This study suggests that over a period of four years, influenza A was associated with a greater number of hospital admissions as compared to influenza B. This is indicative of a greater prevalence of circulating influenza A viruses circulating in the community during the seasons in the study period, as has also been suggested by previous studies [15, 16]. Influenza B infection, however, was more prevalent in younger population but clinical outcomes measured in terms of LOS, ICU admissions, in-hospital mortality, 30-day mortality and unplanned hospital readmissions were comparable to influenza A.
The results of our study are similar to a study by Cohen et al [17] in Israel, who included 454 hospitalised influenza patients with a mean age 66 years over a period of 3 years and found minor epidemiological differences but similar clinical severity and outcomes between influenza A and B viral infections. However, the prevalence of influenza B infection was much higher 32.5% in their study as compared to 11.7% in our study. The prevalence rates of different influenza strains in our study are, however, similar to a report by the influenza complications alert network (FluCAN) [15], which reports annual flu data in 22 sentinel hospitals across Australia, and in 2018 found that among 769 hospitalised patients, influenza B constituted 13% of the total influenza burden. A meta-analysis [18] of studies conducted in Latin America and the Caribbean, between 1999 to 2008 suggests that overall influenza A is more common than influenza B, although there were a few years in a few countries where there was a high percentage of influenza B positive cases than influenza A. The differences in the prevalence of flu strains could be related to varying circulation of the two influenza viruses during different seasons [19]. In our study, we found that the prevalence of influenza B among hospitalised patients has varied from 4.9–25.1% from 2016 to 2019.
The prevalence rate of influenza B in our study is lower than another Australian study [20], which studied epidemiology of all laboratory confirmed influenza B infections for inpatients and outpatients across Australia between 2001–2014 influenza seasons and found that the prevalence of influenza B was 17.1% compared to 11.7% in our study. This slight difference in reporting might be related to the sampling characteristics, because our study included only hospitalised patients compared to inclusion of all influenza cases in their study. In addition, these differences could be related to the under representation of influenza B among hospitalised patients, because, influenza B is more common in younger patients who often have fewer co-morbidities and thus are less likely to present to hospital for exacerbation of chronic medical issues. The other reason for difference in prevalence rates of influenza viruses could be related to the seasonal variation in circulating influenza strains, as our reporting period was from 2016–2020 compared to 2001–2014 in the other study. In addition, it is possible that hospitalisation for flu is determined by the co-morbidities rather than the type of virus with people who are older with multiple comorbidities more likely to be admitted than younger patients with no or fewer medical issues.
The mean age of our study population was 66.5 years which is much older than a previous Australian study [21] in 2015, which included 436 adult hospitalised influenza patients who had a mean age of 54.3 years. This difference in age is likely related to the higher prevalence of influenza B (59.3%) in this other study compared to our population (11.7%). Influenza B is more prevalent in younger population and was the dominant strain in Australia in 2015. Similar to previous studies [20, 22], our study also confirms that influenza B is more prevalent in young adults while influenza A is more common in older hospitalised patients.
In this study, the patient characteristics and background morbidity were similar between influenza A and B, apart from differences in smoking status and history of IHD, which were significantly higher among patients who had influenza A. These findings are similar to a recent study by Cohen et al [17], who included 759 hospitalised influenza patients and found only minor epidemiological differences between the two influenza types but noted a higher prevalence of IHD among influenza A patients. Despite high prevalence of IHD, we did not observe any significant differences in the incidence of ACS (3.2% vs. 1.6%, P = 0.244) or finding of an elevated hsTnT levels (41.8% vs. 31.4, P value 0.063) between the two influenza types. Moreover, similar to a previous study [17] both myocarditis and pericarditis were rare complications of influenza and were not significantly different between the two types of influenza. In addition, these complications remained similar between the two groups in individual years between 2016–2019. These finding suggest that both influenza strains A and B are equally associated with cardiac complications.
Pneumonia is a major complication of influenza that may be associated with mortality, other common complications arise due to exacerbation of chronic medical issues, while cardiac and neurological complications e.g. encephalitis are rare [23, 24]. Known risk factors for complications of influenza include: older age, preexisting cardiopulmonary disease, immunosuppression, obesity, neurological and other common medical conditions [25, 26]. In our study, complications were common and pneumonia developed in 7.2% of influenza patients, of whom, 18.9% developed respiratory failure, however, we could not find any significant difference in clinical outcomes among patients who developed complications between the two influenza types. Cohen et al [17] in their study in hospitalised influenza patients, found that 19% of influenza patients developed pneumonia but there were no differences in outcomes between influenza A and B. The higher rate of pneumonia in their study was likely related to the higher prevalence of multi-morbidity in their patients as reflected by the higher mean CCI (4.3 vs. 1.3) compared to our population.
In our study, a significantly higher proportion of patients who had influenza B developed septic shock as compared to those who had influenza A (3.8% vs. 0.5%, P < 0.001). Patients with influenza B, who developed septic shock were more likely to be younger than 60 years and had a diagnosis of pneumonia and a lower CCI than influenza A. Moreover, there were no significant differences with respect to receiving Oseltamivir or antibiotics between the two groups (P > 0.05). This indicates that influenza B in some cases may cause a severe illness in previously well individuals. Previous literature has not looked into this clinical outcome, however, case reports [26, 27] suggest that influenza B can pose a risk of severe secondary infection in previously healthy individuals.
We found no significant differences in clinical outcomes such as LOS, inpatient mortality and mortality and readmissions within 30 days following hospital discharge among patients with influenza A and B. In addition, the annual rates of these outcomes over the four influenza seasons, between 2016–2020, were similar between influenza A and B (P > 0.05), indicating similar virulence pattern of the two influenza types during this period. These results are similar to previous studies [17, 28] who also found no difference in LOS and in hospital mortality between influenza A and B viral infections, however, data on long term clinical outcomes after hospitalisation for influenza are scarce. These results indicate that contrary to some of the previous studies [28, 29] influenza B cannot be regarded as a milder infection as compared to influenza A especially among hospitalised patients.
In terms of clinical outcomes such as LOS and mortality, our results are similar to previous studies conducted even in hospitalised paediatric populations which also showed no significant differences in these outcomes between influenza A and B patients [30, 31] Some studies suggest that outpatients with influenza A (H3N2) sought care earlier than influenza B and influenza related mortality was highest during influenza A (H3N2) predominant seasons [6, 32]. Our study has limitations as we did not have information about influenza A subtypes thus stratification of analysis according to influenza A subtypes could not be performed.
The use of anti-viral treatment in our study was only 24.5% and significantly more patients who had influenza A received antivirals than influenza B. These results are significantly lower than that reported by a U.S. study [33], who found that 80% hospitalised adult influenza patients had received anti-viral treatment. These differences could be related to the lack of diagnostic confirmation of influenza during the recommended period for anti-viral treatment recommendation (i.e. within 48 hours of onset of symptoms) [34]. However, similar to other studies [35, 36] we also found that hospitalised influenza patients, who received antiviral treatment were more likely to have a less severe illness as reflected by fewer ICU admissions (19.8% vs. 24.9%) and significantly lower in hospital mortality (1.1% vs. 2.5%, P < 0.05) than those who did not receive anti-viral therapy.
This study has some limitations. Information about vaccination status of the participants was unavailable. Evidence [37], suggests that influenza vaccination reduces cardiovascular events and mortality and it is possible that vaccination may have impacted mortality in this study as annual influenza vaccination coverage in adults in Australia is 54% [38].