Drugs That Trick Older People’s Bodies to Behave Younger Might Boost the Effectiveness of a COVID-19 Vaccine
In our April 23rd editorial for this magazine, we argued that addressing the COVID-19 pandemic requires that we both fight the SARS-CoV-2 virus and fortify the human hosts who are most vulnerable to it.
Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults.
Because people over 70 account for more than 80 percent of reported COVID-19 deaths globally, this means we must do everything possible to protect our elders.
A range of recent studies have suggested that systemic knobs might metaphorically be turned to slow the cellular aging process, making us better able to fight off the many diseases correlated with aging. These types of systemic changes might be used to stem the specific decline in immunity caused by aging and to increases the biological capacity of elderly people to effectively fight viral infection.
But while helping make older people more resilient in the face of a viral infection is critical, that's not the only way geroscience can help in our fight against this deadly pandemic.
As we move toward hopefully developing one or more COVID-19 vaccines, researchers must more fully appreciate the ways in which traditional vaccines can be less effective in older people than in younger ones.
Repeated studies have shown that the flu vaccine, for example, has lower efficacy in older people than in younger ones. Older people tend to develop fewer antibodies after being vaccinated because a subset of their white blood cells, called T cells, have become less responsive over time. Some inflammatory peptides that increase with aging are also preventing the action of those T cells.
This is why there's a distinct possibility that a future COVD-19 vaccine, particularly one utilizing the traditional attenuated virus approach, could be less effective in older people than in younger ones.
Given the extreme urgency of developing vaccines that work well for everyone, we need to make sure that researchers are exploring all of the ways our elders can be best protected. While generating a vaccine that works equally well for people of all ages would be ideal, we can't count on that.
One way to bridge this gap might be to trick the bodies of older people into behaving as if they are younger just at the moment what a vaccine is delivered by giving them pre-immunization boosters.
Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults. Use of the drug for a short time period before flu shot immunization increased the antibody production for the flu and resulted in a 52 percent decrease in the occurrence of severe diseases needing medical help or hospitalization. This short-term pre-immunization intervention can also decrease the severity of serious respiratory tract infections, the deadliest manifestations of COVID-19, by similar magnitude. These patients also had almost half the incidence of the non-COVID-19 coronaviruses associated with the common cold.
The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.
An inexpensive generic drug called metformin similarly targets the decline in immunity and inflammation (and extends health span and lifespan) in animals and has been used for decades to protect against the flu. A recent paper from a hospital in Wuhan, China showed that mortality of elderly COVID-19 diabetic patients on metformin was 25 percent less than that of patients with diabetes but not on metformin.
Another study from the U.S. showed that COVID-19 patients on metformin had a 20 percent decrease in mortality and lower inflammation. The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.
We don't yet know whether rapalogues or metformin could be used as COVID-19 immunization boosters, not least because we don't have those vaccines. But we can and should make sure that all vaccine trials including older subjects also consider offering a subset of those subjects appropriate doses of rapalogues or metformin to explore whether doing so can boost the efficacy of a given vaccine.
If we weren't in the middle of the worst pandemic in a century, we would have more time to test our vaccines slowly and sequentially. In the context of the current crisis, however, testing whether immunization boosters might increase the efficacy of potential COVID-19 vaccines for older adults is at the very least a hypothesis worth exploring.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.
Breakthrough drones deliver breast milk in rural Uruguay
Until three months ago, nurse Leopoldina Castelli used to send bottles of breast milk to nourish babies in the remote areas of Tacuarembó, in northern Uruguay, by way of ambulances or military trucks. That is, if the vehicles were available and the roads were passable, which wasn’t always the case. Now, five days per week, she stands by a runway at the hospital, located in Tacuarembó’s capital, watching a drone take off and disappear from view, carrying the milk to clinics that serve the babies’ families.
The drones can fly as far as 62 miles. Long distances and rough roads are no obstacles. The babies, whose mothers struggle to produce sufficient milk and cannot afford formula, now receive ample supplies for healthy growth. “Today we provided nourishment to a significantly larger number of children, and this is something that deeply moves me,” Castelli says.
About two decades ago, the Tacuarembó hospital established its own milk bank, supported by donations from mothers across Tacuarembó. Over the years, the bank has provided milk to infants immediately after birth. It's helped drive a “significant and sustained” decrease in infant mortality, says the hospital director, Ciro Ferreira.
But these children need breast milk throughout their first six months, if not longer, to prevent malnutrition and other illnesses that are prevalent in rural Tacuarembó. Ground transport isn't quick or reliable enough to meet this goal. It can take several hours, during which the milk may spoil due to a lack of refrigeration.
The battery-powered drones have been the difference-maker. The project to develop them, financed by the UNICEF Innovation Fund, is the first of its kind in Latin America. To Castelli, it's nothing short of a revolution. Tacuarembó Hospital, along with three rural clinics in the most impoverished part of Uruguay, are its leaders.
"This marks the first occasion when the public health system has been directly impacted [by our technology]," says Sebastián Macías, the CEO and co-founder of Cielum, an engineer at the University Republic, which collaborated on the technology with a Uruguayan company called Cielum and a Swiss company, Rigitech.
The drone can achieve a top speed of up to 68 miles per hour, is capable of flying in light rain, and can withstand winds of up to 30 miles per hour at a maximum altitude of 120 meters.
"We have succeeded in embracing the mothers from rural areas who were previously slipping through the cracks of the system," says Ferreira, the hospital director. He envisions an expansion of the service so it can improve health for children in other rural areas.
Nurses load the drone for breast milk delivery.
Sebastián Macías - Cielum
The star aircraft
The drone, which costs approximately $70,000, was specifically designed for the transportation of biological materials. Constructed from carbon fiber, it's three meters wide, two meters long and weighs 42 pounds when fully loaded. Additionally, it is equipped with a ballistic parachute to ensure a safe descent in case the technology fails in midair. Furthermore, it can achieve a top speed of 68 miles per hour, fly in light rain, and withstand winds of 30 miles per hour at a height of 120 meters.
Inside, the drones feature three refrigerated compartments that maintain a stable temperature and adhere to the United Nations’ standards for transporting perishable products. These compartments accommodate four gallons or 6.5 pounds of cargo. According to Macías, that's more than sufficient to carry a week’s worth of milk for one infant on just two flights, or 3.3 pounds of blood samples collected in a rural clinic.
“From an energy perspective, it serves as an efficient mode of transportation and helps reduce the carbon emissions associated with using an ambulance,” said Macías. Plus, the ambulance can remain available in the town.
Macías, who has led software development for the drone, and three other technicians have been trained to operate it. They ensure that the drone stays on course, monitor weather conditions and implement emergency changes when needed. The software displays the in-flight positions of the drones in relation to other aircraft. All agricultural planes in the region receive notification about the drone's flight path, departure and arrival times, and current location.
The future: doubling the drone's reach
Forty-five days after its inaugural flight, the drone is now making five flights per week. It serves two routes: 34 miles to Curtina and 31 miles to Tambores. The drone reaches Curtina in 50 minutes while ambulances take double that time, partly due to the subpar road conditions. Pueblo Ansina, located 40 miles from the state capital, will soon be introduced as the third destination.
Overall, the drone’s schedule is expected to become much busier, with plans to accomplish 20 weekly flights by the end of October and over 30 in 2024. Given the drone’s speed, Macías is contemplating using it to transport cancer medications as well.
“When it comes to using drones to save lives, for us, the sky is not the limit," says Ciro Ferreira, Tacuarembó hospital director.
In future trips to clinics in San Gregorio de Polanco and Caraguatá, the drone will be pushed to the limit. At these locations, a battery change will be necessary, but it's worth it. The route will cover up to 10 rural Tacuarembó clinics plus one hospital outside Tacuarembó, in Rivera, close to the border with Brazil. Currently, because of a shortage of ambulances, the delivery of pasteurized breast milk to Rivera only occurs every 15 days.
“The expansion to Rivera will include 100,000 more inhabitants, doubling the healthcare reach,” said Ferreira, the director of the Tacuarembó Hospital. In itself, Ferreira's hospital serves the medical needs of 500,000 people as one of the largest in Uruguay's interior.
Alejandro Del Estal, an aeronautical engineer at Rigitech, traveled from Europe to Tacuarembó to oversee the construction of the vertiports – the defined areas that can support drones’ take-off and landing – and the first flights. He pointed out that once the flight network between hospitals and rural polyclinics is complete in Uruguay, it will rank among the five most extensive drone routes in the world for any activity, including healthcare and commercial uses.
Cielum is already working on the long-term sustainability of the project. The aim is to have more drones operating in other rural regions in the western and northern parts of the country. The company has received inquiries from Argentina and Colombia, but, as Macías pointed out, they are exercising caution when making commitments. Expansion will depend on the development of each country’s regulations for airspace use.
For Ferreira, the advantages in Uruguay are evident: "This approach enables us to bridge the geographical gap, enhance healthcare accessibility, and reduce the time required for diagnosing and treating rural inhabitants, all without the necessity of them traveling to the hospital,” he says. "When it comes to using drones to save lives, for us, the sky is not the limit."