Key statements/findings	Level of evidencea
Palivizumab
Currently, the only product licensed for prophylaxis against RSV	Level 1 studies: 5
Preterm infants < 35 wGA: 68% (range 64–100%) reduction in RSVH (absolute risk reduction: 0.2–14.7%)	Risk of biasb: low Qualityc: high
Children with CLD/BPD: 65% (range 38–72%) reduction in RSVH (absolute risk reduction: 4.9–14.2%)
Children with CHD: 53% (range 45–58%) reduction in RSVH (absolute risk reduction: 4.4–4.6%)
Limited data in other comorbidities
Significantly reduced subsequent wheezing episodes	Level 1 studies: 1 Risk of biasb: low Qualityc: high
Ribavirin
Licensed for treatment of severe RSV infection	Level 1 studies: 4
Lack of evidence supporting its efficacy and concerns over toxicity	Risk of biasb: unclear Qualityc: low
Strongest evidence in immunocompromised infants
Future therapies
There are currently around 28 RSV vaccines in preclinical development and WHO estimates the availability of an RSV vaccine within 5–10 years	N/A
Nanoparticle and subunit vaccines are the most promising for pregnant women, whereas live-attenuated, vector-based and subunit vaccines are optimal for the pediatric population	N/A
Several new antibodies targeting the RSV fusion (F) protein are showing promise (e.g. MEI8897) and entering phase 3 trials	N/A
Recent efforts to develop RSV antiviral drugs have focused primarily on fusion inhibitors or virus gene silencing; a number are in development and could become available for clinical use within a few years	N/A
Key areas for research 1. Currently approved therapies More up-to-date research and published, prospective RCTs are needed to determine:  The effectiveness of palivizumab in reducing RSVH and improving outcomes in children with underlying medical conditions, such as Down syndrome, cystic fibrosis, congenital airway anomalies, immunocompromising or neuromuscular disease  The ultimate impact of palivizumab on longer-term sequelae, such as recurrent wheezing 2. Future therapies for prevention and treatment Continued research is needed on:  Receptive strategies, such as pre- versus post-natal prophylaxis  Establishing whether there is a causal link between RSV infection and asthma, possibly via a follow-on to a phase 3 vaccine or prophylaxis trial  The optimal timing of therapy with antiviral drugs Whether the combination of antiviral drugs and immunomodulatory therapies might improve outcomes, as suggested by Prince et al. [216]

N/A not applicable, RSVH respiratory syncytial virus hospitalization, RCT randomized controlled trial

^aCEBM) Levels of Evidence [31, 32] where Level 1 = RCTs

^bCochrane risk of bias assessment [34], where low = average of 5/7 domains assessed as low risk of bias, high = average of 5/7 domains assessed as high risk of bias, and unclear for scores inbetween (see online supplementary material for full breakdown)

^cAverage Jadad score [33], where ≥ 3 = high quality (see online supplementary material for full breakdown)