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NEW INSIGHTS INTO RSV DISEASE

In developed countries respiratory syncytial virus (RSV) causes busy epidemics during winter seasons but fortunately with very low levels of mortality in children. However, in developing countries the situation is different. In a recent meta-analysis it was estimated that globally RSV causes more than 100 000 deaths in children <5 years of age every year (Shi et al. Lancet 2017) and RSV is considered the second most important pathogen causing mortality in children only after malaria (Lozano et al. 2012 Lancet). This is something that we pediatricians in Finland and other developing countries often forget when we worry about crowded emergency departments, overfilled wards and busy on call shifts every winter during RSV epidemics. (Read more)

Despite decades of research efforts there are no vaccines against or effective antivirals available for RSV. Vaccine development has been challenging after unfortunate clinical trials with inactivated RSV vaccine in 1960s, which not only failed to protect children from RSV but also caused enhanced disease in RSV naïve children with two study participants dying due to severe disease. Furthermore, as natural infection with RSV fails to produce protective immune response leading to re-infections throughout lifetime, inducing protective immunity will be a challenge also for the vaccine development. We still lack complete understanding of the immunological mechanisms contributing to increased disease severity and poor immune responses in children with RSV.

During my post doctoral training I worked in Nationwide Children’s Hospital in Columbus, Ohio in Asuncion Mejias’ and Octavio Ramilo’s group focusing on immunological host responses in children with viral respiratory tract infections. We used systems analysis approach with an aim to combine flow cytometry derived cellular immunophenotype data and transcriptomic data from peripheral white blood cells with detailed clinical and microbiological data.

In Columbus, we used microarray based methods for the transcriptome analyses but in the past few years more powerful methods have been developed. Microarray based methods have been replaced by RNA sequencing (RNAseq) and advances in microfluidics and nanotechnology have enabled transcriptome analyses at single cell level. Earlier we analyzed pooled RNA from large number of cells but these novel methods allow us to simultaneously obtain thousands of single cell transcriptomes from each patient sample.

After returning from Columbus a few years ago, I first wanted to focus on clinical work in order to advance my pediatric residency but I soon found myself planning new research projects. During the past winter season we started enrolling infants with RSV bronchiolitis in our study where we aim to take advantage of novel methods and use single cell RNAseq to gain better understanding of the host immune responses during RSV infection. The study will be conducted in collaboration with Päivi Saavalainen’s group from the University of Helsinki. Now that the RSV epidemic is over for this year, we will continue to enroll healthy controls. What constantly keeps amazing me is the positive attitude of the parents towards our study and research in general. Even if our study has no potential to help their sick child, they are willing to participate in order to help other children in the future. None of the parents we’ve approached so far have declined to participate in our study and we are truly thankful to all participating families.

I feel privileged to be able to continue research activities in parallel with my pediatric residency. For this I’m grateful for the flexibility of my supervisors in the Children’s Hospital and our residency program in the University of Helsinki and for the support from the Pediatric Research Center.