Who's Most At Risk for a Breakthrough COVID Infection?

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Key Takeaways

  • New research shows that people with cancer and dementia have a higher chance of being hospitalized for a breakthrough infection than people who don't have these conditions.
  • Vaccinated people with pancreatic or liver cancer had the greatest risks of a breakthrough infection while people with thyroid or breast cancer had lower risks.
  • Having multiple chronic health conditions and dementia also increased a person’s odds of developing a breakthrough COVID infection.

Fully vaccinated people can still get infected with COVID—even more than once. As researchers work to figure out why these breakthrough COVID infections happen, they've learned a few things that might make a person more likely to get one.

According to two recent studies by researchers at Case Western Reserve University, vaccinated people with cancer or dementia are among the people at the highest risk of getting a breakthrough case of COVID.

What Is Breakthrough COVID?

Breakthrough infections are COVID-19 cases in fully vaccinated people that happen 14 days or more days after they get their second dose of an mRNA vaccine (or first dose of the Johnson & Johnson vaccine).

Despite a strong level of protection from the vaccines, the shots are not perfect. In fact, the Centers for Disease Control and Prevention (CDC) has stated that even with a safe and effective COVID vaccine, some breakthrough infections are expected.

But the CDC also highlights the importance of vaccinations for significantly reducing the risk of severe illness and death in people who get COVID. Only 0.06% of breakthrough infections require hospitalization among the fully vaccinated. Comparatively, during the Omicron surge, unvaccinated adults who got COVID were hospitalized at four times the rate of people who received a primary vaccine series, and 12 times the rate of those who were boosted.

Who Is Most Likely to Get a Breakthrough COVID Infection?

There are many factors that influence a person’s risk of a breakthrough COVID infection, including their overall health and vaccination status.

Naveed Wagle, MD, a neuro-oncologist and associate professor of translational neurosciences at Saint John’s Cancer Institute told Verywell that since the start of the pandemic, people with chronic health conditions have been a vulnerable population for the virus to target.

However, what hasn't been well understood is why people who have "done all the right things"—for example, wearing masks, social distancing, and getting vaccinated—may still get COVID.

“It is frustrating—especially because families are doing everything," said Wagle. "But we’re still sometimes seeing these breakthrough infections."

The two new Case Western Reserve University studies shed some light on how cancer and dementia may increase a person's risk for a breakthrough COVID infection.

The first study, published in JAMA Oncology, found that people undergoing active treatment for certain types of cancers—such as colorectal and lung cancer—were at a higher risk for breakthrough COVID infections, hospitalization, and death.

The second study, published in the journal Alzheimer’s & Dementia, reported there was an 8.6% to 12.4% risk of breakthrough infections in patients with different types of dementia. But the findings suggest breakthrough cases are more linked to other health conditions people with dementia are likely to have than having dementia itself.

Breakthrough Risk in Vaccinated People With Cancer

In the first study, the researchers looked at medical records of 45,253 vaccinated people with at least one of 12 cancer types from December 2020 to November 2021.

The people with cancer were also more likely to be older, have more chronic health conditions on top of cancer (comorbidities), and have a low socioeconomic status.

The researchers calculated the rate of breakthrough COVID infections, hospitalizations, and death (mortality) and compared them to 591,212 vaccinated people who did not have cancer.

The results showed the number of breakthrough COVID infections increased over time, with significantly more breakthrough cases in the cancer group. By November 2021, there were about 52.1 new cases for every 1,000 people with cancer—compared to people without cancer, which averaged 46.9 breakthrough cases for every 1,000 people.

Among all people with cancer, the researchers calculated a 13.6% breakthrough infection rate. In people who did not have cancer, the breakthrough case rate was 4.9%.

Risk by Cancer Type

The researchers also found that the breakthrough infection risk differed depending on the type of cancer a person had.

For example, the people with the following cancers seemed to be at the highest risk of having a breakthrough infection:

The cancers with the lowest risk for a breakthrough COVID infection were:

After matching the demographics, preexisting health conditions, and vaccine types between the cancer group and the non-cancer group, the researchers also noted the lowest risk of breakthrough infections included people with skin cancer and prostate cancer.

The researchers concluded that their findings showed that cancer itself, as well as its treatments, drove the increased breakthrough infection risk.

Risk by Cancer Treatment

People who had cancer therapy in the past year had a greater risk of breakthrough infections than people who were not seeking active treatment. The risk was higher in people actively seeking medical care for:

For vaccinated people with cancer who tested positive for COVID, the researchers calculated a 31.6% risk of hospitalization and a 6.7% risk of death. People without cancer who had COVID had a 25.9% chance of being hospitalized and a 2.7% chance of dying.

Limitations of the Study

The study has some limitations that people should keep in mind when they're reading about the findings.

The research was observational, which means there could have been variables that were missed that, had they been included, may have affected the results.

This can lead to a problem with bias, as the researchers may have chosen the records with the most complete information or only included the people who could be reached for follow-up.

For example, people could have been left out of the analysis if their records did not include a proof of immunization when in reality, they did get vaccinated and it just wasn't recorded (for example, if they got the shot somewhere outside the healthcare system where their records were kept).

Dementia and Breakthrough COVID Risk

For the second study, the researchers analyzed a large data set to track the rate of breakthrough infections in 262,847 fully vaccinated people with dementia who were 65 years and older. They looked at data collected from December 2020 to August 2021.

People with dementia had a greater risk of COVID breakthrough infection than people without dementia. The risk for breakthrough infections in the group ranged from 8.6% to 12.4%.

The researchers noted that the number of breakthrough infections in people with dementia increased from December 2020 but started to soar after May 2021.

Risk by Dementia Type

The type of dementia also influenced a person’s risk for breakthrough COVID:

There were also certain patient characteristics within each dementia type that the researchers noted could have contributed to their risk; for example, people with vascular dementia were more likely to be African American.

Hospitalization Risk

The risk of hospitalization for a breakthrough COVID case also varied by dementia type:

  • People with vascular dementia had the highest risk for hospitalization at 46.2%
  • People with Alzheimer’s had a 39.5% chance of hospitalization
  • People with mild cognitive impairment showed the lowest hospitalization risk at 30.4%

People with dementia with breakthrough infections were more likely to have other health conditions such as hypertension, type 2 diabetes, heart diseases, and cancers. When researchers matched groups based on comorbidities, they found that people with dementia no longer had a significantly higher risk for breakthrough infections than people without dementia.

The findings suggest the risk of breakthrough infections was because of other health conditions that people with dementia have rather than dementia itself.

Limitations of the Study

While the study had a large sample size, the small number of people who met the criteria for dementia, vaccination, and breakthrough COVID meant that the researchers could not calculate the number of deaths from breakthrough infections in people with dementia. Plus, the research design makes it vulnerable to missing information or errors in a patient's medical records.

Additionally, there may have been a selection bias because the researchers could have picked patients that met the requirements for the study. For this reason, the findings might not apply more broadly to other groups.

Why Are People With Alzheimer's or Cancer at Higher Risk?

The researchers think there are two possible reasons for an increased risk of breakthrough infections in people with Alzheimer's or cancer.

One reason is that some cancer treatments, such as chemotherapy, suppress the immune system, which makes it easier for the virus to slip in undetected and spread through the body before an immune response can be mounted. Even if an immune response is made against the virus, it might be too weak to do much good.

A second reason that Wagle theorized is that while COVID vaccination boosts immunity, a person with cancer (for example) may not develop the same level of immunity as someone who does not have those conditions.

According to Wagle, when these people are vaccinated, "they're less likely to have the robust [immune] memory and response" compared to a person who does not have cancer.

Fortunately, Wagle said there are several treatment options that may help prevent COVID from becoming serious in vulnerable people—and one way is to get a booster as soon as possible.

“We are recommending boosters to all our patients because these groups mount less of an initial response because of immunosuppression," said Wagle. "The boosters help re-drive that and try to bring it up as well."

What This Means For You

Research shows that people with cancer or dementia have higher odds of being hospitalized or dying from a COVID-19 infection.

If you or someone you know has one of the two conditions, getting vaccinated and boosted is crucial. Even if a two-dose vaccine can only provide limited protection in people with compromised immune systems, research shows a booster shot can ramp up the immune response against COVID.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Centers for Disease Control and Prevention. Possibility of COVID-19 illness after vaccination.

  2. Pollock BD, Storlie CB, Tande AJ, Sampathkumar P. Real-world incidence of breakthrough coronavirus disease 2019 hospitalization after vaccination vs natural infection in a large, local, empaneled primary care population using time-to-event analysis. Clinical Infectious Diseases. Published online March 5, 2022;ciac186. doi:10.1093/cid/ciac186

  3. Wang W, Kaelber DC, Xu R, Berger NA. Breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with cancer in the US between December 2020 and November 2021. JAMA Oncology. Published online April 8, 2022. doi:10.1001/jamaoncol.2022.1096

  4. Wang L, Davis PB, Kaelber DC, Xu R. COVID‐19 breakthrough infections and hospitalizations among vaccinated patients with dementia in the United States between December 2020 and August 2021. Alzheimer's & Dementia. Published online April 13, 2022. doi:10.1002/alz.12669

By Jocelyn Solis-Moreira
Jocelyn Solis-Moreira is a journalist specializing in health and science news. She holds a Masters in Psychology concentrating on Behavioral Neuroscience.