BREAKING! Scientists Discover New Circulating RSV Virus Variants That Is Causing Prolong Infection Especially Among Infants And Young Children!

In early November, Thailand Medical News had called for various international research teams to look into the possibility of new respiratory syncytial virus or RSV variants emerging that could be causing anomalous manifestations in the current RSV surge that is affecting many countries globally especially the United States as there has not been any studies done in the last two years since the emergence of the COVID-19 pandemic, to monitor the evolution of the RSV virus especially considering the fact that the SARS-CoV-2 virus has changed the human immune landscape tremendously and this could be a contributing factor to the evolution of other pathogens.
https://www.thailandmedical.news/news/warning-adults-can-also-contract-rsv-infections-and-its-usually-severe-in-the-aged-is-the-current-rvs-wave-due-to-newly-emerged-strains
 



An international team of researchers involving scientists from the Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne-Switzerland, the University of Pittsburgh -USA,Vanderbilt University Medical Center-USA, the Swiss Institute of Bioinformatics - Switzerland and Emory University School of Medicine and Children’s Hopsitla-USA took to the task and discovered shockingly that indeed new RSV variants or strains have evolved and was causing prolong infection that was being commonly seen in infants and young children in the current surges although respiratory syncytial virus (RSV) are typically only involved in short acute respiratory infection.
 
The study team first identified those with prolonged RSV infection among healthy term infants and conducted 1) a human GWAS to test the dependence of infection risk on host genotype, 2) a viral GWAS for association with prolonged RSV infection using RSV whole-genome sequencing, 3) an analysis of all viral public sequences, 4) an assessment of immunological responses, and 5) a summary of all major functional data. Analyses were adjusted for viral/human population structure and host factors associated with infection risk.
 
The study team identified two new variants ie. p.E123K/D and p.P218T/S/L in G protein that were associated with prolonged infection (Padj = 0.01).
 
They found no evidence of host genetic risk for infection. The RSV variant positions approximate sequences that could bind a putative viral receptor, heparan sulfate.
 
The study findings utilizing analysis of both viral and host genetics clearly showed novel RSV variants that were associated with prolonged infection in healthy infants and no evidence supporting host genetic susceptibility to infection. As the capacity of RSV for chronicity and its viral reservoir are not defined, these findings are important for understanding the impact of RSV on chronic disease and endemicity.
 
The study findings were published in the peer reviewed publication: The Journal of Infectious Diseases.
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac442/6827492?login=false
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The human orthopneumovirus, more commonly known as the respiratory syncytial virus (RSV), can lead to significant mortality and morbidity worldwide though many assume that it is merely a mild infectious respiratory disease.
 
Typically, most children between the age of two to three years are infected by RSV at least once. RSV mainly infects the lower and upper respiratory tract epithelium; however, it has also been found in non-airway sources. Although RSV typically causes acute respiratory infection, it can also lead to persistent or prolonged illness in some individuals.
 
Interestingly, the prolonged shedding of RSV in infants after the first infection has been observed to increase the average duration of viral shedding. However, whether specific viral factors result in prolonged infection in infants is not known.
 
Fully comprehending the characteristics of prolonged infection is essential, as it can increase transmission rates and cause developmental changes to the airway epithelium of young patients.
 
Furthermore, the reservoir for RSV is also not understood, with some strains of RSV believed to remain in circulation at low levels in the community, whereas others may remain seasonal.

The study involved healthy-term infants who suffered from prolonged RSV infection in the current surge.
 
A detailed viral genome-wide association study (GWAS) was performed using RSV whole-genome sequencing to understand the relationship between prolonged RSV infection in infants and viral genotypes.
 
Comprehensive human GWAS was performed to analyze the impact of first-year RSV infection risk on the genotype. In addition, the local immunological response to RSV was assessed, along with an analysis of all viral sequence data. A summary comprising all functional data of the identified variant was provided.
 
In the study, a total of 19 infants met the prolonged infection criteria, defined as acute respiratory infection with two or more RSV polymerase chain reaction (PCR)-positive nasal samples with more than 15 days between the two test dates.
The mean RSV Ct value of the first infection was 25.9, while the second was 31.6. The mean number of days between the two infections was 29 days.
 
The study findings showed that RSV infection had little to no impact on the genotypes of the infants.
 
It was however found that prolonged infection was caused by viruses from different phylogenetic clades compared to a single specific clade. Similar RSV sequences were observed for initial and subsequent viral detection, thus suggesting that these were prolonged infections.
 
A thorough genetic association between prolonged infection and the lead variant was observed, with no other variants found to correlate with the lead variant.
 
The novel p.E123K/D and p.P218T/S/L variant genotypes were primarily associated with prolonged infection; however, information on the effects of the two variants on regional or local RSV G protein structure was insufficient. Additionally, the impact on glycosylation was indeterminate.
 
These newly identified RSV variants that led to prolonged infection in otherwise healthy infants was found to to have no association with host genetic susceptibility.

Importantly, understanding viral and host mechanisms resulting in prolonged infection can be useful in determining strategies that can control both the short- and long-term impacts of RSV infection. In addition, identifying RSV variants causing prolonged infection can also help improve vaccine design.
 
The study team stressed that further research is needed to determine the reservoir for RSV, as well as its capacity for prolonged infection in immunocompetent hosts.
 
It should be note that the current study was not designed to examine the duration of infection and required additional sampling. In addition to a small cohort size, the study team were only able to analyze the host genetic risk for infection rather than prolonged infection. Finally, the modulatory effects of maternal antibody levels on the infants were not measured.
 
For the latest on the current RSV Surges, keep on logging to Thailand Medical News.