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Immune-Based Therapy Under Evaluation for Treatment of COVID-19

Last Updated: May 12, 2020

Summary Recommendations
Summary Recommendations

There are no Food and Drug Administration-approved drugs for the treatment of COVID-19. Although reports have appeared in the medical literature and the lay press have claimed that patients with COVID-19 have been successfully treated with a variety of agents, definitive clinical trial data are needed to identify safe and effective treatments for this disease. Recommended clinical management of patients with COVID-19 includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated. As in the management of any disease, treatment decisions ultimately reside with the patient and their health care provider.

Immune-Based Therapy:

  • There are insufficient data to recommend either for or against the use of COVID-19 convalescent plasma or SARS-CoV-2 immune globulins for the treatment of COVID-19 (AIII).
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial (AIII). This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.
  • There are insufficient data to recommend either for or against the use of the following agents for the treatment of COVID-19 (AIII):
    • Interleukin-1 inhibitors (e.g., anakinra)
    • Interleukin-6 inhibitors (e.g., sarilumab, siltuximab, tocilizumab)
  • Except in the context of a clinical trial, the Panel recommends against the use of other immunomodulators, such as:
    • Interferons (AIII), because of the lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity.
    • Janus kinase inhibitors (e.g., baricitinib) (AIII), because of their broad immunosuppressive effect.
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion

Several immune-based therapies that are directed at modifying the course of COVID-19 are currently under investigation or are being used off-label. These agents may target the virus (e.g., convalescent plasma) or modulate the immune response (e.g., interleukin-1 [IL-1] or interleukin-6 [IL-6] inhibitors).

For more information on host modifiers and immunotherapy that are under evaluation for COVID-19, see Tables 3a and 3b.

Interleukin-1 and Interleukin-6 Inhibitors and Other Immunomodulators

The cytokine profiles of serum from some patients with moderate to severe COVID-19 overlap with those seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (sHLH).1 MAS is characterized by hyperinflammation and manifests as fever, elevated ferritin levels, and pulmonary involvement, with a spectrum of presentation that includes sHLH.2 Viruses are known triggers of MAS/sHLH, and high ferritin levels are associated with both MAS and mortality in patients with COVID-19.3,4 Endogenous IL-1, a proinflammatory cytokine, potently induces IL-6 in monocytes and macrophages and is elevated in patients with COVID-19, MAS, and other conditions, such as severe chimeric antigen receptor T cell-mediated cytokine release syndrome.5 The Janus kinase (JAK) family of enzymes regulate signal transduction in immune cells, and JAK inhibitors play a major role in inhibiting and blocking cytokine release. IL-6 and IL-1 blockades and JAK inhibition, both of which have been proposed as an approach to treat the systemic inflammation associated with severe COVID-19 illness,6 are reviewed in their respective pages.

References

  1. Pedersen SF, Ho Y. SARS-CoV-2: A storm is raging. The Journal of Clinical Investigation. 2020. [In press]. Available at: https://www.jci.org/articles/view/137647.
  2. Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014;383(9927):1503-1516. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24290661.
  3. Seguin A, Galicier L, Boutboul D, Lemiale V, Azoulay E. Pulmonary involvement in patients with hemophagocytic lymphohistiocytosis. Chest. 2016;149(5):1294-1301. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26836913.
  4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31986264.
  5. Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior Phase III trial. Crit Care Med. 2016;44(2):275-281. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26584195.
  6. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32192578.