The study analyzed clinical and direct medical cost data of 130,084 patients hospitalized with a primary ICD-10-coded diagnosis for RSV lower respiratory tract disease during the years 2010–2019 in Germany. The large majority were children < 4 years old, previously healthy and with low rates of severe complications and intensive care treatment. Children who were 5–17 years old were few, had higher proportions of risk factors/underlying chronic conditions and more often required intensive care.

Adults and seniors accounted only for 1% and 4%, respectively, of the total number of RSV-coded hospitalizations in the 10-year period, but had higher proportions of risk factors/underlying chronic conditions, complications, intensive care treatment, ECMO treatment, and in-hospital fatalities when compared to children. In fact, in-hospital fatality rate steadily increased with patient age, with 76% of all 599 reported fatalities observed in seniors. During study years 2017–2019 there was a sudden increase in the number of adults and seniors with an RSV-coded hospitalization. Consequently we also observed a sudden increase in the number of fatal cases during this time period (data not shown). Previous studies had already shown that acute RSV LRTI in adults with significant underlying chronic conditions can lead to severe, often life-threatening, complications [22, 23]. Especially adults with comorbidities, such as chronic respiratory disease, cardiovascular disease, and compromised immune systems, have an increased susceptibility to severe RSV disease that requires hospitalizations [24,25,26,27]. A systemic literature review by Savic et al. [28] found the in-hospital fatality rate of RSV patients ≥ 60 years old in high-income countries to be 7.1%, which is similar to the presented in-hospital fatality rate of 8.0% in seniors > 59 years old in Germany.

An interesting observation on clinical treatment was that 30.5% of children with RSV-coded hospitalization were isolated as a prophylactic measure, in contrast to higher proportions in adults and seniors. We suspect that the isolated adults and seniors with RSV-coded hospitalizations often represented high-risk patients.

The overall number of adult and senior RSV-coded hospitalizations or RSV-associated pneumonia was low compared to patients with influenza-coded hospitalizations or influenza-associated pneumonia, which accounted for hospitalizations of 34,829 adult and 73,286 senior patients during the same 10-year observation period in Germany, including 6,885 and 24,235 patients with influenza-associated pneumonia [17].

In all study years, the hospitalization incidence based on RSV-coding was considerably higher among children (in 2019, 123.5 times higher than adults and 10.1 times higher than seniors). While hospitalization incidences were below 0.2/100,000 in adults and below 1.0/100,000 in seniors from 2010 to 2015, a conspicuous increase was observed from 2016 to 2017 (2.5-fold in adults, 5.1-fold in seniors) and a further increase from 2018 to 2019 (2.1-fold in adults, 2.4-fold in seniors). This increase was not observed in the children population. Hence, it may be more likely attributed to an increasing awareness of RSV as a possible cause of severe disease among adults and seniors and, consequently, an increasing use of virological testing rather than to a change in virus characteristics. Rapid molecular testing for RSV seems to contribute to better patient outcomes in older adults; however, it is not widely implemented in healthcare settings [29]. Seniors are known to be inconsistently tested for RSV in hospitals, meaning the knowledge on the impact of the true effects of the disease is incomplete [29]. Adults commonly have low viral titers and an overall shorter duration of viral shedding compared to children, which may limit RSV detection and diagnosis [30]. Since our study specifically focuses on patients with an ICD-10-coded RSV primary diagnosis usually based on laboratory confirmation, the difficulty associated with testing adults can definitely impact the number of adults and seniors included in our analysis.

The hospitalization incidence may also be affected by our case definition, selecting the well-defined group of patients with an RSV code as primary diagnosis. Hence, in addition to this main analysis group (‘Validated’ cases), we additionally performed an analysis on two further patient groups with broader inclusion criteria: (i) a group that included RSV infections as primary diagnosis plus RSV infections listed as any secondary diagnosis as long as the primary diagnosis was a “J” ICD-10-GM code indicating a disease of the respiratory system (‘Searched’ cases), and (ii) a group that included all patients that had either a primary or a secondary diagnosis of RSV (‘Reported’ cases). The results of these additional analysis revealed that there was little difference in the age distribution among the three analysis groups (Supplementary Table S5). The overall number of patients included was similar among the Validated, Searched, and Reported groups (130,084 vs. 138,264 vs. 149,368), and the distributions of selected risk factors/underlying chronic conditions, complications, and treatments were also similar. Children were still the large majority in all analysis groups. It is important to note, however, that the ‘Reported’ group had a higher proportion of adults and seniors—almost double compared to the ‘Validated’ group. This is most likely the case because ‘Reported’ cases included approximately 19,000 patients with RSV as a secondary diagnosis and a constantly higher rate for patients with selected risk factors/underlying chronic conditions compared to the ‘Validated’ group. This also translates to the overall in-hospital fatality rate, essentially doubling in the Reported group, with the majority of fatalities again in the senior age group.

The cost analysis quantifies the direct healthcare costs of RSV-confirmed hospitalizations in Germany from January 2010 to December 2019. In the 10 years included in the study, 130,084 hospitalized patients with an ICD-10-coded primary RSV infection (J12.1/J20.5/J21.0 primary diagnosis) amounted an estimated 482,237,871€ in just direct costs. The highest mean per patient costs were reported from 2017 to 2019. However, the higher costs do not reflect higher costs due to a more serious course of disease or due to a higher number of elderly patients with RSV during these years.

In a similar study conducted by our research group looking at the per-patient cost of influenza-coded hospitalizations in Germany, the mean cost for all influenza patients over the same 10-year span was 3521€, which is lower (by 186€) to that of RSV-related hospitalizations in our study [17]. The median per-patient cost for influenza-coded hospitalizations is almost half of that of RSV-coded hospitalizations (1805€ vs. 3550€), which may be due to the fact that the ICD-10-GM codes for influenza available as primary codes are not restricted only to patients with LRTI but may also cover less severe manifestations of the disease.

In the present study, adults and seniors had the highest per-patient costs. In fact, the mean (± SD) per-patient cost for all patients hospitalized due to an RSV infection peaks among seniors 60–69 years old: 8630€ (± 18,737€) (Supplementary Table S3). Other studies on RSV burden have concluded that driving factors of increased costs are older age and the presence of risk factors/underlying chronic conditions [31]. Similarly, in our previous influenza study, patients 60–69 years old also reported the highest per-patient cost.

Our analysis also shows that children 10–17 (who are usually not considered when discussing RSV) had higher per-patient costs than the other children age groups, probably due to their higher rate of risk factors/underlying chronic conditions for a severe course of disease. Children 15–17 years old had a median per-patient cost of 3977€ while children < 1 year old reported a median per-patient cost which is actually lower than the overall median per-patient cost of 3550€. Mean costs per-patient followed a similar trend. In fact, the median and the mean costs of children 10–14 and 15–17 years old were more similar to that of adults 18–59 and > 59 years old than that of younger children.

When comparing the difference in cost between the risk factors/underlying chronic conditions of patients hospitalized due to an RSV infection, it is obvious that all selected risk factors/underlying chronic conditions in our study increased the total cost for each patient. Adults and seniors had the highest rates of immune disorders as well as the highest rates of sepsis, ARDS, intensive care, and ECMO treatment, all factors with high impact on costs. However, the risk factor/underlying chronic condition that had the greatest x-fold change between those affected and those unaffected was found in children, namely prematurity-related disorders (2.68-fold increase). This emphasizes the fact that premature infants are particularly vulnerable to RSV infections and require more costly care.

There are some relevant limitations to the interpretation of our study results. RSV diagnostic testing is not routinely performed in adult and senior patients upon presenting at the hospital with respiratory symptoms, most likely due to the lack of specific antiviral therapy [29]. In addition, since DeStatis only reports costs reimbursed by the German sickness fund, out-of-pocket payments are not calculated in the costs reported by our analysis. Our study has particularly great external validity since the entire German population is included, but there is low internal validity due to potential coding issues,—especially since all hospitals in Germany are included [17]. ICD-10-GM codes chosen (J12.1, J20.5, and J21.0) were specific for patients who had either tested positive for RSV or were classified as RSV patients due to the epidemiological situation and had received a primary diagnosis of an RSV infection. However, this method does not capture hospitalized patients who might have had an RSV infection but were not tested or RSV disease was not suspected from the epidemiological situation. If solely the primary diagnosis is used to identify patients with RSV-coded hospitalization (Validated’ cases), the true number may be underestimated, as shown previously on the burden of influenza-associated hospitalizations [17, 32]. In contrast, including all patients with any primary or secondary diagnoses of RSV (‘Reported’ cases) are likely to overestimate the true hospitalization incidence, as this group may include patients with an RSV-unrelated primary diagnosis and ‘incidental’ RSV infection. Therefore, it is evident that our main analysis represents only a minimum estimate of the true burden of disease of RSV hospitalizations.