While the rest of the world deliberates about the logistics of introducing maternal immunisation against RSV, or nirsevimab (a long lasting anti-RSV monoclonal antibody)
Galicia in NW Spain has cracked on with giving nirsevimab to all newborns
What is really impressive ... 1/n is their commitment to releasing their data in near real-time. You can read their latest report from two days ago here:
Report_RSV_week47.pdf () 2/n sergas.es

our paper from the @WHO RSV Surveillance Laboratory Group is now out in the @IsirvEpi journal onlinelibrary.wiley.com/doi/full/10.11…
impressive results for the detection and typing of RSV using RT-PCR from 26 National @WHO collaborating centres globally 1/4 whole genome sequences for the strains used in this External Quality Assessment conducted by @UKNEQAS available @GISAID 2/4

huge amount of recent interest in invasive group A streptococcus (iGAS) infection in children
but up until now little patient-level clinical data on this spike in cases
we hope our case series @TheLancetInfDis will help address this knowledge gap thelancet.com/journals/lanin… 1/n back in the autumn a group of us at the Royal Hospital for Children in Glasgow noticed a spike in empyema cases in children

in Nov 23 alone we looked after 9 children with empyema requiring a chest drain, almost as many as we'd expect to see in an entire year at our centre 2/n

Dr. Ravi Balakrishnan @UKHSA @NPEG12 presents data for TB in England

in 2011 England had high TB notification rates (amongst highest in western Europe) but have been falling since

comprehensive report available (much to learn here for other diseases): assets.publishing.service.gov.uk/government/upl…

https://twitter.com/NPEG12/status/1577924452150611973

fortunately very few paediatric TB cases in England in 2020: 146 2/n

but price is going to be key: how much these interventions costs will determine how widely they are used 6/n another important question is whether it is going to be possible to interrupt community transmission for RSV with a vaccine for infants
the PHIRST study was designed to look at this pubmed.ncbi.nlm.nih.gov/34019838/ for influenza, RSV and later on adapted for SARS-CoV-2 7/n

now @rsv2022 Prof. Cheryl Cohen @WitsUniversity talks about key considerations in implementing an RSV vaccine 1/n these are:
-burden of disease
--in relation to other vaccine preventable disease
--age specific burden
--different severity endpoints
--seasonality
-cost of disease
-cost-effectiveness
-risk groups for severe illness
-pathogen factors
-transmission dynamics- indirect effects 2/n

@rsv2022 @JimBoonyaratana highlights high burden of viral respiratory disease in immunocompromised patients, and multiple viruses that affect them 1/n an attractive approach are cross-neutralising antibodies to a number of respiratory viruses 2/n

a whirlwind tour of burden of RSV, and detection methods, from @NATBASH15 @rsv2022
key messages:
-RSV is common
-RSV co-infection is also common (mainly with other viruses, most commonly rhinovirus, consistently across different countries) 1/n

https://twitter.com/rsv2022/status/1576203702850813952

however if you don't look appropriately you won't find: a SARI definition will under-estimate burden of RSV disease - fever and cough aren't always both present 2/n

moving now to the other end of the age spectrum, @mvcbarnes @rsv2022 introduces us to the confusing situation in severe RSV infection in infants- is it driven by an inadequate or an overactive immune response? pubmed.ncbi.nlm.nih.gov/29688024/ 1/n but seems that transcriptomics might shed some light on this complicated topic

great presentation and looking forward to the final results from @mvcbarnes and her labs @p_openshaw @InThwaiteImmune 2/2

moving on from antivirals we're now hearing from @ChrisChiuLab @rsv2022 about the impact of age on response to RSV infection startsat60.com/media/opinion/… 1/n all this builds on seminal observational work almost twenty years from Ann Falsey @UofR exploring the burden of RSV infection in older and vulnerable adults 2/n

a bumper crop of antivirals being presented @rsv2022; next up is EDP-323 from @EnantaPharma , an RSV L-protein inhibitor 1/n EDP-323 seemed effective in-vitro and in-vivo, but serial passage in culture led to the formation of escape mutants, with mutations identified across the L-protein: in the RdRP, capping domain, and connector domain, clustered around the drug binding site 2/n

now @rsv2022 a talk on ziresovir, a small molecule F protein inhibitor, by Jim Wu pubs.acs.org/doi/10.1021/ac… 1/n presentation of results from the AirFlo trial, a phase III trial in children with RSV
the primary endpoint a change in a bronchiolitis signs and symptoms score
the study found a small, but significant, reduction in signs and symptoms in the ziresovir group at 48 hours 2/n

Richard Plemper @GSUIBMS presenting data from their recent @ScienceMagazine paper science.org/doi/10.1126/sc… @rsv2022
4′-Fluorouridine is a potent antiviral that blocks replication of RSV and SARS-CoV-2 1/n and also data on AVG-233 science.org/doi/10.1126/sc… another oral inhibitor 2/n

the most exciting candidate at present for RSV prevention is nirsevimab, a long-acting monoclonal antibody that targets site 0 in the pre-fusion RSV F-protein

this morning Eric Simoes presented pooled data from 2 large studies looking at the efficacy of this antibody 1/n

https://twitter.com/JimBoonyaratana/status/1575833347405791232

the reason to pool the data from two studies was to look specifically at those infants that had received a weight appropriate dose of the antibody 2/n

great talk just now @rsv2022 from Dr. McMorrow @CDCgov on the burden of RSV disease globally

key question raised previously is whether a year and a half without RSV infection lead to a rebound in infections, particularly in those 12-23 months who were immunologically naive 1/2

https://twitter.com/rsv2022/status/1574499617735057410

data shown here from the New Vaccine Surveillance Network does show an small increase from 3.9% to 4.7% in RSV-associated hospitalization rates in those 12-23 months

reassuring data for those concerned there might be rebound infections if all infants receive nirsevimab 2/2

now a primer from @LindsayBbent @RSV2022 on our current molecular understanding of RSV

starting with the function of all the difference proteins, with a focus on F and G and their role in inducing protective immunity and neutralising antibodies 1/2 her key messages:
-this virus is complicated
-our understanding of the genetics and molecular biology of RSV has been key to the development of vaccines and therapeutics 2/n

Ruth Karron @rsv2022 outlines key issues in the field RSV vaccines at the moment:

1. Correlates of protection, including the consideration of sterilizing vs non-sterilising immunity 1/n

path.org/resources/rsv-… 2. Possibility of rebound RSV disease following passive prophylaxis?
-not observed in second year of life in motavizumab trial
BUT
-differences in second year of life could be misinterpreted if pool of susceptibles diminished amongst placebo recipients 2/n

I’m a Junior Doctor … Get Me Out of Here!

A 🧵on why, and how, being a trainee medic lost its fun 1/n I just came off a busy week in the hospital- 5 days of acting up as a consultant, and a weekend on call as a senior registrar
It was difficult, challenging, often emotional, stressful and tiring ... 2/n

our paper is now out @Nature ! nature.com/articles/s4158…

a 🧵on the excitement and value of Basic Science, DNA replication and repair, teamwork and collaboration, and the fundamental incompatibility of LEGO and DUPLO 1/n as a clinician scientist, a common question from those around me, as summarised by my son, is :

"why are you going in to work at the lab when you could be saving lives RIGHT NOW in the hospital?" 2/n

interesting paper (with excellent editorial from Jianzhi Zhang nature.com/articles/d4158…) that proposes an "adaptive mutation bias" reducing mutation rates in functionally constrained regions of the genome

so what would Delbrück and Luria think? genestogenomes.org/luria-delbruck… 1/3

https://twitter.com/Grey_Monroe/status/1481298489191837701

as Jianzhi Zhang points out, there are two logical possibilities here:
1) natural selection might lead to the evolution of machinery that reduces mutations in essential genes/regions, where a mutation is highly likely to be deleterious 2/4

my article on childhood viral respiratory diseases is now out @RoyalSocBio rsb.org.uk/biologist-feat… (delighted to be sandwiched in between a piece on oxylipins and another on latent lepidopterans)🧵 I highlight the increasing burden of childhood viral respiratory disease on hospital services edinburghlive.co.uk/news/edinburgh…