The former Secretary of State had been fully vaccinated and had a form of blood cancer that can devastate the immune system.
His case is one health officials designate as a breakthrough case because he was fully vaccinated.
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Powell was 84 years old and immunocompromised -- two big risk factors for breakthrough COVID cases. The former Secretary of State was fully vaccinated, yet he died from the virus.
"We know vaccines are not going to be 100%, so we know there are going to be breakthrough infections, those breakthrough infections are uncommon," said Dr. Michael Angarone, a Northwestern Medicine infectious diseases professor.
Infectious disease doctors said breakthrough hospitalizations and deaths are even more rare. According to the Illinois Department of Public Health, 0.032% of the breakthrough cases in Illinois result in hospitalizations and 0.01% in deaths. Of the state's 679 breakthrough deaths, 51% had underlying conditions and 87% were people over 65.
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In Powell's case, not only was he over 80, but had been diagnosed with a blood cancer called multiple myeloma, which has treatments that can also suppress the immune system.
"His immune system may have been weakened, and he may not have responded well to the vaccine and that put him at risk for getting a breakthrough infection," Dr. Angarone explained.
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The risk is out there as long as the virus continues to circulate.
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Powell's death comes at a time where 82,000 people a day are getting the COVID in the U.S. and 1,500 are dying from it - most of which are unvaccinated.
"If you are vaccinated, your chances of getting infected are eight times less, and chances of getting hospitalized or dying are 25 times less than if you are not vaccinated,' said Dr. Robert Citronberg, infectious disease medical director at Advocate Aurora Health.
Infectious disease doctors said Powell's death should be a reminder that vaccines work best when everyone gets vaccinated. Had more people been protected, Powell's risk would have been much lower.