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.