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.