P35 Remdesivir in a pre-term neonate – was it worth it?
Authors: Kafka Susan 
Published: April 2023

Background Situation

On day 24 of life, a pre-term neonate (GA at birth 31+2 weeks) with achondroplasia tested SARS-CoV-2 positive on PCR. The patient was ventilated for increasing oxygen requirements, eventually necessitating transfer to the regional PICU. Meeting the clinical case definition for severe acute respiratory COVID-19, the patient was initiated on hydrocortisone 0.5 mg/kg BD as per Scottish Paediatric Consensus Guidelines for COVID-19.1Respiratory decline, with bilateral consolidation on chest X-Ray led to oscillation on day 27 of life. An MDT was set up to consider next steps. There is a paucity of evidence for managing severe acute respiratory COVID-19 in this age group. The MDT considered unlicensed use of tocilizumab (TOC) and remdesivir (RDV) as potential therapies. Evidence on the utility of RDV in severe acute COVID-19 is conflicting.2 3TOC use in <18 years is extrapolated from adult data, with sparse dosing information in <1 years. CRP remained below adult threshold (44). Concern regarding immunosuppressive effect of TOC was raised as secondary bacterial infection had not been excluded. On balance, the MDT concluded RDV be offered as the ‘next step’ treatment option. Renal and liver function were normal pre-RDV (ALT 19, AST 57), however within 48hour (2 doses) of RDV, transaminases had increased to >5x ULN (ALT 354, AST 873). Clinical status remained otherwise stable, and no other changes to medication were identified, thus the decision was made to withdraw RDV as the likely cause. 48 hours post withdrawal transaminases has normalised. The patient clinically improved over the next 5 days and was extubated ~7 days later.

Clinical Contribution

Pharmacy played a significant role in the MDT, and were heavily involved in all risk:benefit decision making. Initial literature searches were conducted to establish current data on both TOC and RDV in this age group. A Phase 2/3 trial protocol evaluating RDV safety, tolerability and pK in COVID-19 patients from birth-18 years was obtained to further guide decision making. Assessment of treatment eligibility based on UK CAS alert and the Phase 2/3 study was undertaken, along with assessment of baseline clinical parameters. On MDT decision to treat, Pharmacy supported in the ULM application process (internal and Gilead compassionate access scheme) and advised on dosing, administration and monitoring. Pharmacy played a pivotal role in monitoring and recognition of adverse events. On identifying rapidly developing transaminitis, a full review was undertaken to determine RDV as a likely causative agent to support the decision to withdraw treatment. A Yellow Card was completed.

Conclusion

Despite withdrawal of RDV after only 2 days, the patient clinically improved and was extubated and discharged a short time after, raising the question as to whether RDV offered any clinical benefit in this case. Managing severe acute COVID-19 in neonates presents a significant challenge for clinical teams. There remains a paucity of evidence in this age group.4Treatment decisions are made on a case-by-case basis, however outcomes are rarely published. More evidence is required before significant conclusions can be drawn about the utility or safety profile of RDV in neonates.

References

Pollock L, McLellan K. ‘Scottish Paediatric Consensus Treatment Guidelines for COVID-19 and related conditions’, produced by Scottish Hyperinflammatory MDT; NHS GG&C Clinical Guidelines; 2020, V3.

Beigel J, Tomashek K, Dodd L,et al. Remdesivir for the treatment of COVID-19- final report.New England Journal of Medicine2020;383:1813–1826.

Hongchao P, Peto R, Henao-Restrepo AM,et al. Repurposed antiviral drugs for COVID-19 – interim WHO solidarity trail results (WHO Solidarity Trail Consortium).New England Journal of Medicine2021;384:497–511.

Swann O, Holden K, Turtle L,et al. Clinical characteristics of children and young people admitted to hospital with COVID-19 in the United Kingdom: prospective multicentre observational cohort study.BMJ2020;370:m3249.