The Link Between the Flu, Secondary Infections, and Sepsis

By the bioMérieux Connection Editors

As people around the world have gained the ability to more easily travel, viruses have too. A consequence of this viral spread is an increase in critically ill patients, most often throughout flu season, which lasts from October to April in the United States. Critically ill influenza patients may suffer from direct viral invasion or a secondary bacterial infection that arises as a result of infection by the flu virus. These patients are more at risk for complications including pneumonia—severe inflammation of the lungs—and sepsis—the body’s life-threatening response to a severe infection.  

Outbreaks of viral respiratory infection, such as influenza, can lead to a high death toll, often over a short period of time. The is due in part to the mode of viral transmission. Through tiny respiratory droplets in the air, respiratory virus particles can easily travel from one person to another. Globally, upper and lower respiratory infections are the fourth highest cause of mortality. In the U.S., the 2019-2020 flu season was estimated to have caused at least 24,000 deaths and potentially up to 62,000. The 2020-2021 flu season’s toll could be compounded by the COVID-19 pandemic, making infection prevention, diagnosis, and treatment even more critical than in prior years.

Serious influenza can lead to pneumonia, which is severe lung inflammation that occurs in response to an infection, and in which the air sacs fill with pus, making it difficult to breathe. Pneumonia can lead to sepsis and/or death. The link between influenza, pneumonia, and sepsis is complex. But, in patients with severe influenza, pneumonia—and therefore sepsis—is often caused by a secondary bacterial infection.

The association between influenza and bacterial pneumonia became well established following the 1918 flu pandemic. Pneumonia as a consequence of bacterial infection is estimated to have occurred in up to 95% of deaths during that time, and limited options for antibiotics in 1918 made it difficult to treat secondary bacterial sepsis. By the mid-19th century, influenza A and B viruses were both known to predispose patients to bacterial infections. Streptococcus pneumoniaeHaemophilus influenzae, and Staphylococcus aureus are reported as the most common causes of secondary bacterial infection in influenza patients.

Laboratory, clinical, and epidemiological research has emphasized that secondary bacterial infection can significantly increase the morbidity and mortality of viral infections. Up to 75% of patients infected with influenza who go on to acquire pneumonia are confirmed to have a secondary bacterial infection. This, in turn, makes bacterial pneumonia one of the most common causes of sepsis and influenza-associated death. For example, during a 2008 study conducted in the UK, pneumonia was recorded as the most common cause of septic episodes, accounting for the cause of sepsis in 46% of patients. Additionally, during the 2009 H1N1 pandemic, there was an increase in hospitalizations as a result of secondary bacterial pneumonia, which was identified in 29–55% of mortalities.

Viral infections can predispose patients to bacterial infections for many reasons. The conclusion of a 2018 study, researching secondary bacterial infections associated with influenza pandemics, found that, “viral infection aids bacterial infection in a number of ways, including unveiling/providing more sites for adhesion, impairing immune responses and causing cell and tissue destruction allowing for the spread of bacteria and development of invasive infection.”

The severity of a secondary bacterial infection in influenza patients can depend on many factors. These may include the strain of both the bacteria and the virus, and the amount of time between viral infection and bacterial exposure. The amount of time before appropriate treatment is received and the inclusion of antimicrobial stewardship practices throughout a patient’s treatment can also make a difference in clinical outcomes. Studies have shown that almost 30% of patients with severe sepsis are incorrectly diagnosed with pneumonia and that, “this leads to inappropriate initial antibiotic use in the crucial first few days of the septic episode.” Improving diagnostic technology and optimizing its use, combined with good antimicrobial stewardship practices, can aid physicians in making better treatment decisions.

Infection prevention practices can also reduce the incidence of influenza and associated secondary bacterial infections. The best way to do so is to get an annual flu vaccine, in addition to engaging in good hygiene such as regular, thorough hand-washing. The CDC recommends that everyone 6 months and older, with rare exceptions, get a flu vaccine each season by the end of October.


Opinions expressed in this article are not necessarily those of bioMérieux, Inc.

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