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Non-steroidal anti-inflammatory drugs and covid-19

BMJ 2020; 368 doi: (Published 27 March 2020) Cite this as: BMJ 2020;368:m1185

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Rapid Response:

Re: Non-steroidal anti-inflammatory drugs and covid-19; An ambiguous correlation

Dear Editor,

I read carefully Professor Little’s article entitled “Non-steroidal anti-inflammatory drugs and covid-19.”, (1) as well as its rapid response by Dr D’Costa, which are both skeptical regarding the use of NSAIDs in patients with COVID-19. (2) Indeed, there could be several arguments against the use of NSAIDs in patients with COVID-19, with some of them having an immunological basis, since NSAIDs could affect T-cell proliferation and delay the resolution of inflammation, (3) and other arguments focusing on the effect that other NSAID-associated coinciding events, such as cardiovascular complications or kidney injury could have on patients with COVID-19. (1)

However, current scientific evidence does not indicate that patients with mildly symptomatic COVID-19 could be harmed by using NSAIDs. From a pharmacologic perspective, NSAIDs could have a non-predictable effect on inflammation, since prostaglandins like PGE2, PGD2 and prostacyclin (PGI2), that are inhibited by NSAIDs, can both promote and reduce inflammation. On the other hand, it is notable that SARS-CoV can bind directly to the COX-2 promoter and increase its expression, while PGE2 can inhibit replication of SARS-CoV, which is closely related to SARS-CoV-2. (4,5,6) In a very recent study, Gordon et al aimed to study the intracellular protein-protein interactions between SARS-CoV-2 and the human cells in order to identify the human proteins that are occupied by SARS-CoV-2 and to allow for identification of molecules that could be used against those human proteins. (7) Interestingly, Nsp7, a non-structural protein of SARS-CoV-2, was found to interact with PTGES2, a known target of indomethacin, which is a well-known NSAID. This implies that indomethacin could be tested in COVID-19 patients, as it could indirectly affect the activity of Nsp7, and thus, affect the ability of SARS-CoV-2 to multiply intracellularly.

To conclude, even though there are arguments against the use of NSAIDs in COVID-19 patients, one can find several arguments for their use. Thus, only clinical studies could give real-life evidence regarding their effect on COVID-19 patient outcomes.

1. Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;m1185.77
2. D'Costa JJ. Re: Non-steroidal anti-inflammatory drugs and covid-19; An Immune-Modulatory perspective. BMJ 2020;368:m1185
3. Voiriot G, Philippot Q, Elabbadi A, Elbim C, Chalumeau M, Fartoukh M. Risks related to the use of non-steroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med 2019;8:E786.
4. Amici C, Di Caro A, Ciucci A, Chiappa L, Castilletti C, Martella V, Decaro N, Buonavoglia C, Capobianchi MR, Santoro MG. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir Ther. 2006;11(8):1021-30.
5. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-273.
6. Yan X, Hao Q, Mu Y, Timani KA, Ye L, Zhu Y, Wu J. Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein. Int J Biochem Cell Biol. 2006;38(8):1417-28.
7. Gordon DE, Jang GM, Bouhaddou M et al. biorxiv

Competing interests: No competing interests

02 April 2020
Petros Ioannou
Internist, post-doctoral researcher
Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece