prevent the spread.

“It is remarkable how much we’ve forgot — it’s staggering,” Hanage said. “But we’ve also learned a lot.” The problem is, he continued, “Now we know and still do nothing.”

In early 2020, COVID-19-associated mortality correlated with crowding and population density, Hanage said. But by the time record cases and deaths swept through the Sun Belt between September 2020 and February 2021, causing 54 percent of the now nearly 700,000 total deaths in the U.S., those top correlations shifted. Although nursing homes remained the single biggest predictor of mortality, the second biggest was political leaning: Republican-run states, many of which enacted fewer control strategies, experienced the most devastating surges.

Today, those same states still resist the same tactics that might have prevented those surges, said Hanage, citing recent headlines such as the one that ran in Vanity Fair: “Mississippi Governor Announces Bold Plan to Do Nothing to Stop COVID.” As of September, Mississippi has the highest rate of deaths, with about one in every 320 succumbing to the virus.

Even in those same states, Hanage predicts no similar surge in the coming months, perhaps because of immunity built up in the last “grim winter,” he said. That immunity came at a high cost of infection, hospitalization, and death shouldn’t be forgotten.

And, Hanage warned, models — like weather forecasts — can be wrong.

If, for example, vaccination rates plateau at 80 percent, the remaining 20 percent of unvaccinated Americans can still fuel an outbreak as severe as the lethal surges in New York in spring 2020 or the summer 2021 spike in Florida. “The reason for that,” Hanage said of the Florida outbreak, “is the action not taken between then and now.” Even the most vulnerable population members — those 65 and older — still have lower-than-expected vaccination rates. An outbreak in that community could cause a moderate surge in the coming months. “These things really matter when we try to figure out why there are still 2,000 deaths a day,” said Hanage.

As the first speaker in this year’s Microbial Sciences Initiative’s Thursday Seminar Series, Hanage spoke from an on-campus lecture hall to a small, socially distant, in-person audience and a far larger virtual one. He said that vaccination may be the single most important factor to slow the pandemic, but it’s not the only one. Although he is vaccinated, in the on-campus lecture hall Hanage wore a mask, kept the windows open, and didn’t shake hands.

“People want one simple trick to end the pandemic,” he said. “And there isn’t one.” Like the now-famous “Swiss cheese model” of pandemic defense, which Hanage projected on screen, a multilayered defense works best.

Hanage also stressed the importance of wide-scale and rapid testing to help curb outbreaks and identify breakthrough cases in the vaccinated population. Epidemiologists are just now starting to study breakthrough cases and reinfections — two unpredictable factors that could affect how the pandemic shifts over the next six months. That, and it’s still possible a new variant (or “scariant,” Hanage said) could evolve to bypass the immunity afforded by vaccines, making it vital that even vaccinated people remain cautious.

“We cannot direct the wind,” read a quote Hanage projected to conclude his talk, “but we can adjust the sail.”

A Harvard infectious diseases expert says that vaccination rates among the elderly need to be close to 100 percent if another surge of COVID-related hospitalizations and deaths is to be avoided this winter.

Stephen Kissler, a research fellow at the Harvard T.H. Chan School of Public Health, said the strongest factor in COVID severity is the proportion of elderly who are vaccinated. He pointed to Florida, one of the states hardest hit by the summertime delta surge, and the U.K., whose early experience with the variant was not as severe as Florida’s. The difference, Kissler said, appears to be that vaccination rates of the elderly, while relatively high in Florida compared with surrounding states, did not approach U.K. levels.

“Florida was high, but not extremely high,” said Kissler, whose research involves modeling the spread of infectious disease. “Even 5 percent shy of 100 — if 95 percent of those age groups are vaccinated — that remaining 5 percent can still contribute a lot to severe disease and death. We really need near 100 percent vaccination rates in those older age groups.”

More broadly, Kissler expects the summertime surge across the South to shift north as the weather cools and people move inside. Though vaccination rates in some northern states are relatively high, delta is infectious enough that the remaining pool of unvaccinated people, coupled with those whose immunity has waned over time, could fuel a winter surge, he said. On top of that, seasonal effects will boost transmission.

“What I expect is that, especially in places that were largely spared from a major summer surge — so especially the more northern parts of the country — are almost certainly going to see another significant winter wave,” Kissler said.

Those surges, he said, will vary from place to place, depending on local immunity levels, but some regions will be hit hard enough to fill hospitals and force delays in elective surgeries. Communities hit hardest will be those with low vaccination rates that haven’t yet seen a delta surge.

“I do still think this winter will probably see, in some parts of the country, similar scenarios to what we saw in parts of the southeastern U.S. this summer, where in some regions hospitals will be very full, we’ll have to put elective surgeries on hold,” Kissler said. “I think those surges will probably be geographically more isolated, since there are different degrees of immunity across the country, but there are still going to be some communities hit pretty hard this winter. I think that’s something we have to be very clear-eyed about moving forward.”

Kissler, who took questions Wednesday during a media conference call, added that it’s possible that this year’s flu season will be worse than last year’s, when, protected by anti-COVID measures such as masks and distancing, the U.S. largely avoided widespread infection. Easing those practices will create fertile ground for illness, he said, noting the heightened importance of flu shots.

With the winter behind us, COVID-19 is likely to follow the path of the 1918 flu and the 2009 H1N1 flu, Kissler said, becoming a milder seasonal affliction, circulating mainly in winter in a population that is largely vaccinated or previously infected.

“My hope is that once we get through this winter wave, we’ll start to enter into a phase of the pandemic where SARS-CoV-2 is more of a seasonal respiratory virus than this incredibly disruptive pandemic virus that we’ve been dealing with,” Kissler said. “We still have a little work left to do, but my hope is that we’re approaching something that is ever closer to normalcy.”

Many people have been talking about the “COVID 15,” referring to gaining 15 pounds during quarantine. But did people really gain weight? This question intrigued researchers. So they examined patient data from electronic health records. Specifically, they looked at 15 million patients’ weight changes the year prior to the start of the pandemic, and then weight change for one year over the course of the pandemic.

As it turns out, 39 percent of patients gained weight during the pandemic, with weight gain defined as above the normal fluctuation of 2.5 pounds. Approximately 27 percent gained less than 12.5 pounds and about 10 percent gained more than 12.5 pounds, with 2 percent gaining over 27.5 pounds.

The role of stress in weight gain

There was a great deal of stress during the first year of the pandemic, and stress is associated with increased cortisol. Increased cortisol has been associated with increased intake of hyperpalatable foods, which are foods high in salt, fat, or both. There is also evidence that our bodies metabolize food more slowly when under stress. In addition, stress and high cortisol levels are associated with increased belly fat, which puts people at risk for diseases like heart disease and Type 2 diabetes. To add to the list of unhealthy effects of stress on the body, high cortisol levels can reduce lean muscle mass, and this in turn has an impact on your metabolic rate. The less lean muscle mass you have, the lower your metabolic rate and the fewer calories you burn at rest. All of this is a set-up for weight gain and poor health with increased stress.

Not everybody put on pounds during quarantine

Some people respond to stress by not eating. These people ignore their hunger cues, and so some lose weight during times of stress. As it turns out, the electronic health record analysis revealed that 35 percent of patients lost weight during the first year of the pandemic.

This is an excerpt from an article that appears on the Harvard Health Publishing website.

To read the full story

Elizabeth Pegg Frates teaches at Harvard Medical School as well as Harvard Extension School. She currently practices lifestyle medicine through her health and wellness coaching company, Wellness Synergy, LLC.

Excerpted from “Letter to a Young Female Physician: Notes from a Medical Life” by Suzanne Koven, associate professor, Harvard Medical School, and primary care physician and writer in residence, Massachusetts General Hospital.

I knocked shyly on the open door of Albert Blake’s hospital room. All I knew about him was that he was 54 years old and that he had leukemia. As I watched him doze for a few long seconds before knocking again more firmly, I took in his gaunt, ashen face and withered arms and observed that Mr. Blake, as we’d been taught to record in our notes, “appeared older than his stated age.” He opened his eyes, smiled, and nodded toward the chair beside his bed, inviting me to sit down. Suddenly he seemed younger, healthier. I felt as if I were looking at one of those holograms where two images alternate, one shifting into the next, in Mr. Blake’s case: sick/well, patient/person.

I’d been assigned to interview Mr. Blake in the spring of my first year of medical school at Johns Hopkins during a course called Clinical Skills. A few weeks earlier my classmates and I sat excitedly in a lecture hall and each received, courtesy of a pharmaceutical company, a starched white coat and a monogrammed black leather doctor’s bag equipped with an otoscope, an ophthalmoscope, a stethoscope, and a reflex hammer. Once a week we’d put on the coats and carried the bags to the hospital to meet, in groups of four or five, an instructor who taught us how to record patients’ histories and how to use our tools. We walked through the hospital corridors on the way to these sessions hoping that we wouldn’t be mistaken for doctors — and also hoping that we would.

“We walked through the hospital corridors on the way to these sessions hoping that we wouldn’t be mistaken for doctors — and also hoping that we would.”

Long before deciding on a medical career, years before I wanted to be a journalist, I’d aspired to be an actor and my new costume and props made me feel as if I were onstage, a sensation reinforced by the scripts I’d newly memorized, long lists of questions we were supposed to ask our patients: Did they have headaches, double vision, ear pain, bloody noses? Had they been exposed to exotic birds or eaten unpasteurized cheese? Did they have chest pain, and did the pain occur when they took a deep breath, or when they ate or walked? So many questions, all of them as abstract to us as philosophy since we did not yet know which diseases could be transmitted by birds or cheese, or what the symptoms we elicited meant, much less how to treat them.

In the following three years, when we knew more, patients would be chosen for us to interview and examine based on whether they had interesting diseases or dramatic findings on their physical exams. We’d be sent to see the patient with sarcoidosis; listen to the chest of the woman with rhonchi, rattling breath sounds so loud even a novice couldn’t miss her pneumonia; introduce ourselves to the man with Wernicke’s encephalopathy, in which chronic heavy alcohol consumption obliterates short-term memory, then we’d wait five minutes, return to the room, and introduce ourselves again to the patient who would, in that short interval, have forgotten meeting us entirely. In Clinical Skills, though, patients were selected for being … patient. Those who agreed to have medical students practice on them might have dozens troop by to ask the same questions again and again. What brought you into the hospital? When did this symptom begin? Have you ever had anything like this before? What brought you into the hospital? What makes it better or worse? What brought you into the hospital?

Mr. Blake was patient. He was also a natural raconteur who said he didn’t mind passing the hours during his tedious hospitalizations by chatting with students. He’d told his story many, many times. Still, when my turn came to settle into the chair by his bed with my clipboard, Mr. Blake did not stint. What had brought him into the hospital? Well, he said, leaning back on his pillows and drawing a leisurely breath, it was like this: One afternoon about a year earlier he was coaching his 10-year-old grandson’s baseball team. He’d been spending more time with the boy since his mother, Mr. Blake’s daughter, had gotten involved with drugs and acquired a boyfriend who was, in Mr. Blake’s opinion, a stone-cold loser. Anyway, there he was, standing behind home plate, urging one of the kids to keep his eye on the ball, when suddenly he’d felt light-headed. He held on to the chain-link fence to keep from falling and as he looked at his fingers, wrapped tightly through the metal wire, he noticed how pale they were.

And on Mr. Blake went, through the arrival of the ambulance, his grandson running in crying from left field, the first and the second and the third rounds of chemo during which his wife held everyone up as she always had, including the Blakes’ daughter, who, not long after the onset of her father’s illness, had ditched the drugs and the boyfriend and would be coming by to visit shortly with his favorite cookies, though he doubted he’d have enough appetite to eat them.

I transcribed all of this information and a few days later, after my instructor had approved my report, tucked it away for sentimental reasons only, thinking I’d be unlikely ever to look at it again.

Some months afterward, though, I dug through my desk drawers looking for my note about Mr. Blake. I was now at the end of my second year and rotating on the oncology ward, where he had again been admitted. I asked if I might be assigned to help take care of him. Mr. Blake didn’t remember me, and he was sicker than when I’d last seen him, but he greeted me as he had before with a warm smile and an encouraging wave. And he again tolerated my history taking, which remained plodding, though was somewhat more efficient now that I had a better idea of what to ask and so could spare him my slavish recitation of all the questions I’d committed to memory. I asked Mr. Blake how he was feeling, got an update on his treatment, which was not going well, and left the room to copy down his medications, allergies, test results, and other data at the nurses’ station. As a new clinical student, I wasn’t expected to finish my note before leaving for the day and considered myself lucky to have waiting at home a thorough account of the onset of Mr. Blake’s illness that I could easily add to what I’d just recorded.

Tucked into a folder containing papers I’d written in college, I found it. My florid descriptions of Mr. Blake’s pale fingers clutching the chain-link fence, his grandson’s tears, the addicted daughter and her loser boyfriend made me cringe. None of that was important. All that counted now were Mr. Blake’s daily fever charts and lab values, his IV fluids and urine output, his chemotherapy regimen. These were matters of life and death, unlike his story, which, however engagingly Mr. Blake had shared it with me, was irrelevant to his current medical care. I tossed my old note back in the folder with my essays on “Bleak House” and “Mrs. Dalloway,” having concluded that it was, like they were, useless. Then I wrote my new note as if I’d never met Mr. Blake before, as if I’d never heard his story.

Copyright 2021 by Suzanne Koven. Used with permission of the publisher, W.W. Norton & Company, Inc. All rights reserved.

Immune checkpoint inhibitors, which unleash the immune response against tumor cells, have revolutionized cancer treatment; however, the medications aren’t effective in a large number of patients, including those with colorectal cancer.

Now, new research led by investigators at Harvard-affiliated Massachusetts General Hospital and the University of Geneva and published in PNAS provides insights on why some types of colorectal cancer don’t respond to immune checkpoint inhibitors, and offers a strategy to overcome their resistance.

“Colorectal cancer is the second leading cause of cancer-related death in the United States and worldwide,” said senior and co–corresponding author Rakesh K. Jain, director of the E.L. Steele Laboratories for Tumor Biology at MGH and Andrew Werk Cook Professor of Radiation Oncology at Harvard Medical School. “A major cause of mortality in patients with colorectal cancer is the development of liver metastases, which is the spread of cancer to the liver.”

Jain explained that most colorectal cancers that spread to the liver do not respond to immune checkpoint inhibitors. When the team injected colorectal cancer cells under the skin in the hind flanks of mice (the most commonly used method for studying cancer in these animals), the cells responded well to immune checkpoint inhibitors, unlike what happens in patients.

To address this discrepancy, the investigators decided to take an orthotopic approach (meaning “the normal place in the body”) by injecting the cancer cells in the relevant anatomical sites — for example, the colon, where primary colorectal cancer cells grow, and the liver, where they metastasize.

“We found that these colorectal cancer mouse models were profoundly resistant to immune checkpoint inhibitors, similar to what is seen in patients,” said co-corresponding author Dai Fukumura, deputy director of the E.L. Steele Laboratories at MGH and associate professor of radiation oncology at HMS. “Our results highlight how the environment in which cancer cells grow can influence the effectiveness of immunotherapy. Also, and most important, they indicate that these orthotopic cancer models should be used to study resistance to immune checkpoint blockade as observed in patients with colorectal cancer.”

To determine how liver metastases are resistant to immune checkpoint blockade, Jain and his colleagues investigated the composition of immune cells present in liver metastases in mice and compared it with that of colorectal cancer cells injected under the skin.

“We found that liver metastases lacked certain immune cells — called dendritic cells — that are required for the activation of other immune cells known as cytotoxic T lymphocytes, which can kill cancer cells,” said lead author William W. Ho, a research fellow at MGH. “We saw a similar situation in patients — their liver metastases showed a lack of dendritic cells and activated T lymphocytes.”

When the team augmented the number of dendritic cells within liver metastases (by giving mice a growth factor called Flt3L), the treatment led to an increase in cytotoxic T lymphocytes within the tumors and caused the tumors to become sensitive to immune checkpoint inhibitors.

“Our study highlights the importance of orthotopic tumor models in immunotherapy studies and underscores the relevance of dendritic cells for effective immune checkpoint blockade,” said co–corresponding author Mikaël J. Pittet, professor of immunology at U. Geneva. “It also points to the possibility of developing new therapies that could be effective in controlling resistant colorectal cancer. For example, the combination of Flt3L and immune checkpoint inhibitors is an interesting therapeutic option that is worth evaluating in clinical trials.”

Co-authors of the study include MGH investigators Igor L. Gomes-Santos, Shuichi Aoki, Meenal Datta, Kosuke Kawaguchi, Nilesh P. Talele, Sylvie Roberge, Jun Ren, Hao Liu, Ivy X. Chen, Patrik Andersson, Sampurna Chatterjee, Ashwin S. Kumar, Zohreh Amoozgar, Qixian Zhang, Peigen Huang, Mei Rosa Ng, Vikash P. Chauhan, Lei Xu, Dan G. Duda, and Jeffrey W. Clark.

Funding for the study was provided by the National Institutes of Health, the Harvard Ludwig Center, the Advanced Medical Research Foundation, Jane’s Trust, and the ISREC Foundation.

By studying 110 children aged two weeks to 21 years who tested positive for COVID-19 at Massachusetts General Hospital (MGH) or urgent care clinics, researchers confirmed earlier findings that infants, children and adolescents are equally capable of carrying high levels of live, replicating SARS-CoV-2 in their respiratory secretions.

The researchers at Harvard-affiliated MGH and colleagues from Brigham and Women’s Hospital and the Ragon Institute of MGH, MIT and Harvard then showed that these high levels of virus correspond with live, infectious virus, and that levels are highest early in the illness in both symptomatic and asymptomatic children. They found no correlation between the age of the children and the amount of their viral load.

The researchers published additional data on several features of the SARS-CoV-2 virus in children in the Journal of Infectious Diseases.

“There had been the question about whether the high viral load in children correlated with the live virus. We’ve been able to provide a definitive answer that these high viral loads are infectious,” says Lael Yonker, pediatric pulmonologist at MGH and co-first author with Julie Boucau, senior research scientist at MGH and the Ragon Institute.

Reassuringly, they also found that viral load had no correlation to severity of disease in the kids themselves, but concerns remain for them and those around them: “Children can carry the virus and infect other people,” says Yonker.

Students and teachers have returned to classrooms, but many questions remain about the impact of the COVID-19 pandemic on children. Most children are asymptomatic or only mildly symptomatic when they develop COVID-19, giving the misconception that children are less infectious. Studying the virologic features of SARS-CoV-2 in children with COVID-19, and how SARS-CoV-2 infection differs between children and adults, is an essential component for establishing effective public health policies, not only to ensure safety within the school but also for controlling the pandemic, says Yonker.

As COVID-19 variants continue to emerge, infected children are potential “reservoirs” for the evolution of new variants as well as potential spreaders of current variants, she says. “Kids with COVID-19, even if asymptomatic, are infectious and can harbor SARS-CoV-2 variants. Variants could potentially impact both the severity of the disease and the efficacy of vaccines, as we are seeing with the Delta variant. When we cultured the live virus, we found a wide variety of genetic variants,” adds Yonker. “New variants have the potential to be more contagious and also make kids sicker.”

Yonker emphasizes that the group’s findings reinforce the importance of masking for children: “The implications of this study show that masking and other public health measures are needed for everyone — children, adolescents, and adults — to get us out of this pandemic.”

The viral loads of kids in the hospital were no different from those found in hospitalized adults, according to the study. Evidence cited by the Centers for Disease Control and Prevention (CDC) suggests that when compared to adults, children “likely have similar viral loads in their nasopharynx, similar secondary infection rates, and can spread the virus to others.”

Increasing awareness of pediatric COVID-19 and implementing broader testing programs for children are two of Yonker’s aspirations. According to the CDC, the “true incidence of SARS-CoV-2 infection in children is not known due to lack of widespread testing and the prioritization of testing for adults and those with severe illness.”

Yonker adds: “To develop effective public health policies, we need data-driven public health guidance. Kids are an essential component of beating the COVID-19 pandemic, and we must learn more about how they are affected and interact with others.”

Co-senior authors are Jonathan Li, director of the Harvard/Brigham Specialty Virology Laboratory and Amy Barczak, infectious disease specialist at MGH and the Ragon Institute.

We all know that exercise is good for us and that being fit can lower our risk of heart disease and possibly help us to live longer, but what amount and type of physical activity can change a person’s fitness level? New research led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH) and Boston University and published in the European Heart Journal provides some specifics.

The research looked at cardiorespiratory fitness, or the capacity of the heart and lungs to supply oxygen to the body’s muscles during physical activity, in 2,070 participants from the Framingham Heart Study, a long-running multigenerational study designed to identify factors that contribute to cardiovascular disease. Participants underwent tests of physiologic parameters during exercise and wore physical activity trackers for a week at one point, then again nearly eight years later.

In this analysis, investigators found that people who increased their steps per day, participated in a greater amount of moderate-to-vigorous physical activity, or reduced their sedentary time between the two exams showed improvements in distinct aspects of cardiorespiratory fitness throughout exercise sessions, from warm-up to peak exercise to recovery. These findings were largely consistent regardless of participants’ baseline activity level, age, sex, weight, and risk of heart disease.

For each minute of increase in average moderate-to-vigorous physical activity, more than 3 minutes of intermediate cadence walking or 14.6 fewer minutes of sedentary time would be required for the equivalent changes in fitness. Increasing moderate-to-vigorous physical activity by 17 minutes per day, taking an additional 4,312 steps per day (approximately 54 minutes at 80 steps per minute), or reducing 249 minutes of sedentary time per day between the two exams corresponded to a 5 percent higher peak VO2, or peak oxygen uptake.

Researchers also found that individuals with higher than the average number of steps or higher than the average amount of moderate-to-vigorous physical activity among the study participants also had above average peak VO2 values regardless of how much sedentary time they had during the day.

“We conducted this analysis to understand relative effects of changing sedentary activity, low-level physical activity, and moderate-to-vigorous activity on multiple domains of exercise capacity as objectively measured by cardiopulmonary exercise testing,” says senior author Gregory D. Lewis, who is director of the Cardiopulmonary Exercise Testing Laboratory at MGH and medical director of MGH’s Heart Failure and Cardiac Transplantation Program. “The results offer adults equivalents of how much reduction in sedentary time, walking, or moderate-to-vigorous exercise will translate to changes in exercise capacity, which in turn are known to strongly predict long-term health status.”

“The most surprising finding of our study was that individuals with higher-than-average steps per day or moderate-to-vigorous physical activity had higher-than-average fitness levels regardless of how much time they spent sedentary. This would indicate that much of the negative effect that being sedentary has on fitness may be offset by also having higher levels of activity and exercise,” says the study’s first author, Matthew Nayor, the Aram Chobanian Assistant Professor of Medicine in the Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology at Boston University Medical Center.

“Physical activity is a cornerstone for modern cardiovascular disease prevention,” says study co-senior author Ravi Shah, director of Clinical and Translational Research in Cardiology at Vanderbilt. “These results support ongoing efforts to improve activity as a means to improve overall cardiometabolic health.”

Co-authors of the study include Ariel Chernofsky, Nicole L. Spartano, Melissa Tanguay, Jasmine B. Blodgett, Venkatesh L. Murthy, Rajeev Malhotra, Nicholas E. Houstis, Raghava S. Velagaleti, Joanne M. Murabito, Martin G. Larson, and Ramachandran S. Vasan.

The Framingham Heart Study is affiliated with Boston University and supported by the National Heart, Lung and Blood Institute. This work was supported by the National Institutes of Health and the American Heart Association.

In pregnant women who tested positive for SARS-CoV-2, the virus that causes COVID-19, male placentas showed increased immune activation compared with female placentas, according to a new study published in Science Translational Medicine.

The significantly higher levels of certain genes and proteins associated with increased immune activation may help protect male fetuses from becoming infected with SARS-CoV-2 in utero, but the resulting inflammation could pose risks to the fetus and child, notes Andrea Edlow, senior author of the study and maternal-fetal medicine specialist at Harvard-affiliated Massachusetts General Hospital (MGH).

Moreover, pregnant women with COVID-19 transferred significantly less immunity to the virus to male fetuses than to female fetuses, which could affect an infant’s risk for becoming infected with SARS-CoV-2. “The sex of the fetus influenced both the mom’s ability to generate antibodies to COVID-19 and to transfer them to her baby,” says Edlow.

This is the first study to look at sex differences in the transfer of a mother’s antibodies from COVID infection to her fetus, and the first to examine sex differences in the placental response to maternal infection.

Epidemiological studies have shown that male adults, children, and infants have a higher prevalence of COVID-19 infection and develop more severe disease than females. Male fetuses and infants are also more vulnerable to a host of pre- and perinatal exposures compared to female babies, so Edlow and her team sought to examine placentas, maternal blood and cord blood from pregnancies affected by maternal SARS-CoV-2 infection.

The study included 68 pregnant women, of whom 38 became infected with SARS-CoV-2 during their third trimester prior to the development of the COVID vaccine. The remaining 30 subjects were healthy pregnant women who tested negative for SARS-CoV-2 in pregnancy. In both groups, half the fetuses were male and half were female.

In a novel discovery, Edlow and her colleagues showed that, compared with female fetuses, the placentas of male fetuses carried by women with COVID-19 had much higher expression of interferon-stimulated genes (ISGs), which play a key role in shielding fetuses from viral invaders in utero. However, the increased expression of ISGs and downstream production of immune cells called cytokines can also result in an inflammatory intrauterine environment, which has been associated with an increased risk for neurodevelopmental or metabolic disease later in life. “While our study didn’t assess those risks specifically, it raises the importance of following these children and looking at male and female fetuses differently,” says Edlow.

In a second significant finding, Edlow’s team showed that mothers with COVID-19 who have male fetuses make lower levels of antibodies against the virus than mothers with female fetuses; they also transfer fewer antibodies to a male fetus. That suggests that males may be more vulnerable to becoming infected with SARS-CoV-2 in infancy and demonstrates that the sex of the fetus can influence the maternal immune response to the virus, notes Edlow.

Next, Edlow and her co-investigators plan to examine the character of antibodies induced by the COVID-19 vaccine and how those are affected by the timing of the vaccine during pregnancy and of course, fetal sex. “We want to know what happens to the placenta when moms are vaccinated against COVID-19 in each of the three trimesters and how fetal sex affects that response,” says Edlow.

Edlow is an assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School and principal investigator at the Vincent Center for Reproductive Biology at MGH.

Major funding for this study was provided by the National Institutes of Health and the March of Dimes.