DISCUSSION
This study provides further insights for the population-based incidence
of laboratory-confirmed respiratory viruses associated with
hospitalization in adults. Our findings may provide more precise
estimates of the incidence of non-influenza respiratory viruses than
previous studies which have often relied on diagnostic codes or
syndromic surveillance, rather than systematic laboratory testing with a
multiplex-PCR assay, and thus, may have underestimated the case burden
[11]. We also evaluated the incidence of respiratory viruses in the
subset of patients > 80 years of age and found that
the incidence in this oldest age strata was consistently more than
double that of patients 65-79 years of age. These findings suggest that
the impact of non-influenza respiratory viruses is likely
underappreciated in the absence of systematic testing of older adults
hospitalized with acute respiratory signs and symptoms. Furthermore,
lack of diagnostic testing could lead to lack of appropriate infection
prevention and control and potential nosocomial transmission.
We found that influenza viruses predictably exhibited a high seasonal
incidence with different types each year. The burden of non-influenza
respiratory viruses was potentially higher than that of influenza
viruses. Non-influenza respiratory viruses collectively had a higher
incidence than that of influenza viruses collectively, although it is
likely that the influenza vaccine reduced hospitalizations and
mortality, particularly when there was a good match between the vaccine
and circulating influenza strains [12]. We found that 2.8 times more
patients were hospitalized with non-influenza viruses (excluding RV/EV)
than with influenza viruses. Overall, the proportion of patients
admitted to an ICU was significantly higher for non-influenza than for
influenza viruses. Mortality was also significantly higher for
non-influenza respiratory viruses. Notably, our analysis of the
collective burden non-influenza viruses could be perceived as an
underestimate as we excluded RV/EV, which was the most commonly detected
virus, as similarly described by others [13]. We chose to exclude
RV/EV from the analysis of the collective burden because RV/EV were the
most commonly co-detected viruses and the mPCR assay used cannot
distinguish rhinovirus from enterovirus nor unique subtypes.
Furthermore, while RV/EV are associated with hospitalizations for ARIs
[14] and exacerbations of underlying cardiac and pulmonary
comorbidities [13-15], prolonged viral shedding is also well
described [16] which could decrease the causal relationship of
detecting these viruses with burden.
Comparison of our findings with other reports is challenging due to
different methodologies including case finding and study population. For
example, past studies exclusively examined older adults> 65 years old and high-risk adults with congestive
heart failure and chronic obstructive pulmonary disorder [6].
Furthermore, much of the morbidity and mortality associated with
non-influenza respiratory viruses has been described in adult long-term
care facilities experiencing outbreaks associated with high attack rates
and high death rates [17, 18]. Nonetheless, our incidence estimates
of influenza hospitalizations were comparable to the Centers for Disease
Control and Prevention (CDC) national estimates for both years [19,
20]. The current study’s rate of ICU admissions from RSV (16.1%) was
similar to that described in previous prospective studies of RSV by
Widmer and colleagues (10%) [3] and Falsey and colleagues (15%)
[6]. The current study’s ICU admission rate of 11.5% associated
with influenza was also similar to that previously described (6%
[3], 12% [6]) as was the 16.5% rate associated with HMPV (13%
[3]).
Some of our observations for the human coronaviruses merit further study
as, to our knowledge, these findings have not been previously reported.
We found a high burden associated with CoV 229E and CoV HKU1 as these
(in addition to AV) had the highest rates of ICU admission and highest
mortality rate. Among all the viruses studied, the combined CoV types
had the highest incidence estimates for patients 18-49 and 50-64 years
of age for both years. We found similar seasonality among the human
coronavirus types as has been reported by the Centers for Disease
Control and Prevention (CDC) and National Respiratory and Enteric Virus
Surveillance System NREVSS [19-21]. However, the most common CoV
type found by laboratories participating in NREVSS in 2018-2019 was
CoVOC43, while we found CoV229E and CoVOC43 to be the most common types
that season. While surveillance reports from the NREVSS provide trends
for and seasonality of respiratory viruses, these reports lack
patient-level characteristics to inform age-related trends or patient
outcomes. It remains to be seen if seasonal variations in the human
coronavirus will impact the epidemiology of the COVID-19 pandemic or be
a source of false positive serologic results for SARS-CoV-2 or even if
SARS-CoV-2 could eventually become a seasonal virus.
This study has limitations. It was performed at a university affiliated
tertiary care referral center in New York City which limits
generalizability. We did not consider the impact of influenza
vaccinations on hospitalization rate. Viral detections may not have
represented acute infection as mPCR does not distinguish between viable
and non-viable virus. Case detection may have been decreased if not all
patients were tested for respiratory viruses, particularly outside
influenza season. However, the study period aligns with a prospective
surveillance study of RSV in hospitalized adults conducted in the same
facilities in which we found that nearly all hospitalized patients
meeting ARI criteria during the respiratory viral season, October to
April, were tested by treating clinicians [22]. Finally, while the
case definition required viral detection within three days of admission,
we did not measure the burden of illness in cases that were acquired
during hospitalization or in patients transferred to our hospital who
had been tested at outside facilities.
In conclusion, the burden of non-influenza respiratory viruses is
substantial, particularly for older adults who lack durable immunity for
respiratory viruses and frequently have comorbid conditions that
increase their risk of severe disease. Thus, prevention and treatment
strategies for non-influenza respiratory viruses, including effective
vaccines, are needed. Future research should further assess the clinical
impact of specific human coronaviruses and the potential impact of
specific coronavirus types on the epidemiology and impact of SARS-CoV-2.