CTAG: Immune-modulating agents

Download the Position Statement

(V7.0 17 December 2020)

Key messages

  • A subset of patients with COVID-19 may experience an exaggerated hyperinflammatory response
  • COVID-19 associated hyperinflammation predominantly involves the lung however may progress to secondary haemophagocytic lymphohistocytosis (sHLH) which is a systemic and multi-organ condition with significant morbidity and mortality
  • CTAG strongly recommends systemic corticosteroids for patients who fit definitions of WHO-defined severe or critical COVID-19, or in patients who otherwise have a new oxygen requirement
  • CTAG also recommends not to use corticosteroid therapy in patients with WHO-defined non-severe COVID-19 (i.e. the absence of any signs of severe or critical COVID-19).
  • As far as possible, the use of investigative immunomodulatory medicines should be used in the context of a national priority clinical trial. This includes patients treated with remdesivir +/- corticosteroids
  • CTAG acknowledges the recent CAS (Central Alerting System) statement regarding off-label use of tocilizumab in adult patients admitted to the intensive care unit with COVID-19 pneumonia. Published data so far have not demonstrated consistent benefit of tocilizumab in hospitalised patients with COVID-19 outside of the intensive care unit. A recent press release from the REMAP-CAP trial indicated possible benefit in patients admitted to the intensive care unit. CTAG continues to encourage the recruitment of patients into randomised controlled trials, and we do not advocate the use of off-label tocilizumab until further information is made available from REMAP-CAP or other studies in this population.
  • Patients who meet diagnostic criteria for sHLH should be managed within established pathways, guided by a specialist familiar with hyperinflammation
  • IVIG for PIMS-TS should ideally be used within the context of the RECOVERY clinical trial
  • Advice on the appropriate use of remdesivir is available in the CTAG Antivirals position statement
  • Suspected side effects to medicines used in coronavirus treatment should be reported via the Yellow Card COVID-19 reporting site


CTAG acts as a formal advisory group to the Royal College of Physicians and this position statement is endorsed by:

The CTAG Immunomodulators subgroup takes its membership from HLH Across Specialities Collaboration (HASC), a group already formed for management and research of HLH and have expanded remit to include hyper-inflammation associated with COVID-19.


Date publishedVersionAmendment
22 April 20201.0Download PDFNew document
07 May 20201.1Download PDFUpdated evidence summaries in Appendix 1
01 June 20202.0Download PDFUpdated tables of trials and evidence summaries to include new proposed investigational products
16 June 20202.1Download PDFUpdated Table 1, Table 2 and Appendix 1 in line with new available trials, investigational medicines and confirmation where access to remdesivir EAMS is permitted prior to or during trial. Added mechanism of action to Table A1
30 June 20203.0Download PDFIncluded information on dexamethasone following the CMOs letter reporting on preliminary positive results from the RECOVERY trial
10 August 20204.0Download PDFUpdated information for open trials and new emerging evidence
Evidence tables method updated; tables split into those where benefit may exceed risk and where there is inadequate data to recommend use
15 October 20205.0Download PDFUpdated to include new evidence and guidance on corticosteroids from WHO and letter from the CMO office. Additional advice from CTAG to consider dexamethasone in patients with a new oxygen requirement
30 November 20206.0 Download PDFUpdated to provide supporting information on recent REMAP-CAP press release and subsequent NHS England position statement. Evidence table updated with RCT data from tocilizumab trials.
Changes made to streamline position statement by removing introduction and signposting to clinical trials. Information on steroid use in pregnancy updated