Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults

Abstract

Influenza-like illness (ILI) can be caused by a range of respiratory viruses. The present study investigates the contribution of influenza and other respiratory viruses, the occurrence of viral co-infections, and the persistence of the viruses after ILI onset in older adults. During the influenza season 2014-2015, 2366 generally healthy community-dwelling older adults (≥60 years) were enrolled in the study. Viruses were identified by multiplex ligation-dependent probe-amplification assay in naso- and oropharyngeal swabs taken during acute ILI phase, and 2 and 8 weeks later. The ILI incidence was 10.7%, which did not differ between vaccinated and unvaccinated older adults; influenza virus was the most frequently detected virus (39.4%). Other viruses with significant contribution were: rhinovirus (17.3%), seasonal coronavirus (9.8%), respiratory syncytial virus (6.7%), and human metapneumovirus (6.3%). Co-infections of influenza virus with other viruses were rare. The frequency of ILI cases in older adults in this 2014-2015 season with low vaccine effectiveness was comparable to that of the 2012-2013 season with moderate vaccine efficacy. The low rate of viral co-infections observed, especially for influenza virus, suggests that influenza virus infection reduces the risk of simultaneous infection with other viruses. Viral persistence or viral co-infections did not affect the clinical outcome of ILI.

Keywords: influenza virus infection; influenza-like illness; older adults; respiratory viruses; viral co-infections; viral interference.

Figure 1

Flow diagram of enrollments. Influenza-like illness (ILI) cases (2014–2015) (A) and the subgroup of asymptomatic controls (B). A subject could have multiple ILI episodes per season. Per protocol was defined when the sample was taken <72 h after start of fever. For the recovery visit, the window was 7–9 weeks after ILI onset. Subjects were considered lost to follow-up if they did not respond to the end of study mailing and had no ILI visit. Every month of the study period a fixed number of asymptomatic participants, equally distributed over the different age groups, were invited for swab sampling.

Figure 2

Incidence per virus that were detected in naso- and oropharyngeal swabs of influenza-like illness (ILI) cases in the acute phase (left panel) and at recovery (i.e., 8 weeks later) (right panel) (A) and of first samples of asymptomatic controls, i.e., participants aged ≥60 years, and without ILI symptoms (B) in influenza season 2014–2015. The percentages were calculated per ILI event. Multiple pathogens could be detected in a single event and therefore contribute to the incidence for multiple pathogens. Abbreviations: hMPV, human metapneumovirus; ILI, influenza-like illness; RSV, respiratory syncytial virus.

Figure 3

A calculation was made whether a specific virus co-infection appeared to occur less often than expected based on the frequency of the detected single pathogens in season 2014–2015 (squares). For comparison, the occurrence of viral co-infections in 2012–2013 was studied as well (circles). Results of these analyses are presented as the OR of the odds of being infected with pathogen A when already infected with pathogen B compared to the odds of being infected with a singular pathogen A. The 95% CI, presented as bars, was used to estimate the precision of the OR. Adjusted p-values (p_adj) were calculated, and p_adj < 0.10 was considered as significantly different (indicated with black lines), p_adj > 0.10 was considered as not significantly different (indicated with grey lines).