Conclusions
The recent emergence of SARS-CoV-2 (COVID-19) has demonstrated the important of surveillance for non-influenza respiratory viruses. Here we present descriptive findings from non-influenza surveillance and how it can provide meaningful information regarding their composition and prevalence. Our goal was to add to the knowledge generated by other studies7, 10-23 regarding viral etiologies associated with URIs aside from influenza viruses in a population of adults characterized as high-risk for influenza complications.
A few studies focusing on high-risk populations have employed multiplex molecular methods. For example, one study illustrated that there was a high incidence of complications related to non-influenza respiratory viruses, and that disease severity was similar to influenza, indicating that surveillance of these viruses is important.10 A large longitudinal retrospective study highlighted that picornaviruses, specifically RhV/EV, are potentially neglected as a significant contributor to the development of disease severity and can lead to lower respiratory infections.14 Lastly, other studies utilizing multiplex molecular methods have highlighted the importance of coinfections15 and diversity of non-influenza respiratory viruses.17
In this population of adults at high-risk for influenza complications, we identified a viral or bacterial respiratory pathogen etiology in 30.1% (241/799) of the total specimens with a co-infection detection rate of 6.6% (16/241). Overall, the pathogens identified, AdV, CoV, hMPV, IV, PIV, RhV/EV, RSV and M. pneumo, are consistent with known causes of URIs, regardless of the specific population.26 We found that RhV/EV was the most common single pathogen detected in high-risk adult ED patients, and other studies have presented similar findings, albeit in military personnel.16, 17
We found that AdV was more commonly associated with coinfections and this finding is supported by previous studies in military recruits15 and a study in hospitalized children that suggested that AdV may play a larger role than previously thought in the development of more severe disease, such as bronchitis and pneumonia.22 The pathogen detection rate and time of year for varied across the sites. The lowest detection rate was observed at JHH, while the highest detection (both mono- and co-infections) observed at MMC. MMC also had the greatest pathogen diversity and was the only site where atypical bacteria were found. While the RhV/EV proportion of pathogens was fairly consistent across the sites, the peak detections for pathogens varied based on time of year. TMC had an early peak of influenza activity, with shifted peak detections of CoV and hMPV observed as compared to the other three sites. Similar results, in terms of temporal variation have been observed in other studies and each of these studies15, 20, 22 illustrated the temporal nature of respiratory virus infections. Situational awareness from broad surveillance may impact patient management.
This study had several limitations. First, it was only conducted over a single season and the numbers of positive tests was too low to make major comparisons. Additionally, because the population had many underlying conditions, there were not many differences found in the clinical outcomes and many confounders exist. Larger scale studies would be needed to make major conclusions on the impact of multiplex methods. However, this study does provide a description of the variety of pathogens found in adults at high-risk of influenza infections who report with influenza symptoms to the ED.
The value and meaningfulness of applying multiplex molecular methods for respiratory viruses aside from influenza virus has been under debate.27, 28 For influenza virus, and in some cases RSV, studies utilizing point-of-care (POC) diagnostic tests for these specific organisms have shown value in terms of patient management, patient cohorting and droplet precautions, and appropriate anti-viral therapy.29-31 However, for large, molecular multiplex methods, it is unclear whether or not they should be employed broadly for general surveillance purposes, or restricted to specific populations, i.e., pediatric patients, high risk ED patients, and the immunocompromised.27 Coinfections are more readily detected on molecular panels, however, clinical consequences of coinfections are not totally clear.27 It has been noted that there are various barriers to utilizing these methods for general surveillance and specific diagnosis. These include difference in testing phase requirements,28 cost to the laboratory, the patient and insurer,27 and level of complexity for the multiplex method.27 Strategies have been suggested to mitigate some of these barriers.28 Surveillance of non-influenza viruses in these populations can aid in differentiating the cause of illness, which can be potentially antibiotic sparing.7, 13, 18-20 Newly developed multiplex diagnostic technologies can aid in non-influenza surveillance and expand the etiology of URIs beyond influenza.7, 18-20
Overall, the applicability, clinical value and value to surveillance efforts of employing multiplex molecular methods may be specific to certain populations, such adults at high-risk for influenza complications, or may be of more benefit when applied locally, to identify small outbreaks of specific viruses not routinely surveyed for, in specific location.