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

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

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
Review

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

Beth Russell et al. Ecancermedicalscience. .

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.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

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