Spanish Flu (1918-1920)
The deadliest influenza pandemic in the past century, the Spanish influenza of 1918 to 1920 had an estimated mortality rate of around 2.5 percent (compared to less than 0.1% for previous influenza epidemics) but it killed tens of millions of people because it spread so widely. (Many of those lives could possibly have been saved if anti-flu drugs, antibiotics and mechanical ventilators had existed at that time).
The Spanish flu has been cited as the most devastating epidemic in recorded world history, and is estimated to have killed 50 million people, more than were killed in the first world war. More people died in a single year than from the bubonic plague during the years 1347-1351. It infected 28% of all Americans, and an estimated 675,000 Americans died. Of the U.S. soldiers who died in Europe, half of them fell to disease rather than to the enemy.
This flu was most deadly for people aged 20 to 40, an unusual pattern of morbidity, since influenza is usually a killer of the elderly and young children. Taking into consideration that older people have more natural immunity after years of exposure to a variety of flu viruses, it has been generally believed that cytokine storms might have been responsible for many of the deaths of healthy young adults in this pandemic.
Cytokine Storms
When the immune system is fighting pathogens, cytokines signal immune cells, such as T-cells and macrophages, to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines. Normally, this feedback loop is kept in check by the body. However, in some instances, when the immune system encounters a new and highly pathogenic invader, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. Cytokine storms have the potential to do significant damage to body tissues and organs. If a cytokine storm occurs in the lungs, fluids and immune cells such as macrophages may accumulate and eventually block off the airways.
In 1918, there were reports of people dying within hours of developing symptoms, suggesting a sudden failure of multiple organ systems due to a drastic overreaction of the immune system. In such cases, a healthy immune system could be a liability rather than an asset. It was thought that the strong immune systems of young adults might have been responsible for the disproportionate number of deaths in this age group, whereas the weaker immune systems of children and older adults resulted in fewer deaths. (Human deaths from the bird flu H5N1 also usually involve cytokine storms.)
Bacterial Pneumonia the Probable Culprit
However, two recent research studies of the 1918 pandemic indicate that most deaths were due, not to the influenza virus alone, but to bacterial pneumonia that came on the heels of mostly mild cases of flu, taking advantage of victims’ weakened immune systems. It has long been recognized that most flu deaths are due to pneumonia caused by secondary bacterial infections. In this instance, had a super virus been responsible for most deaths, one might expect people to die fairly rapidly, or at least for most cases to follow a similar progression.
But researchers found that, although (as noted above) some victims succumbed quickly, few people died within three days of showing symptoms, while most lasted more than a week and some survived for two weeks. This pattern indicates death from pneumonia, rather than influenza. The probable role of influenza in this pandemic was to kill cells in the respiratory tract, providing food and a home for opportunistic invading bacteria. In addition, an overstressed immune system makes it easier for the bacteria to obtain a foothold.
Pandemic Severity Index
The Pandemic Severity Index (PSI) is a proposed classification scale developed by the Centers for Disease Control and Prevention (CDC) for reporting the severity of influenza pandemics in the United States. According to the PSI, the 1918 Spanish flu was a category 5 pandemic, (the most deadly category) caused by an unusually severe and deadly influenza A virus strain of subtype H1N1. Indeed, symptoms in 1918 were so unusual that initially this influenza was misdiagnosed as dengue, cholera, or typhoid. One observer wrote, “One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred.” The majority of deaths were from bacterial pneumonia, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lungs. The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands.