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Letter
Use of single-dose tocilizumab for treatment of severe COVID-19 in pregnancy: implications for the timing of live infant vaccines
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  1. Ingrid Burkhardt1,
  2. Elizabeth Whittaker2
  1. 1 Children's Services, Imperial College Healthcare NHS Trust, London, UK
  2. 2 Paediatrics, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Dr Ingrid Burkhardt, Children's Services, Imperial College Healthcare NHS Trust, London, W2 1NY, UK; burkhardt.ingrid{at}gmail.com

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Tocilizumab (a monoclonal antibody inhibiting interleukin-6) is used as standard of care in the treatment of severe COVID-19 pneumonia. This treatment is also prescribed on a case-by-case basis during pregnancy, despite limited data on the impact on the infant immune response.

Data from regular use of monoclonal antibodies during pregnancy are limited, but as they are actively transported across the placenta, concerns regarding immunosuppression in early infancy exist. Therefore, live vaccines are currently contraindicated in infants until 6 months of age in the case of antenatal exposure to monoclonal antibodies.1

The impact of antenatal exposure to anti-tumor necrosis factor (TNF) monoclonal antibodies was recently reviewed2 suggesting that however likely safe before that point, the BCG vaccination should be delayed to 6 months of life. One infant death from disseminated BCG after antenatal exposure to infliximab supports this.3

The use of tocilizumab in pregnancy was recently reviewed,4 highlighting the limited safety data and minimal information on immunological changes in the infant available. Importantly, a randomised controlled trial investigating the vaccine responses to the 23-valent pneumococcal vaccine in patients with rheumatoid arthritis treated with tocilizumab did not show a significant alteration in vaccine response.5 Treatment of severe SARS-CoV-2 infection is usually a single dose of tocilizumab and may therefore have even less effect on the infant’s immune system. Furthermore, the point in pregnancy at which tocilizumab is administered is relevant as the transplacental transport of monoclonal antibodies increases throughout pregnancy.

Given the above uncertainties, there is ongoing debate on whether live vaccines are safe to be administered from birth onwards in this specific situation. The risk of delaying live vaccines to the age of 6 months must be weighed against these uncertainties. Two live vaccines are administered in the first 6 months of life, BCG and rotavirus. Delaying these may place infants at risk of contracting disease. BCG vaccination delivery in the UK has recently changed as screening for severe combined immunodeficiency (SCID) is being piloted and is now targeted and in the community, importantly delayed to after SCID screening results are available, rather than universally in maternity units.

With the ongoing pandemic, there is an urgent need to investigate the effect of a single dose of tocilizumab among other monoclonals at various time points in pregnancy on the infant’s immune system.

Meanwhile, given the lack of safety data and theoretical risk of immunosuppression in the infant, delaying all live vaccines to the age of 6 months in infants who were exposed to tocilizumab during the second or third trimester of pregnancy is recommended. However, in high-risk groups, this may be discussed on a case-by-case basis. All pregnant women with severe COVID-19 should have a tuberculosis (TB) interferon gamma release assay to determine TB risk prior to treatment with monoclonal antibodies. In addition, infants born following tocilizumab exposure in the first trimester should receive clinical review and follow-up, and all monoclonal treatment-exposed infants should be included in research studies. Close follow-up of these infants to ensure catch-up vaccinations is crucial.

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Footnotes

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  • Contributors IB was the primary author. EW reviewed the content and contributed additional valuable input.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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