June 16, 2021

expert reaction to study looking at treatments for COVID-19 complications in children

A study published in the New England Journal of Medicine (NEJM) looks at treatment of multisystem inflammatory syndrome in children (MIS-C) after exposure to COVID-19.

Prof Athimalaipet Ramanan, Honorary Professor, Bristol Medical School, University of Bristol:

“This is an important result which shows that in MIS-C (a rare but serious complication in children after exposure to COVID) steroids are potentially as effective as intravenous immunoglobulin (IVIG).

“MIS-C is a growing problem facing children in countries such as India following the second wave. IVIG is expensive and in short supply whilst steroids are cheap, safe and well-tolerated in children.

“Not being a randomised controlled trial, this study suffers from a lack of rigour in making firm conclusions. However, the paediatric arm of the RECOVERY study is specifically targeting this question and will hopefully provide more conclusive evidence soon.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This study is not randomised and only provides weak evidence. It is certainly a study compatible with some benefit but it is certainly possible there is no benefit to corticosteroids and it is also compatible with harm.

“It does not give clear answers and even had the results been more favourable, its design would inevitably mean that conclusions would be uncertain.

“One can understand that clinicians want to do their best when there is limited evidence about treatments, but this is exactly the situation when a randomised trial is both necessary and justified. The RECOVERY and similar trials have shown that this is the way to obtain reliable evidence on treatments for Covid.

“It seems that the barriers to treating patients in a randomised trial can be much higher than simply giving them a treatment for which there is no evidence but not randomising them. We await clear answers from randomised trials.”

Prof Saul Faust, Professor of Paediatric Immunology & Infectious Diseases, University of Southampton & Director of the NIHR Southampton Clinical Research Facility, said:

“These are very interesting data from a very large cohort that suggest similar conclusions to a French cohort previously reported in JAMA.

“However, as there is no randomisation, the study does not answer the key question globally, which is whether corticosteroids could be used instead of immunoglobulin for the first line treatment of multisystem inflammatory syndrome associate with COVID-19 in children. This is a critical question for paediatricians globally as immunoglobulin is both very expensive compared to steroids and very difficult to access in many parts of the world. Intravenous immunoglobulin preparations are also subject to severe supply chain issues in the UK, although access is not currently restricted for the treatment of this condition.

“The UK RECOVERY trial is currently the only global randomised controlled trial (RCT) randomising children to intravenous immunoglobulin and high dose corticosteroids for paediatric inflammatory syndrome and hopes to answer this question. The paediatric arms of RECOVERY have recruited 281 children to date.

“Colleagues in Switzerland have also recently been able to open a trial replicating the RECOVERY protocol to inform a future metanalysis, and the Swiss team hope to also be able to open their trial in sites in Latin America, South Africa and Nepal.

‘Treatment of Multisystem Inflammatory Syndrome in Children’ by McArdle et al was published in the New England Journal of Medicine at 22:00 UK time on Wednesday 16^th June.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Athimalaipet Ramanan: “Sits in the paediatric steering committee of RECOVERY trial and has led/participated trials of Tocilizumab and Baricitinib in adults and children with COVID-19.”

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.  I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”

Prof Saul Faust: “Chair, UK RECOVERY Trial Paediatric working group.”