New treatments discovered for children with inflammation after COVID-19

Children who develop a rare inflammatory condition after catching COVID-19 have been shown to have shorter hospital stays if treated with newly trialled medicines.

When children catch COVID-19, the illness is usually mild. However, in rare cases, they go on to develop the condition paediatric multisystem inflammatory syndrome (PIMS) a few weeks later.

New research, co-led by Southampton’s Professor Saul Faust, has found the medicines methylprednisolone and tocilizumab can reduce the length of these children’s hospital stay.

This research was conducted as part of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial. It was supported by paediatric nurses from the NIHR Southampton Clinical Research Facility and Biomedical Research Centre.

Southampton’s Dr Chrissie Jones and Dr Katrina Cathie were part of the national working group.

The results are published in The Lancet Child & Adolescent Health.

New condition

PIMS causes inflammation throughout a child's body. It can cause fever, pain, vomiting, headaches or fatigue. In the worst cases, it can lead to heart problems or shock.

The first cases of PIMS associated with COVID-19 appeared during the first few months of the pandemic. It is also sometimes known as multisystem inflammatory syndrome in children (MIS-C).

Similarities were noted between the condition and others such as toxic shock syndrome and Kawasaki disease. This meant patients were initially given immunoglobulin. This is an antibody treatment that can improve the immune system’s ability to fight disease.

First and second treatments

The trial investigated whether two treatments had any effect on how long children with PIMS after COVID-19 needed to stay in hospital.

One was immunoglobulin. The other was methylprednisolone, a type of corticosteroid known to help reduce inflammation. Both were given as ‘first-line’ treatments.

The researchers also evaluated two treatments for children whose symptoms did not improve with the first treatment. These ‘second-line’ treatments were tocilizumab and anakinra.

Both of these are used to reduce inflammation in people with rheumatoid arthritis. RECOVERY previously found tocilizumab can reduce deaths in adults with severe COVID-19.

Recruiting during a pandemic

Overall, 237 children took part. The average age of the children was 9.5 years for the first phase and 9.6 years for the second phase.

In the first phase, 73 children received immunoglobulin, 61 methylprednisolone and 80 usual care. In the second phase, 28 children received tocilizumab, 14 anakinra and 28 usual care.

The researchers looked at how long the children needed to stay in hospital. They also assessed whether they needed heart support medicines and measures of body inflammation. The trial assessed the safety of each of the tested treatments.

To assess how effective the treatments were, the researchers used Bayesian analysis. This is a statistical analysis method. It answers research questions about unknown factors by calculating how likely something is to happen. It also allows researchers to study how medicines work in trials with small numbers of participants.

Richard Haynes, Professor of Renal Medicine and Clinical Trials at Oxford Population Health and the coordinator of the RECOVERY trial, said:

“We are enormously grateful to all of the children, their parents and guardians, and the clinical staff who participated in the trial. They have not only enabled the discovery of two treatments that may benefit future patients, but they have also helped us to demonstrate that it is feasible to recruit children into trials during a pandemic to generate reliable evidence for effective treatments.”

Shorter hospital stays

The researchers found two of the treatments can reduce how long these children stay in hospital. These were methylprednisolone as a first-line treatment, and tocilizumab as a second-line treatment.

In the first phase of the trial, children who received usual care stayed in hospital for an average of 7.6 days. For children who received immunoglobulin, it was 7.4 days. For children given methylprednisolone, it was 6.9 days.

In the second phase, children who received usual care stayed in hospital for an average of 9.9 days. C For children who received anakinra, it was 8.5 days. For children given tocilizumab, it was 6.6 days.

Both effective treatments were associated with an increased use of heart support medicines compared to usual care.

There were few harmful safety outcomes. Two persistent coronary artery aneurysms (a problem with a blood vessel in the heart) were reported in the usual care group in the first phase.

Saul Faust, Professor of Paediatric Immunology and Infectious Diseases at the University of Southampton and lead paediatric author of the study, said:

“With the help of patients and clinicians in the UK, we now know that treatment with methylprednisolone in the first instance and tocilizumab when inflammation is persistent can be beneficial in reducing inflammation and the length of hospital stays for children with paediatric multisystem inflammatory syndrome associated with COVID-19.

“We also found that treatment with immunoglobulin and anakinra have no beneficial effect on these outcomes. We recommend that the trial results be used to inform updates of clinical guidelines.”