Respiratory Syncytial Virus in Adult Patients at a Tertiary Care Hospital in Germany: Clinical Features and Molecular Epidemiology of the Fusion Protein in the Severe Respiratory Season of 2022/2023

Abstract

Following an interseasonal rise in mainly pediatric respiratory syncytial virus (RSV) cases in Germany in 2021, an exceptionally high number of adult cases was observed in the subsequent respiratory season of 2022/2023. The aim of this study was to compare the clinical presentation of RSV infections in the pre- and post-SARS-CoV-2 pandemic periods. Additionally, the local epidemiology of the RSV fusion protein was analyzed at a molecular genetic and amino acid level. RSV detections in adults peaked in calendar week 1 of 2023, 8 weeks earlier than the earliest peak observed in the three pre-pandemic seasons. Although the median age of the adult patients was not different (66.5 vs. 65 years), subtle differences between both periods regarding comorbidities and the clinical presentation of RSV cases were noted. High rates of comorbidities prevailed; however, significantly lower numbers of patients with a history of lung transplantation (p = 0.009), chronic kidney disease (p = 0.013), and immunosuppression (p = 0.038) were observed in the 2022/2023 season. In contrast, significantly more lower respiratory tract infections (p < 0.001), in particular in the form of pneumonia (p = 0.015) and exacerbations of obstructive lung diseases (p = 0.008), were detected. An ICU admission was noted for 23.7% of all patients throughout the study period. Sequence analysis of the fusion protein gene revealed a close phylogenetic relatedness, regardless of the season of origin. However, especially for RSV-B, an accumulation of amino acid point substitutions was noted, including in antigenic site Ø. The SARS-CoV-2 pandemic had a tremendous impact on the seasonality of RSV, and the introduction of new vaccination and immunization strategies against RSV warrants further epidemiologic studies of this important pathogen.

Keywords: RSV; fusion protein; molecular epidemiology; respiratory infections; respiratory viruses.

Figure 1

Monthly distribution of total number of samples tested and new RSV cases (n = 343) stratified by RSV-A and -B. Note the two different y-axes: the left y-axis refers to the bar charts and shows the absolute number of detected RSV cases while the right y-axis refers to the absolute number of samples tested, as represented by the line graph. The x-axis is labeled according to the definition that was used to define the start and end of a respiratory season.

Figure 2

Monthly distribution of RSV cases (n = 343), positivity rates of the RSV assay, and mean air temperature during the study period. Note the two different y-axes: the left y-axis refers to the absolute numbers of detected new RSV cases (light gray bars) while the right y-axis refers to the mean temperature of the respective month [°C] (dark gray line) and the positivity rates for adult patients [%] (black dashed line). The x-axis is labeled according to the definition that was used to define the start and end of a respiratory season.

Figure 3

Relative distribution of RSV cases (n = 343) stratified by age. The lines represent the relative number of cases detected in the age group indicated. The 2017/2018, 2018/2019, and 2019/2020 seasons were designated “pre-pandemic”.

Figure 4

Molecular phylogenetic analysis of the RSV-A F gene by the maximum likelihood method. The evolutionary history was inferred using the maximum likelihood method based on the Tamura–Nei model [39]. The tree with the highest log likelihood (−4744.71) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Joining and BioNJ algorithms to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 75 nucleotide sequences. There were a total of 1725 positions in the final dataset. Evolutionary analyses were conducted in MEGA7 [38]. Only nodes with statistical support > 80% are shown. The following symbols indicate the sequence origin or the season of the indicated strain: dots/squares. Red, RSV-A prototype strain; green: season 2017/2018 isolates; orange, season 2018/2019 isolates; purple, season 2019/2020 isolates; blue, season 2021/2022 isolates; black, season 2022/2023 isolates; squares, fatal cases; black triangle: consensus reference sequences according to Goya et al. [16]. Amino acid changes in sites Ø and II with regard to the GA2.3.5 consensus sequence (red) are given in brackets.

Figure 5

Molecular phylogenetic analysis of the RSV-B F gene by the maximum likelihood method. The evolutionary history was inferred using the maximum likelihood method based on the Tamura–Nei model [39]. The tree with the highest log likelihood (−4220.58) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Joining and BioNJ algorithms to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 105 nucleotide sequences. There were a total of 1725 positions in the final dataset. Evolutionary analyses were conducted in MEGA7 [38]. Only nodes with statistical support > 80% are shown. The following symbols indicate the sequence origin or the season of the indicated strain: dots/squares. Red, RSV-B prototype strain; green: season 2017/2018 isolates; orange, season 2018/2019 isolates; purple, season 2019/2020 isolates; blue, season 2021/2022 isolates; black, season 2022/2023 isolates; squares, fatal cases; black triangle: consensus reference sequences according to Goya et al. [16]. Amino acid changes in sites Ø and II with regard to the GA2.3.5 consensus sequence (red) are given in brackets. Note that for the RSVB/Leipzig/2022/17 strain, no amino acid change was noted at position 209 (wtQ209).