Despite being fully vaccinated against COVID-19, Colin Powell's age and medical history put him at risk of severe disease and death.
Powell, who was the first Black Secretary of State and chairman of the Joint Chiefs of Staff, died from complications of the virus on Monday, his family said in a statement.
He was 84 years old, severely immunocompromised because he had been treated for multiple myeloma - a cancer of white blood cells in bone marrow - and suffering from Parkinson's disease.
'The main issue is that he had an unlucky confluence that gave him a perfect storm for being at severe risk despite being fully vaccinated,' said Dr Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco.
Doctors say that although Powell's breakthrough infection resulted in his death, cases such as these are quite rare.
They explained to DailyMail.com why his conditions put him at increased risk of death - and why it doesn't mean that COVID-19 vaccines are ineffective.
Colin Powell, the first black Secretary of State, died of COVID-19 complications on Monday, despite being fully vaccinated, at age 84. Pictured: Then-Secretary of State Powell listens to a question during a news conference in Beijing, China, October 2004
Doctors say his age, his battle with multiple myeloma - a type of blood cancer - and Parkinson's contributed to his heightened risk of death. Pictured: Powell, then-Chairman of the Joint Chiefs of Staff, holds a news briefing at the Pentagon, January 1991
'Colin Powell's death illustrates the complex layers of managing COVID-19 risk,' Dr Stuart Ray, a professor of medicine at Johns Hopkins University, told DailyMail.com in an email.
'His death is exceptional, in general, because he was fully vaccinated.
'However, his age and comorbidities remind us that vaccination is never 100 percent protective, and people at special risk (and those around them) are wise to take special precautions that we know to be effective. '
No COVID-19 vaccine prevents every single infection, thus so-called 'breakthrough' cases - in which a fully vaccinated person contracts the virus - are bound to occur, but they rarely result in hospitalization or death.
As of October 12, the Centers for Disease Control and Prevention (CDC) reports 24,717 out of 187 million fully vaccinated people, or 0.013 percent, have been hospitalized.
An even smaller number - 7,178 fully vaccinated people, or 0.003 percent - have died, and 85 percent of those are aged 65 and older.
This means that it is very rare for fully vaccinated people to contract COVID-19 and die, and those who do are mostly elderly.
'As you become older, your ability to mount an immune response is affected just by virtue of their age,' Dr Abhijit Duggal, of the department of critical care at the Cleveland Clinic in Ohio, told DailyMail.com.
However, people suffering from underlying conditions such as cancer are at an elevated risk.
A spokeswoman said Powell had successfully undergone treatment for multiple myeloma in the past.
Patients suffering from hematologic cancers - including related to the bone marrow, and other blood-related tissues like Powell - are at especially high risk.
Hematologic cancer patients' immune systems don't tend to produce antibodies to fight off diseases the way they should be.
What's more, many commonly used treatments for these cancers affects parts of the immune systems, such as B cells, which fight bacteria and viruses.
This also prevents the immune system from being able to mount a full response when a patient gets vaccinated.
Powell was immunocompromised from being treated for multiple myeloma, meaning he didn't likely mount an immune response when he was vaccinated. Studies have shown cancer patients mount less of an immune response to vaccines (left) compared to healthy patients (right)
Older people, like Powell, are also at risk for severe infection due to having less robust
