Influenza, commonly known as the flu, is a respiratory illness caused by a virus that infects the nose, throat, and sometimes the lungs. While most people recover within a week, the infection can become severe, leading to complications like pneumonia. Medical professionals assess the severity of a flu season or a specific strain based on concrete metrics, including the rates of hospitalization, intensive care unit admissions, and overall mortality. The question of which flu is the “worst” is not constant, as it depends on the virus’s current characteristics and the population’s existing immunity.
Categorizing Influenza A and B
Influenza viruses are primarily categorized into four types: A, B, C, and D. Only types A and B routinely cause the seasonal epidemics that affect humans. Type A is the most concerning category because it can infect multiple species, including humans, birds, and pigs, giving it a vast reservoir for genetic change. This ability to jump species and rapidly acquire new genetic material is why Type A is the only type known to cause global pandemics.
Type B viruses primarily circulate only among humans, limiting their ability to undergo the drastic genetic changes that trigger pandemics. Type B causes serious seasonal flu epidemics and is classified into two main lineages, B/Yamagata and B/Victoria. While Type B can cause significant illness and is often associated with severe outcomes in children, its overall threat is lower than Type A due to its narrower host range and slower mutation rate.
Identifying the Most Virulent Subtypes
The search for the most severe flu strain focuses mainly on Influenza A, which is further classified into subtypes based on two surface proteins: hemagglutinin (H) and neuraminidase (N). There are numerous combinations, but only a few subtypes routinely circulate in humans, most notably A(H1N1) and A(H3N2). These combinations determine the specific virulence of a strain, affecting how easily it spreads and how severely it impacts the body.
Historically, the most virulent seasonal threat is often the A(H3N2) subtype, which has been linked to higher rates of hospitalization and death, particularly among the elderly and very young children. Seasons dominated by H3N2 viruses frequently result in more severe outcomes compared to seasons where H1N1 or Type B are dominant. However, H1N1 can also be associated with severe cases; one study found that hospitalized A(H1N1) patients were more likely to be admitted to the Intensive Care Unit and have higher mortality compared to A(H3N2) patients.
The greatest potential for severity lies in strains that cross from animals to humans, such as avian influenza viruses like H5N1. These zoonotic threats are not currently efficient at human-to-human transmission, but they exhibit extremely high mortality rates in the small number of human cases that do occur. The 1918 “Spanish Flu,” a particularly severe H1N1 strain, serves as a historical example of extreme virulence, demonstrating the devastating potential when a highly pathogenic strain gains the ability to spread easily between people.
Factors Contributing to High Severity
The severity seen in the worst flu strains is often amplified by the host’s biological reaction and the virus’s ability to evade immunity. A major, sudden change in the virus’s surface proteins is known as antigenic shift. This occurs when a new influenza A subtype emerges that is significantly different from previous circulating strains. Since the human population has little existing immunity against this novel strain, it can lead to widespread, severe illness and a pandemic.
A highly virulent strain can also trigger an excessive immune response in the host known as a cytokine storm. Cytokines are signaling molecules that regulate the immune system, but their hyper-production can cause the body to attack its own healthy tissues, leading to severe inflammation and damage in the lungs and other organs. This phenomenon is strongly associated with the severe outcomes and deaths seen in highly pathogenic strains like the 1918 H1N1 and H5N1.
While any flu can be serious, certain populations face a disproportionate risk when a severe strain circulates. The very young, the elderly, and individuals with underlying chronic conditions are consistently the most vulnerable groups. Their immune systems may be less effective at clearing the infection or more prone to complications. However, in specific pandemic cases, such as the 1918 and 2009 H1N1 pandemics, the worst strains disproportionately caused severe illness and death in otherwise healthy young adults.