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.
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”