Discussion
Respiratory Syncytial virus is the most common cause of serious respiratory infection in infants. Reinfections occur commonly, including in older adults16. In recent years, the importance and severity of RSV infections in children as well as adults has been demonstrated and appreciated1-7. RSV-associated in-hospital mortality increases exponentially with age, posing a greater risk for older adults, particularly frail and high-risk patients8,9,17,18 .Moreover, RSV infection may result in greater morbidity and mortality among older hospitalized adults than influenza19. RSV can also causes substantial outpatient illness with lower respiratory tract involvement. Belongia et al found the virus in the 11% of patients20. In a previous job in our Hospital this incidences reached 14% when children was principally studied21.
It has been already reported that during the SARS-Cov2 pandemic, mitigation measures were associated with marked reductions in non-COVID-19 respiratory infections9,22. In this study, the overall incidence over 6 seasons was 3.3%, but a large difference was observed before and after the pandemic: in the first three seasons, the incidence reached 7.1% and decreased to 1.8% during the pandemic years
RSV was more common in children (9.1%) than in adults (1.14%), but can be found in any age group. Moreover, if we analyze the first two seasons (before the pandemic), the incidence in those over 70 years of age is similar to that in children aged one to five years. And the incidence is not negligible in the rest of the age groups. As noted above, the measures taken during the pandemic reduced viral transmission, especially in adults, where more pressure and control was exerted. The return to normality, even with the lessons learned, suggests that the incidence of RSV infection is likely to rise again.
RSV may be associated with escalation in respiratory support and an increased level of support in living situation at discharge23. RSV disease burden in adults aged more than 60 years in high-income countries is higher than previously estimated24. RSV hospitalizations were associated with increased attributable short-term and long-term healthcare costs1. Therefore, interventions that could prevent RSV may reduce healthcare burden. Understanding the clinical features and symptomatology of RSV infection can help to address the challenges related to case identification and management and allows for the implementation of appropriate preventive measures. For example, in this study incidence decreased from 5.6% pre-pandemic to 0.6% during SARS-Cov2 pandemic.
Since two types and several genotypes have been described and the behaviour of each may be different, an exact classification is necessary. Types RSV-A and RSV-B are simultaneously present in most outbreaks, but RSV-A is associated with severe disease. In RSV-A dominant years typically started, reached its peak and lasted than in RSV-B dominant years8,25. Several distinct genotypes within these types predominate within a community; the dominant strains shift yearly, perhaps accounting for frequent reinfections25,26. Previous RSV infection does not appear to protect against reinfection27. On the other hand, several substitutions in fusion protein reduce nirvesimab susceptibility28, the new monoclonal antibody approved to immunize against RSV.
In this job, RSV-A and RSV-B were found simultaneously, but with very different incidence. In the first two seasons, RSV-B was predominant, but in 2019 (pre-pandemic SARS-Cov-2) there was a subtype shift and RSV-A was detected in 78% of cases, suggesting greater severity of symptoms. The measures taken in the pandemic significantly reduced respiratory infections, as discussed above9,22 .In the first two years of the pandemic a new subtype shift was observed and again RSV-B became dominant. In the last season (2022-23) epidemiological control measures were again relaxed and both subtypes were observed to circulate in the same proportions.
Next season we will have to watch out whether RSV-A (or certain genotypes of this type) replaces RSV-B, as suggested by other studies29,30, as a worsening of symptoms is to be expected. This is why
sequencing of viral strains is relevant not only for taxonomic purposes, but in order to better understand the epidemiology as well as the development of therapeutic and preventive strategies.
The genotyping analysis of RSV was used to characterize which genotypes circulated in Asturias and to investigate whether phylogenetic clusters occurred in the study period.
RSV genotypes ON1 (type A) and BA9 (type B) became the predominant genotypes worldwide from 2015 and were the only genotypes detected in the period 2021-2022 in Asturias. Variants of these genotypes are constantly generated, so it is necessary to identify them31. Numerous variants of the ON1 genotype have been reported worldwide, with various amino acid substitutions32,33. In a last study in USA in 2023, Goya et al did not find specific changes34.
In Asturias, in the ON1 genotype, the gain of the K205N mutation that was only found in two NCBI strains (ON237320 Argentina 2017 and KX827403 Guatemala 2013) and the Y280H mutation (common in the world and found in Spain) formed a separate sublineage in 26 sequences. This variant was found in 2022 in a similar number of men and women, mostly being under 6 years of age. Besides, the gain of the S299I mutation in 8 sequences found in strains without duplication of ON1 (KT765684-KT 765686, OK458608-OK458615 Kenia 2006-2010) generated another new sublineage. This variant was found in 2022 mostly in men, also mostly in children less than 6 years of age, but not exclusively.
From VRS-B, in Europe the BA9 genotype is always the predominant, as was also reported in Catalonia ( Spain)32,35. In Asturias, in 12 sequences the BA9 genotype, the gain of the mutation S263G, that was only found in two NCBI strains (OK078747 Pakistan 2010 and MH606068 Croatia 2017), formed a separate sublineage. This variant was found in 2021 in women under 6 years of age; it continued to be disseminated in 2022 in people over 65 years of age mainly in men.
Therefore these new sublinages can be found in any group of individuals. On the other hand, variants without these mutations were previously detected in Asturias, supporting the idea that they were locally generated, in contrast to the finding of Goya et al34.
When the GenBank sequences were examined, no new mutations were observed, but rare mutations appeared in new lineages, which could be limited to local transmission. New substitutions may contribute to antigenic escape, promote transmissibility, or be the result of the founder effect in a vulnerable population. Therefore, performing genotypic characterisation studies locally and sharing them with the rest of the scientific community should be a practice to be implemented in the control of this type of infections.
Limitations of the study are that few clinical data were available, that the number of patients sequenced is limited, that changes in the frequency of circulation of RSV genotypes in previous seasons cannot be addressed and that the analysis was based only on a fragment of the G gene.