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Reducing the burden of all-cause mortality after influenza hospitalization will require earlier treatment initiation and improved vaccination rates.

Patients hospitalized with influenza have a high burden of all-cause mortality, particularly after they are discharged from the hospital, according to recent findings published in Clinical Infectious Diseases. 

Influenza causes up to 710,000 hospitalizations and as many as 52,000 deaths in the United States each year, Alissa C. O’Halloran, MSPH, and colleagues wrote. 

“Given that most prior studies have largely focused on in-hospital deaths for patients hospitalized with influenza, it is important for the medical community to know the true burden of influenza on post-hospitalization morbidity and mortality, particularly among adults aged 65 and older,” O’Halloran tells Physician’s Weekly. “In addition to post-discharge mortality, further studies are needed to better understand the impact of an influenza-associated hospitalization on [the] need for rehospitalization or other downstream impacts on health status and well-being.” 

Since the 2010-2011 influenza season, the CDC has collected data on all-cause mortality of people hospitalized with influenza for up to 30 days after their discharge, using the Influenza Hospitalization Surveillance Network. O’Halloran and colleagues paired data from the surveillance network with death certificates to find all patients hospitalized with influenza who died of any cause, either in the hospital or within 30 days after discharge, between the 2010-2011 and 2018-2019 seasons. They calculated all-cause mortality in these patients and described their clinical and demographic information.

Nearly Half of Deaths Occurred After Discharge 

The researchers identified 121,390 laboratory-confirmed cases of influenza that resulted in hospitalization. Overall, 5.5% of patients died. More than three-quarters of these deaths occurred in patients aged 65 and older (76%), and 71% of the patients were White. More than one-third (34%) had at least four underlying medical conditions.

O’Halloran and colleagues reported that nearly half (48%) of patients who died did so after they were discharged from the hospital. The median time from discharge to death was 9 days (range, 3-19 days). However, just 37% of patients who died had their deaths attributed to influenza on their death certificates.

“While this analysis assessed all-cause mortality and not specifically influenza-associated mortality, all the deaths occurred soon after an influenza-associated hospitalization. Some of the deaths were due to causes other than influenza; many deaths likely did have influenza as a contributing factor,” O’Halloran explains.

O’Halloran says the new data can help clinicians find ways to reduce mortality, including improving follow-up care in older adults and those with underlying conditions.

“Medical providers should be aware of the risk for mortality soon after discharge from an influenza-associated hospitalization, particularly among adults aged 65 years and older and those with underlying medical conditions,” O’Halloran says. “Causes of death in patients who died after discharge were more often recorded as being related to chronic underlying conditions like cardiovascular disease rather than acute infections. This may indicate that chronic conditions play a larger role in contributing to all-cause mortality in non-hospitalized settings, but also raises questions about the impact of acute influenza infection on exacerbating pre-existing medical conditions.”

Initiating Treatment Earlier & Improving Vaccination Rates

Furthermore, O’Halloran explains that evidence is mounting that antiviral treatment is underutilized in influenza and has declined in recent years, even among people hospitalized with influenza.

“Antiviral treatment for influenza has been demonstrated to improve outcomes, including in-hospital and post-discharge survival, and the Infectious Diseases Society of America recommends antiviral treatment for patients of all ages hospitalized with influenza. While influenza testing can guide treatment, providers should not wait for test results to initiate antiviral treatment in patients with suspected influenza,” O’Halloran says.

Vaccinations for influenza have also fallen since the COVID-19 pandemic.

“Influenza vaccine is our most important tool to prevent influenza and its complications. Importantly, studies have demonstrated that getting a yearly flu vaccine can reduce the severity of influenza—even among people who get sick despite being vaccinated.”

For this reason, she says, clinicians should recommend an annual influenza vaccine for all people 6 months and older. In patients aged 65 and older, O’Halloran notes several options for vaccination: high-dose influenza vaccine, adjuvant influenza vaccine, or recombinant influenza vaccine.

“Additionally, antiviral treatment is recommended as soon as possible for any patient with suspected or confirmed influenza who is hospitalized, has severe, complicated, or progressive illness, or is at higher risk for flu complications,” O’Halloran told Physician’s Weekly. “Earlier treatment initiation, ideally within 48 hours of symptom onset, provides greater clinical benefit compared with late initiation.”