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

COVID-19 adverse events cancer immune modulation immune suppression

Journal

Ecancermedicalscience
ISSN: 1754-6605
Titre abrégé: Ecancermedicalscience
Pays: England
ID NLM: 101392236

Informations de publication

Date de publication:
2020
Historique:
received: 20 03 2020
entrez: 8 4 2020
pubmed: 8 4 2020
medline: 8 4 2020
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 32256705
doi: 10.3332/ecancer.2020.1022
pii: can-14-1022
pmc: PMC7105343
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

1022

Informations de copyright

© the authors; licensee ecancermedicalscience.

Déclaration de conflit d'intérêts

The authors have no conflicts of interest to declare.

Références

Front Microbiol. 2018 Dec 12;9:3097
pubmed: 30619176
Antiviral Res. 2006 Aug;71(1):53-63
pubmed: 16621037
Antivir Chem Chemother. 2007;18(1):1-11
pubmed: 17354647
J Neurovirol. 2017 Dec;23(6):845-854
pubmed: 28895072
Clin Microbiol Rev. 2015 Apr;28(2):465-522
pubmed: 25810418
Antivir Chem Chemother. 2009;19(4):151-6
pubmed: 19374142
J Med Virol. 2005 Feb;75(2):185-94
pubmed: 15602737
Biochem Biophys Res Commun. 2005 Mar 25;328(4):979-86
pubmed: 15707974
Antiviral Res. 2010 Nov;88(2):160-8
pubmed: 20727913
Microbiol Immunol. 2009 Feb;53(2):75-82
pubmed: 19291090
Bioorg Med Chem. 2003 Oct 15;11(21):4599-613
pubmed: 14527557
Int J Mol Med. 2005 Feb;15(2):323-7
pubmed: 15647850
Curr Med Chem. 2005;12(18):2095-162
pubmed: 16101496
Chest. 1999 Mar;115(3):901-5
pubmed: 10084516
Virol Sin. 2020 Mar 3;:
pubmed: 32125642
Curr Opin Pharmacol. 2012 Aug;12(4):464-70
pubmed: 22819198
J Med Virol. 2020 Mar 17;:
pubmed: 32181911
J Pediatr (Rio J). 2014 Jul-Aug;90(4):370-6
pubmed: 24703819
Respir Investig. 2020 Feb 21;:
pubmed: 32094077
J Infect Dis. 2015 Dec 15;212(12):1904-13
pubmed: 26198719
Virology. 2007 Dec 20;369(2):288-98
pubmed: 17804032
Antivir Ther. 2006;11(8):1021-30
pubmed: 17302372
Zhonghua Nei Ke Za Zhi. 2005 Dec;44(12):890-3
pubmed: 16409721
Virus Res. 2014 May 12;184:44-53
pubmed: 24566223
Cold Spring Harb Perspect Biol. 2014 Sep 04;6(10):a016295
pubmed: 25190079
Lancet. 2020 Feb 15;395(10223):e30-e31
pubmed: 32032529
Lancet Oncol. 2020 Apr;21(4):e181
pubmed: 32142621
Front Microbiol. 2019 Jan 29;10:50
pubmed: 30761102
Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):203-208
pubmed: 32164089
Biosci Trends. 2020 Mar 16;14(1):69-71
pubmed: 31996494
Pediatrics. 2004 Jan;113(1 Pt 1):e7-14
pubmed: 14702488
Infect Immun. 2004 Aug;72(8):4410-5
pubmed: 15271897
J Med Virol. 2006 Apr;78(4):417-24
pubmed: 16482545
Zhonghua Jie He He Hu Xi Za Zhi. 2020 Feb 06;43(0):E005
pubmed: 32026671
J Korean Med Sci. 2016 Nov;31(11):1717-1725
pubmed: 27709848
J Immunol. 2005 Jun 15;174(12):7977-85
pubmed: 15944304
Virus Res. 2012 Apr;165(1):112-7
pubmed: 22349148
Zhonghua Zhong Liu Za Zhi. 2020 Mar 05;42(0):E008
pubmed: 32133833
Cell Mol Immunol. 2004 Jun;1(3):193-8
pubmed: 16219167
Virology. 2009 Dec 20;395(2):210-22
pubmed: 19853271
Expert Rev Anti Infect Ther. 2005 Apr;3(2):251-62
pubmed: 15918782
Clin Biochem Rev. 2004 May;25(2):121-32
pubmed: 18458712
J Antimicrob Chemother. 2008 Sep;62(3):437-41
pubmed: 18565970
Vopr Onkol. 2006;52(4):421-6
pubmed: 17024815
Antimicrob Agents Chemother. 2014 Aug;58(8):4251-2
pubmed: 24867994
J Virol. 2009 Apr;83(7):3039-48
pubmed: 19004938
J Gen Virol. 2014 Mar;95(Pt 3):571-577
pubmed: 24323636
J Biol Regul Homeost Agents. 2019 Feb 4;34(1):
pubmed: 32013309
Virology. 2011 Nov 25;420(2):106-16
pubmed: 21959016
J Med Microbiol. 2003 Aug;52(Pt 8):715-720
pubmed: 12867568
J Virol. 2019 May 29;93(12):
pubmed: 30918074
J Virol. 2018 Oct 29;92(22):
pubmed: 30185587
Zhonghua Jie He He Hu Xi Za Zhi. 2003 Oct;26(10):586-9
pubmed: 14633438
Vet Immunol Immunopathol. 2010 Sep 15;137(1-2):12-9
pubmed: 20466438
Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Feb 26;23(0):E004
pubmed: 32100980
J Antimicrob Chemother. 2016 Dec;71(12):3340-3350
pubmed: 27585965
Annu Rep Med Chem. 2007 Feb 1;41:183-196
pubmed: 19649165
J Infect. 2013 Dec;67(6):606-16
pubmed: 24096239
BMC Infect Dis. 2016 Apr 21;16:174
pubmed: 27097824
Antiviral Res. 2015 Mar;115:9-16
pubmed: 25542975
Lancet Oncol. 2020 Apr;21(4):e180
pubmed: 32142622
Virology. 2007 Sep 1;365(2):324-35
pubmed: 17490702
Lancet. 2003 Jun 14;361(9374):2045-6
pubmed: 12814717
Vet Pathol. 1983 Nov;20(6):653-61
pubmed: 6649336
J Virol. 2008 May;82(9):4420-8
pubmed: 18287230
Infect Dis (Lond). 2020 Feb 18;:1-4
pubmed: 32067542
Blood. 2010 Mar 11;115(10):2088-94
pubmed: 20042728
Lancet Respir Med. 2020 Apr;8(4):e21
pubmed: 32171062
J Med Microbiol. 2017 Sep;66(9):1261-1274
pubmed: 28855003
J Virol. 2007 Nov;81(21):11620-33
pubmed: 17715225
Lancet. 2020 Feb 15;395(10223):507-513
pubmed: 32007143
Expert Rev Anti Infect Ther. 2017 Mar;15(3):269-275
pubmed: 27937060
PLoS One. 2016 Jun 16;11(6):e0157398
pubmed: 27309354
Curr Med Res Opin. 2004 Jan;20(1):39-40
pubmed: 14741070
J Med Chem. 2016 Jul 28;59(14):6595-628
pubmed: 26878082
Clin Infect Dis. 2017 Jun 1;64(11):1532-1539
pubmed: 28329354
Clin Infect Dis. 2004 Oct 1;39(7):1071-5
pubmed: 15472864
Antiviral Res. 2018 Feb;150:155-163
pubmed: 29289665
Clin Exp Immunol. 2004 Apr;136(1):95-103
pubmed: 15030519
Microbes Infect. 2013 Feb;15(2):88-95
pubmed: 23123977
Am J Transplant. 2015 Apr;15(4):1101-4
pubmed: 25716741
Cytokine. 2019 Mar;115:13-23
pubmed: 30616034
Sci Rep. 2017 Jun 22;7(1):4105
pubmed: 28642467
J Formos Med Assoc. 2005 Oct;104(10):715-23
pubmed: 16385373
J Pediatr Hematol Oncol. 2019 May;41(4):e242-e246
pubmed: 30688827
Future Virol. 2011 May;6(5):615-631
pubmed: 21765859
J Biol Regul Homeost Agents. 2020 Mar 14;34(2):
pubmed: 32171193

Auteurs

Beth Russell (B)

Translational Oncology and Urology Research, King's College London, London, UK.
All authors contributed equally.

Charlotte Moss (C)

Translational Oncology and Urology Research, King's College London, London, UK.
All authors contributed equally.

Gincy George (G)

Translational Oncology and Urology Research, King's College London, London, UK.
All authors contributed equally.

Aida Santaolalla (A)

Translational Oncology and Urology Research, King's College London, London, UK.
All authors contributed equally.

Andrew Cope (A)

Guy's and St. Thomas NHS Foundation Trust, London, UK.
Centre for Rheumatic Diseases, King's College London, London, UK.

Sophie Papa (S)

Guy's and St. Thomas NHS Foundation Trust, London, UK.
School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
Both senior authors contributed equally.

Mieke Van Hemelrijck (M)

Translational Oncology and Urology Research, King's College London, London, UK.
Both senior authors contributed equally.

Classifications MeSH