Skyline Happenings

From Yale Medicine – thanks to Ed M.

This winter, when the usual sneezing, wheezing, coughing, and fevers start up, there will be extra protection for people at high risk from at least one common illness. Respiratory syncytial virus (RSV) causes mild cold symptoms in most people but can lead to hospitalization and even death in older people and babies. But now, two new RSV vaccines aimed at older people and a monoclonal antibody for children up to age 2 could become available as soon as late summer or early fall.

“A lot is changing for RSV,” says Scott Roberts, MD, a Yale Medicine infectious diseases specialist. “There have been attempts to make a vaccine for decades, and they have failed for a variety of reasons.”

One turning point came with the investigation of an RSV protein called “RSV fusion (F)” that provided potent stimulation to the immune system—research that paved the way to clinical trials showing positive results. “Now, it looks as though we may have two vaccines for adults in time for the next RSV season—and there are more potential RSV therapeutics in the pipeline,” Dr. Roberts says.

Older people start to lose immunity as they age—they’re unable to fight off infections, such as RSV, as well as they did when they were younger, explains Dr. Roberts. Plus, the COVID-19 pandemic may have led to several years of lost immunity since RSV wasn’t really circulating during that time. However, by November 2022, RSV was surging in children, and the RSV hospitalization rate for older adults was 10 times higher than usual for that time of year. More people were becoming infected, probably as a result of more in-person, maskless contact, he adds.

In June, the Centers for Disease Control and Prevention (CDC) confirmed the Food and Drug Administration (FDA)’s approval of the two vaccines for older people, specifying that those ages 60 and older “may” get them based on “shared clinical decision-making,” meaning they may receive a single dose based on discussions with their health care provider about whether RSV vaccination is right for them.

In July, the FDA approved another preventive option, a monoclonal antibody called nirsevimab (brand name Beyfortus™). In August, the CDC signed off on the drug for all infants up to 8 months old, born during—or entering—their first RSV season, and for a small group during their second season who are between 8 and 19 months old and at high risk for severe disease (including children who are severely immunocompromised).

Dr. Roberts and Thomas Murray, MD, PhD, a Yale Medicine pediatric infectious diseases specialist, answered questions about the coming options for older adults and kids.

What is RSV, and why is it a threat to some people?

RSV is a common respiratory virus that usually causes mild, cold-like symptoms. It’s a seasonal illness, typically starting in the fall and peaking in the winter. Once a person is infected, the treatment is supportive care, such as over-the-counter medications and maintaining hydration. Most people get better in a week or two.

But when RSV makes its way down into the lungs, causing lower respiratory tract disease (LRTD), it can cause vulnerable people, including those 65 and older, to develop life-threatening complications, such as pneumonia, and make existing conditions, such as asthma, congestive heart failure, and chronic obstructive pulmonary disease (COPD), worse. Each year, this leads to 60,000 and 160,000 RSV hospitalizations in adults 65 and older, and 6,000 to 10,000 deaths.

Babies are susceptible to RSV because their immune systems are not fully formed, adds Dr. Murray. “Their lungs aren’t fully developed. So, if the virus gets into the lungs of really young babies, they can develop respiratory problems and need support, such as supplemental oxygen, to help them breathe.”

In children younger than 5, there are approximately 2.1 million RSV-related outpatient visits a year, 58,000 to 80,000 hospitalizations, and 100 to 300 deaths.

How effective are the RSV vaccines for older adults?

Both vaccines for older adults use traditional platforms—similar to a flu shot (and not to be confused with the mRNA technology introduced by Pfizer-BioNTech and Moderna to prevent COVID-19). The RSV vaccines work by introducing an inactivated RSV protein into the body, where it fuses to host cells and stimulates the immune system to recognize the actual RSV virus if/when it encounters it and help prevent severe disease.

Both vaccines performed well in clinical trials, according to data presented to the FDA. Arexvy™, developed by GSK, was the first to receive FDA approval—in early May—based on data from a trial conducted by the company in the U.S. and internationally. The ongoing trial is following participants through three RSV seasons. In late June, GSK reported an overall efficacy of 82.6% against lower respiratory tract disease during the first season, 77.3% for mid-season, and 67.2% over two seasons. Against severe disease, efficacy was 94.1% during the first season, 84.6% at mid-season, and 78.8% over two seasons.

The second vaccine, called Abrysvo™, from Pfizer, showed an efficacy of almost 89% against LRTD involving at least three symptoms in the first year after vaccination, and 78.6% mid-way through a second season in the data presented to the FDA. LRTD symptoms include new or increased cough, wheezing, sputum (phlegm) production, shortness of breath, and/or tachypnea (abnormally rapid breathing).

While data showed that one vaccination could be protective for at least two seasons, no determination has been made on how frequently the shots should be given.

Will there be an RSV vaccine available for children?

The FDA is considering a vaccine that would be given to pregnant women, who would then pass the protection on to their fetuses.

Abrysvo, Pfizer’s vaccine for older people, was recommended to the FDA for this purpose by its advisory panel in May. If the FDA approves the shot, it would be given to mothers-to-be in their late second or third trimester of pregnancy to help them develop antibodies against RSV that would be passed along to the fetus—and it would continue to provide protection to the baby after delivery.

Clinical trials for the vaccine in this age group showed an 81.8% efficacy in preventing severe respiratory illness within three months after birth and 69.4% in the first six months of life. However, a few of the FDA advisors expressed concern over a slight increase in preterm births among women who got the shot—5.6% in vaccinated women compared to 4.7% in an unvaccinated group. (FDA officials said the difference was not statistically significant.)

What do we know about nirsevimab, the FDA-approved monoclonal antibody for infants and toddlers?

Nirsevimab, which was developed by Sanofi and AstraZeneca, is given in a single injection to the thigh. A Phase 3 clinical trial showed that nirsevimab reduced RSV-triggered lower respiratory tract infections serious enough to require medical care by 76.4% and cut RSV hospitalizations in healthy full-term and near-full-term infants by 76.8%.

The monoclonal antibody works differently than a vaccine. “When you’re injected with a vaccine, it causes your body to produce antibodies to protect you against whatever the vaccine is for,” Dr. Murray says. “The monoclonal antibody bypasses that step. Your body gets—in this case—a single kind of antibody directly injected into the bloodstream so that if you’re infected with that organism, the antibodies will bind to it and help you clear the infection.”

The antibody reduces hospitalization significantly, he adds. “Even if it doesn’t completely prevent disease, it can significantly reduce disease severity. This will be extremely helpful this year, especially after the RSV surge we had last winter,” he says. “And in the trials, there was no difference in adverse effects between the placebo and antibody groups.”

What if you are not an older person or an infant?

If you don’t fall into one of those categories and are otherwise healthy, you probably don’t need a preventive therapy, Dr. Murray explains. “Virtually every child has experienced RSV by the age of 2 and has immunity,” he says.

Older children, teenagers, and most adults have strong immunity from multiple exposures and rarely experience LRTD from RSV. “We want to make things available to the highest-risk patients first,” Dr. Murray says. “We’ll have to wait and see whether or not the vaccines will be approved for people at other ages with chronic underlying illnesses, such as serious heart or lung problems.”

Are there side effects from the vaccines or other concerns?

The CDC advisory panel expressed concerns about the clinical trial data to the point where they changed an initially strong recommendation to get the vaccine, if eligible, to one that says people over 60 “may” get an RSV vaccine based on a shared discussion with their doctors. For some, this may mean a discussion with their pharmacist. (The RSV vaccines will be covered by Medicare Part D and, thus, will be administered in pharmacies in many cases.)

One issue was that a few people in the trials developed Guillain-Barré syndrome in the days following the shot. Guillain-Barré is a rare disorder that causes muscle weakness and sometimes paralysis.

In addition, atrial fibrillation (an arrhythmia that can lead to blood clots in the heart) within 30 days of vaccination was reported in 10 participants who received Arexvy and four participants who received a placebo.

“One could argue that the benefits of these vaccines far outweigh the risks; for instance, the protection afforded against severe RSV disease is greater than the small risk of Guillain-Barré in this situation,” says Dr. Roberts. There will be continued monitoring for Guillain-Barré and other issues once the RSV vaccines become available, he adds.

Another issue was that most of the participants in the clinical trials were in their 60s, so there was little data on other high-risk groups, such as those over age 80.

Should you get the RSV vaccine if you’re eligible?

Both doctors say the benefits of the new vaccines for older adults outweigh the potential harms in cases where RSV could be life-threatening. They recommend them to all eligible older adults, particularly those with underlying health conditions, such as heart or lung disease, or weakened immune systems.

They also suggest that people who are vulnerable or could infect others who are at high risk take additional precautions this fall. Since RSV is spread through contact with contaminated surfaces, that includes washing hands often, keeping hands away from your face, avoiding kissing and other close contact with people who have cold-like symptoms, avoiding close contact with sick people, cleaning frequently touched surfaces, such as doorknobs and mobile devices, and staying home when you are sick. “All of these things will protect against RSV,” Dr. Roberts says.

According to the CDC, RSV vaccines may be given at the same time as other vaccines.

Photographs by September Dawn Bottoms. Article from the NYT

Mr. Kristof is an Opinion columnist reporting from Greenwood, Miss. Ms. Bottoms is a photographer from Oklahoma whose work focuses on mental illness, family and poverty.

This is the third in the series “How America Heals” in which Nicholas Kristof is examining the interwoven crises devastating parts of America and exploring paths to recovery.

It’s not just that life expectancy in Mississippi (71.9) now appears to be a hair shorter than in Bangladesh (72.4). Nor that an infant is some 70 percent more likely to die in the United States than in other wealthy countries.

Nor even that for the first time in probably a century, the likelihood that an American child will live to the age of 20 has dropped.

All that is tragic and infuriating, but to me the most heart-rending symbol of America’s failure in health care is the avoidable amputations that result from poorly managed diabetes.

A medical setting cannot hide the violence of a saw cutting through a leg or muffle the grating noise it makes as it hacks through the tibia or disguise the distinctive charred odor of cauterized blood vessels. That noise of a saw on bone is a rebuke to an American health care system that, as Walter Cronkite reportedly observed, is neither healthy, caring nor a system.

Dr. Raymond Girnys, a surgeon who has amputated countless limbs here in the Mississippi Delta, one of the poorest and least healthy parts of America, told me that he has nightmares of “being chased by amputated legs and toes.”

“It starts from the bottom up,” Dr. Girnys said, explaining how patients arrive with diabetic wounds on the foot that refuse to heal in part because of diminished circulation when blood sugar is not meticulously managed in a person with diabetes. Dr. Girnys initially tries to clean and treat the lesions, but they grow deeper, until he has to remove a toe.

When more wounds develop, he takes off the foot in the hope of saving the rest of the leg. New wounds can force him to amputate the leg below the knee and perhaps, finally, above the knee. After that, Dr. Girnys said, the patient is likely to die within five years.

A toe, foot or leg is cut off by a doctor about 150,000 times a year in America, making the United States a world leader of these amputations.

I’ll be blunt: America’s dismal health care outcomes are a disgrace. They shame us. Partly because of diabetes and other preventable conditions, Americans suffer unnecessarily and often die young. It is unconscionable that newborns in India, Rwanda and Venezuela have a longer life expectancy than Native Americans newborns (65) in the United States. And Native American males have a life expectancy of just 61.5 years — shorter than the overall life expectancy in Haiti.

Sources: National Center for Health Statistics, United Nations Note: Life expectancies are for those born in 2020 for the United States and 2021 internationally. Countries with fewer than 20 million people or where data quality was questionable were excluded.

But there are fixes, and three in particular would make a huge difference: expanding access to medical care; more aggressively addressing behaviors like smoking, overeating and drug abuse; and making larger society-wide steps to boost education and reduce child poverty. One reason to believe that we can do better on health care outcomes is that much of the rest of the world already does.