Discussion
In this comprehensive cohort review, we have described the epidemiology, resource utilization, and outcomes of ALRI caused by one viral pathogen versus multiple viral pathogens in children requiring hospitalization. In our study, the overall mortality in children suffering from ALRI was low and showed no significant difference in the two groups, even with the inclusion of patients with comorbidities. However, patients with viral co-infections had a longer hospital stay, more utilization of high flow nasal cannula, higher possibility for escalated care and intubation, and increased cost of care.
Interestingly, rhino/enterovirus had the highest detection rate among children admitted with ALRI, accounting for 50% of all cases. This result differs from previous viral epidemiology
studies 3, potentially because we only included patients that tested positive using respiratory pathogen array while patients tested with RSV antigen and rapid flu tests were excluded. RSV was the second most common isolated virus found in 16% of our population. Viral co-infections were reported in 16.2% of all cases admitted to our hospital with ALRI, which is relatively lower than the prevalence rates reported in previous studies6,11,13,14. These differences in viral co‐detection rates might reflect variations in case selection and possible technical limitations. Even though COVID-19 was not isolated in our population and is known to vary genetically from the coronavirus identified in this study, it was reported that COVID-19 had the same pattern of co-infection with other respiratory viruses in the recent pandemic15,16. Data regarding COVID-19 is still evolving, but our results from this study might help in comparing outcomes of COVID-19 co-infection versus other viral co-infections in children. The higher proportion of infants among patients who had viral co-infections might be explained by the susceptibility of this age group to recurrent viral infections, immature immune response, higher rates of asymptomatic nasopharyngeal colonization, and prolonged shedding of rhino/enterovirus and RSV 17, 18, 19, 20, 21, 22, 23.
Patients with cancer were more likely to have one virus isolated rather than a combination of two or more viruses in our cases, which contrasts with prior studies that have shown a higher percentage of viral co-infections in pediatric patients with cancer and neutropenia24, 25.
Clinical course of patients with viral coinfection in our study was more severe, as depicted by the aforementioned variances (length of stay, high flow nasal cannula, intubation). Our contemporary data is similar to what has been reported in the literature 8-10.
A higher rate of patients with viral co-infection had a positive respiratory culture within 24 hours of hospital admission in comparison to patients with a single viral infection, which might be explained by the higher proportion of intubation in patients with viral co-infection, even though the difference was statistically not significant. Patients admitted with viral co-infections were more likely to get chest x-rays. This might be attributed to the lower age group that was infected with multiple viruses and their relative severe clinical presentation.
Our study is the first to report the hospital cost of care for children with respiratory viral illnesses. Cost of care was high in patients with coinfections, even though the difference did not reach statistical significance. The overall cost of care to manage viral infection related admissions in children was low compared to other expenses in the healthcare industry.
Our study has several limitations. First, it was conducted retrospectively and from automated data extraction only which carries the possibility of incorrect charting. Also, identification of comorbidities was based on ICD codes entered by providers on admission. Second, the duration of viral shedding, as detected by RPA-PCR, is significantly longer than the culture of the same virus and could even reflect virus left over from a previous infection rather than a true active infection. Third, the significance of multiple viral detection remains poorly understood, given that PCR can sometimes detect a viral respiratory shedding in asymptomatic children 14,19. Previous literature reported that hCoV and hBoV PCR were frequently detected in healthy controls, suggesting that caution is needed when inferring a causal relationship between viral detection and respiratory diseases in symptomatic and asymptomatic patients 26.
In conclusion, we have described the epidemiology of single respiratory viral illnesses versus multiple viral co-infections in children, including their comparative resource utilization and outcome. Appropriate identification of respiratory viruses can help us in isolating patients appropriately, as well as recognizing patients that might need escalated respiratory care, especially those with viral co-infections. Our study ended before the emerging COVID-19 was reported in the United States. However, the data can help us understand the disease course of COVID-19 and the role of viral co-infections in altering the inflammatory response in the pediatric population.