Worldwide, the flu results in three million to five million cases of severe illness and 291,000 to 646,000 deaths annually, according to the World Health Organization. But what exactly is a “flu-related death”? How does the flu kill?

The short and morbid answer is that in most cases the body kills itself by trying to heal itself. “Dying from the flu is not like dying from a bullet or a black widow spider bite,” says Amesh Adalja, an infectious disease physician at the Johns Hopkins University Center for Health Security. “The presence of the virus itself isn’t going to be what kills you. An infectious disease always has a complex interaction with its host.”

After entering someone’s body—usually via the eyes, nose or mouth—the influenza virus begins hijacking human cells in the nose and throat to make copies of itself. The overwhelming viral hoard triggers a strong response from the immune system, which sends battalions of white blood cells, antibodies and inflammatory molecules to eliminate the threat. T cells attack and destroy tissue harboring the virus, particularly in the respiratory tract and lungs where the virus tends to take hold. In most healthy adults this process works, and they recover within days or weeks. But sometimes the immune system’s reaction is too strong, destroying so much tissue in the lungs that they can no longer deliver enough oxygen to the blood, resulting in hypoxia and death.

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