In other cases it is not the flu virus itself that triggers an overwhelming and potentially fatal immune response but rather a secondary infection that takes advantage of a taxed immune system. Typically, bacteria—often a species of Streptococcus or Staphylococcus—infect the lungs. A bacterial infection in the respiratory tract can potentially spread to other parts of the body and the blood, even leading to septic shock: a life-threatening, body-wide, aggressive inflammatory response that damages multiple organs. Based on autopsy studies, Kathleen Sullivan, chief of the Division of Allergy and Immunology at The Children’s Hospital of Philadelphia, estimates about one third of people who die from flu-related causes expire because the virus overwhelms the immune system; another third die from the immune response to secondary bacterial infections, usually in the lungs; and the remaining third perish due to the failure of one or more other organs.

Apart from a bacterial pneumonia, the secondary complications of the flu are numerous and range from the relatively mild, such as sinus and ear infections, to the much more severe, such as inflammation of the heart (myocarditis), brain (encephalitis) or muscles (myositis and rhabdomyolysis). They can also include Reye’s syndrome, a mysterious brain illness that usually begins after a viral infection, and Guillain–Barré syndrome, another virus-triggered ailment in which the immune system attacks the peripheral nervous system. Sometimes Guillain–Barré leads to a period of partial or near-total paralysis, which in turn requires mechanical ventilation to keep a sufferer breathing. These complications are less common, but can be fatal.

The number of people who die from an immune response to the initial viral infection versus a secondary bacterial infection depends, in part, on the viral strain and the cleanliness of the spaces in which the sick are housed. Some studies suggest that during the infamous 1918 global flu pandemic, most people died from subsequent bacterial infections. But more virulent strains such as those that cause avian flu are more likely to overwhelm the immune system on their own. “The hypothesis is that virulent strains trigger a stronger inflammatory response,” Adalja says. “It also depends on the age group getting attacked. During the H1N1 2009 pandemic, the age group mostly affected was young adults, and we saw a lot of primary viral pneumonia.”

In a typical season most flu-related deaths occur among children and the elderly, both of whom are uniquely vulnerable. The immune system is an adaptive network of organs that learns how best to recognize and respond to threats over time. Because the immune systems of children are relatively naive, they may not respond optimally. In contrast the immune systems of the elderly are often weakened by a combination of age and underlying illness. Both the very young and very old may also be less able to tolerate and recover from the immune system’s self-attack. Apart from children between six and 59 months and individuals older than 65 years, those at the greatest risk of developing potentially fatal complications are pregnant women, health care workers and people with certain chronic medical conditions, such as HIV/AIDS, asthma, and heart or lung diseases, according to the World Health Organization.