Are NSAIDS contraindicated in patients with 2019 novel Coronavirus infection (Covid-19)?

Despite recent internet reports of the association of non-steroidal anti-inflammatory drugs (NSAIDs) with worsening symptoms among patients with Covid-19 (1), firm clinical evidence to support such claims is currently lacking. However, there are some theoretical reasons why it may still be best to avoid NSAIDs in this condition due to their potential adverse impact on the innate and adaptive immune responses as well as their antipyretic properties (2-9).

 
Blunting of the innate immune response: Certain NSAIDs (eg, ibuprofen, naproxen and celecoxib) inhibit cyclooxygenase enzyme-2 (COX-2) and impair production of several pro-inflammatory cytokines important in fighting infections, such as tumor necrosis factor, interleukin 1 and 6, as well as interferon, an antiviral cytokine (2,6,8). COX-2 has been shown to be important in controlling viral replication in influenza (4). Ibuprofen has been associated with inhibitory effects on a variety of polymorphonuclear functions, including chemotaxis (2).

 
Impact on adaptive immune response: COX-2 inhibition may be associated with impaired neutralizing antibody production (3,4,8). Potential mechanisms include modulation of cytokine expression, nitric-oxide production, and antigen processing/presentation and T lymphocyte activation (3,8).

 
Antipyretic effect: NSAIDs are often given for treatment of fever which is an evolutionary host response to infection. A meta-analysis of animal studies evaluating the impact of antipyretics (including aspirin, NSAIDs, and acetaminophen) in influenza found lower survival in animals treated with antipyretics (9). Longer duration of viral shedding has also been associated with the use of aspirin or acetaminophen in rhinovirus infection (9).

 
Formal epidemiologic and experimental studies are sorely needed to evaluate the safety of NSAIDS in Covid-19.  

 

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References
1. Kolata G. Is ibuprofen really risky for Coronavirus patients? NY Times, March 17, 2020. https://www.nytimes.com/2020/03/17/health/coronavirus-ibuprofen.html
2. Graham NMH, Burrell CJ, Douglas RM, et al. Adverse effects of aspirin, acetaminophen and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers. J Infect Dis 1990;162:1277-1282. https://academic.oup.com/jid/article/162/6/1277/918184
3. Culbreth MJ, Biryunkov S, Shoe JL, et al. The use of analgesics during vaccination with a live attenuated Yersinia pestis vaccine alters the resulting immune response in mice. Vaccines 2019;7, 205; doi:10.3390/vaccines7040205 https://www.mdpi.com/2076-393X/7/4/205
4. Ramos I, Fernandez-Sesma A. Modulating the innate immune response to influenza A virus:potential therapeutic use of anti-inflammatory drugs. Frontiers in Immunology. July 2015. Volume 6. Article 361. https://www.ncbi.nlm.nih.gov/pubmed/26257731
5. Falup-Pecurariu O, Man SC, Neamtu ML, et al. Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine(PHID-CV) co-administered with DTPa-combined vaccines in children:An open-label, randomized, controlled, non-inferiority trial. Human Vaccines & Immunotherapeutics 2017;13: 649-660. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360152/
6. Housby JN, Cahill CM, Chu B, et al. Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine 1999;11:347-58. https://www.ncbi.nlm.nih.gov/pubmed/30186359
7. Agarwal D, Schmader KE, Kossenkov AV, et al. Immune response to influenza vaccination in the elderly is altered by chronic medication use. Immunity & Ageing 2018;15:19. https://www.ncbi.nlm.nih.gov/pubmed/30186359
8. Bancos S, Bernard MP, Topham DJ, et al. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol 2009;258:18-28. https://www.ncbi.nlm.nih.gov/pubmed/19345936
9. Eyers S, Weatherall M, Shirtcliffe P, et al. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis. J R Soc Med 2010;103:403-11. https://www.ncbi.nlm.nih.gov/pubmed/20929891

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Are NSAIDS contraindicated in patients with 2019 novel Coronavirus infection (Covid-19)?

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