ASCIA Position Statement: Specific Treatments for COVID-19

At present, there are several pharmacological therapies that are being used for treatment of the COVID-19 respiratory disease that is caused by the novel coronavirus SARS-CoV-2. There are no known preventative therapies currently available.

ASCIA acknowledges the urgent need for effective therapies for the prevention and treatment of COVID-19. As the situation regularly changes this document is reviewed and updated as required.

Content last updated August 2020.

pdfASCIA HP Position Statement COVID-19 Treatments 2020 August Update167.35 KB

Pharmacological treatments for COVID-19 can be divided into two classes:

  • Antiviral therapies -
    • Pharmacological, e.g. remdesivir, (TGA approved for COVID-19).
    • Biological, e.g. convalescent serum (see ASCIA Position Statement on Immunoglobulin Therapies for COVID-19).
  • Immunomodulatory therapies -
    • Corticosteroids, e.g. dexamethasone (see below).
    • Anti-interleukin-6 (Anti-IL6), e.g. tocilizumab, siltuximab, and sarilumab.
    • Anti-interleukin 1 (Anti-IL1), e.g. anakinra.
    • Intravenous Immunoglobulin G (IVIg) - NOT recommended (see ASCIA Position Statement on Immunoglobulin Therapies for COVID-19 and recommendation 5 in this Statement).

ASCIA is aware that many clinical trials are underway in Australia and internationally, and a number of resources are available to access details, including the following websites:

The aim of these trials is to provide clinical evidence for safety and efficacy of medications for the prevention and/or treatment of COVID-19. 

In the interim ASCIA does not usually recommend the off-label use of medications for the prevention or treatment of COVID-19 outside of these trials, for the following reasons:

  • Uncertain benefits.
  • Potential risk of harm.
  • Impact that inappropriate use of these medications has on continuity of supply for patients with immune diseases for which these medications are established treatments.

Whilst ASCIA recommends that experimental therapies for COVID-19 should be administered in the context of a clinical trial where available, it is recognised that circumstances may arise where this is not possible. ASCIA advises that treatments that lack robust supportive evidence of safety and efficacy in this setting should be considered with appropriate expert consultation.

The role of immunomodulation in COVID-19

Current management of COVID-19 is largely supportive, with respiratory support in cases that develop COVID-19 related acute respiratory distress syndrome (ARDS). However, despite usual ventilation strategies, mortality remains high1. There are also reports of the ARDS being unusual and not responding to usual methods of ventilation2.  

Alternative hypotheses have been suggested to explain this phenomenon.  Largely this is biologically explained by a cytokine storm syndrome, otherwise known as hyperinflammation3.

Corticosteroids

In July 2020 investigators from a large UK trial published a preliminary report showing survival benefits for patients receiving supplemental oxygen when treated with dexamethasone.4

ASCIA supports the administration of dexamethasone to adults with COVID-19 receiving supplemental oxygen.

IL-6 blockade

Based on the understanding of the possible contribution a cytokine storm syndrome to the increased mortality in COVID-19, IL-6 blockade has been considered as a potential therapy. IL-6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine.

Tocilizumab (Actemra) is an inhibitory IL-6 receptor monoclonal antibody which has an established role for the treatment of life-threatening cytokine release syndrome caused by chimeric antigen receptor (CAR) T-cell therapy5.

A number of retrospective studies have been performed evaluating use of tocilizumab in COVID-19 with mixed results. ASCIA strongly supports enrolment of patients with COVID-19 in to clinical trials to better understand the role of immunomodulatory therapy such as tocilizumab in patients with COVID-19, and determine whether there is a subset of patients with cytokine storm/hyperinflammation who may benefit from this type of therapy.

Recommendations

  1. ASCIA strongly endorses a collaborative, multidisciplinary approach to management of COVID-19.
  2. ASCIA recommends the use of therapies such as remdesivir (TGA approved for COVID-19) and dexamethasone, in appropriate patients with COVID-19.
  3. ASCIA does not currently recommend the use of immunomodulation such as Tocilizumab or Anakinra outside of clinical trials. However, there may be exceptional circumstances in which administration of this agent may be considered, with appropriate expert consultation. Clinicians must balance the potential risks and benefits for any individual patient.
  4. ASCIA recommends against the use of IVIg until data emerges of a potential benefit. However, IVIg as an Immunomodulatory therapy may have a role in the treatment of rarer SARS-CoV2 associated complications such as PIMS-TS or MIS-C.13, 14

Further information

The situation regarding COVID-19 is rapidly changing, so it important to monitor information from ASCIA, other organisations, and Australian and New Zealand governments, that are available on the ASCIA COVID-19 webpage www.allergy.org.au/members/covid-19, which is reviewed daily and updated as required.

References

  1. Wu, C. et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med, (2020). https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2763184 
  2. Gattinoni, L. et al. Covid-19 Does not Lead to a ‘Typical’ Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med., (2020).  https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE
  3. Mehta, P. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 395, 1033–1034 (2020). https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext).
  4. The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. NEJM, 2020. https://www.nejm.org/doi/10.1056/NEJMoa2021436
  5. Le, R. Q. et al. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. Oncologist, 23, 943–947 (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156173/
  6. Giavridis, T. et al. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med, 24, 731–738 (2018). https://www.nature.com/articles/s41591-018-0041-7
  7. Ascierto, P. A. et al. Insights from immuno-oncology: the Society for Immunotherapy of Cancer Statement on access to IL-6-targeting therapies for COVID-19. J Immunother Cancer, 8, (2020). https://www.sitcancer.org/research/covid-19-resources/il-6-editorial
  8. Michot, J.-M. et al. Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report. Ann Oncol., (2020). https://www.annalsofoncology.org/article/S0923-7534(20)36387-0/pdf 
  9. Xu, X. et al. Effective treatment of severe COVID-19 patients with tocilizumab. PNAS, 2020. https://www.pnas.org/content/117/20/10970
  10. Morrison et al, Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab. J Autoimmun., 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332925/
  11. Hill, J. A. et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood, 131, 121–13 (2018). https://www.annalsofoncology.org/article/S0923-7534(20)36387-0/pdf
  12. Pawar, A. et al. Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study. Ann Rheum Dis., 78, 456–464 (2019). http://dx.doi.org/10.1136/annrheumdis-2018-214367 
  13. Feldstein, L. R et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. NEJM, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2021680
  14. Davies, P et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. The Lancet Child & Adolescent Health, July 2020. https://www.sciencedirect.com/science/article/pii/S2352464220302157

© ASCIA 2020

ASCIA is the peak professional body of clinical immunology/allergy specialists in Australia and New Zealand.

ASCIA resources are based on published literature and expert review, however, they are not intended to replace medical advice.

The content of ASCIA resources is not influenced by any commercial organisations.

For more information go to www.allergy.org.au

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