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What to know about your risk of a serious or fatal breakthrough COVID infection

Houston Fire Department paramedics prepare to transport a COVID-19 positive woman to a hospital on September 15, 2021 in Houston, Texas. The area continues to see large number of COVID-19 hospitalizations.
Houston Fire Department paramedics prepare to transport a COVID-19 positive woman to a hospital on September 15, 2021 in Houston, Texas. The area continues to see large number of COVID-19 hospitalizations.

When Colin Powell died this week from complications related to COVID-19, it was a shock to many Americans.

Though scientists and federal health officials are adamant that the vaccines work well to protect against hospitalization and death, it's unnerving to hear of fully vaccinated people like Powell, or perhaps your own friends and neighbors, falling severely ill with COVID-19.

So how well do the vaccines work? How serious is the risk of a serious breakthrough infection, one that could land you in the hospital?

In Powell's case, of course, there are several reasons he was at higher risk. He was 84 and had been treated in recent years for multiple myeloma — a blood cancer that forms in plasma cells, which are critical for the immune system. These facts alone would put him at very high risk for a breakthrough illness, says Dr. Rachel Bender Ignacio, who directs COVID-19 clinical research at the Fred Hutchinson Cancer Research Center.

"We shouldn't change our risk estimation on one good or bad outcome that happens to a single person," she says. "The vaccines are still holding up extremely well."

Even with concerns about the possibility of waning protection from the vaccine, scientists say the best data in the U.S. still tell a clear story: people who are fully vaccinated have a far lower risk of getting infected or dying from COVID-19 than the unvaccinated, according to data representing about 30% of the U.S. population from the Centers for Disease Control and Prevention.

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Who is getting severely ill from COVID after being vaccinated?

Those who do have severe breakthrough illnesses tend to be older or have serious underlying health conditions, or a combination of those risk factors.

"People who are of advanced age or who have impaired immune systems always respond less well to vaccines — that's true whether it's flu vaccine or really any other vaccine," says Bender Ignacio.

The effect of age on the risk of breakthrough infections is stark. The CDC released data separating breakthrough infections and deaths by age. Among fully vaccinated people, those aged 80 or older had a almost 13 times greater risk of dying from COVID than people of all ages. However unvaccinated people in their 80s were at far greater risk than vaccinated ones.

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Research shows that people who fare the worst tend to be especially medically fragile. A study of vaccinated patients hospitalized at the Yale New Haven Health System found that the median age was about 80 and many had underlying problems, including cardiovascular disease, lung disease, diabetes and some were also on immunosuppressive drugs.

While those findings came before the surge of the delta variant, Dr. Hyung Chun, who led the study, says their ongoing research shows these types of patients still account for most breakthrough illnesses "even with the shifting landscape of breakthrough infections."

Chun says those who are vaccinated generally tend to do better once they are in the hospital, compared to those who aren't vaccinated.

"Even if you were hospitalized [with a breakthrough infection], the trend we've been observing is that you will likely be far less sick in terms of needing things like supplementary oxygen or mechanical ventilation, or even your risk of death," says Chun, an associate professor of cardiology at the Yale School of Medicine.

As of mid July, the CDC found that people who were immunocompromised accounted for 44% of breakthrough hospitalizations — a figure that supported the decision to recommend a third shot of the vaccine to people who met the criteria of having a weakened immune system. A more recent study conducted by the vaccine maker Pfizer and not yet peer reviewed, found that study participants who were immunocompromised accounted for about 60% of the breakthrough hospitalizations and were three times more likely to have an infection compared to people who weren't immunocompromised.

The three major clinical trials done by the vaccine makers did not include immunocompromised people, so researchers are still trying to tease apart how different medical conditions affect a person's immune response to the vaccine, says Dr. Jonathan Golob, an assistant professor at the University of Michigan in the Division of Infectious Diseases.

"The vaccines are still stellar, including against delta for just about everyone, except for people with very, very impaired immune systems," he says. That list includes patients who've had an organ transplant, with active cancer, or some other severe autoimmune disease that requires a lot of medicine to treat it. "All those people, I would say, still need to be cautious and the best thing to protect them is to have everyone around them vaccinated," he says.

How common is it to have a severe breakthrough illness?

It's currently hard to answer that in the U.S. To date, 7,178 people are reported to have died from COVID-19 after being vaccinated and about 85% were 65 and older, according to the CDC, but these figures are meant to be a "snapshot" and are an undercount, an agency spokesperson told NPR. In that same time period, approximately 190 million have been fully vaccinated in the U.S.

As more Americans get vaccinated, the raw numbers of serious breakthrough infections will inevitably increase as long as the virus is spreading, but those figures can be misleading.

"Hospitalizations due to breakthrough infection are higher than even a few months ago, but this should be viewed in light of the fact that more people are fully vaccinated," says Chun. "You're working with a much bigger denominator of patients."

Bottom line: The risks of hospitalization are far greater for the unvaccinated. The chance of being hospitalized in the U.S. for COVID-19 is 12 times higher if you are unvaccinated, according to recent CDC data. These rates may vary week to week, the agency notes. And they vary by age group. Unvaccinated adults aged 18-49 were 14 times more likely to be hospitalized, while those over 65 were 9 times more likely.

Some of the most compelling data also comes directly from what hospitals are seeing in their communities.

A study of hospitalized COVID-19 patients at Beaumont Health — Michigan's largest hospital system — found a "dramatic" difference in hospital visits between the vaccinated and unvaccinated, says Dr. Amit Bahl, an emergency physician who authored the study.

"If you were fully vaccinated, you had a 96% reduction in the chance of being hospitalized or going to the emergency room," he says. "A bad outcome for a patient that's fully vaccinated was exceedingly rare."

Some states that track breakthrough hospitalizations are finding a similar pattern.

For example, New York's data shows that 0.06% of the vaccinated population has ended up in the hospital for COVID-19. Minnesota has a similar rate.

However, it's still hard to quantify how often a breakthrough infection leads to someone being hospitalized, because the U.S. is not tracking this data closely on a national level, says Angela Rasmussen, a virologist at the University of Saskatchewan.

"I don't think we're there yet," she says. "We don't really know the denominator — how many breakthrough infections there have been overall."

Has the chance of getting very sick increased and is that why the government is starting to roll out boosters?

The push for booster shots reflects the concern that certain groups of Americans — namely those who are older — appear to be now slightly less protected against a severe case of COVID-19 than they were in the spring, and worries that the risk of infections has risen because of the delta variant. The data vary between the vaccines. The one shot Johnson & Johnson vaccine appears to be the least effective against hospitalization.

But scientists are still trying to untangle exactly what's behind this increased risk.

Older Americans were already more susceptible to the virus. They were also some of the first groups to get vaccinated. "So we have not only a higher risk population, but now a longer time since they received the vaccine," says Bender Ignacio. "And this is exactly why boosters have been recommended for those populations."

The arrival of the delta variant and a surge in cases among the unvaccinated has put many more people in contact with the virus, including people who may be especially vulnerable, says Rasmussen.

"Unfortunately, even though we have a lot more people getting vaccinated, it's still not enough and we still have a lot of virus around," she says. "When those two conditions are met, you're just going to have more breakthrough cases."

Ultimately, the protection against hospitalization — while it may be waning for some groups — doesn't appear to have translated into a major spike of severely sick vaccinated patients, even as the country has dealt with a huge surge in cases.

"Everyone I've seen this week who is critically ill from COVID is unvaccinated," says Golob of the University of Michigan health care system.

Copyright 2021 NPR. To see more, visit https://www.npr.org.