Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence

Beth Russell; Charlotte Moss; Gincy George; Aida Santaolalla; Andrew Cope; Sophie Papa; Mieke Van Hemelrijck

doi:10.3332/ecancer.2020.1022

Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence

Ecancermedicalscience. 2020 Mar 27:14:1022. doi: 10.3332/ecancer.2020.1022. eCollection 2020.

Authors

Beth Russell^{1

2}, Charlotte Moss^{1

2}, Gincy George^{1

2}, Aida Santaolalla^{1

2}, Andrew Cope^{3

4}, Sophie Papa^{3

5

6}, Mieke Van Hemelrijck^{1

6}

Affiliations

¹ Translational Oncology and Urology Research, King's College London, London, UK.
² All authors contributed equally.
³ Guy's and St. Thomas NHS Foundation Trust, London, UK.
⁴ Centre for Rheumatic Diseases, King's College London, London, UK.
⁵ School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
⁶ Both senior authors contributed equally.

Abstract

Background: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19.

Methods: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig.

Results: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19.

Conclusion: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

Keywords: COVID-19; adverse events; cancer; immune modulation; immune suppression.

Publication types

Review