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.