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Covid-19: what treatments are being investigated?

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1252 (Published 26 March 2020) Cite this as: BMJ 2020;368:m1252

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ADALIMUMAB FOR THE TREATMENT OF PATIENTS WITH COVID-19

Dear Editor,
in her recent excellent report, Elisabeth Mahase reports what treatments are being currently investigated for the treatment of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) (1).
Several treatments have been cited and analysed. I would like to add some information about the possible therapeutic role of adalimumab, a human anti-Tumour Necrosis Factor (TNF) α antibody widely used for the treatment of inflammatory rheumatic diseases and inflammatory bowel diseases, in treating those people.
The potential role of anti- TNFα antibodies in treating COVID 19 people is strictly linked to the pathogenetic mechanisms of this viral infection. We know that SARS-CoV-2 comes into cells after binding to its functional receptor, angiotensin-converting enzyme 2 (ACE2) and causes enhanced TNFα-production and TNFα-converting enzyme (TACE)-dependent shedding of the ectodomain of ACE2, that facilitates viral entry (2). Since this process seems to be strictly coupled to TNFα production, some years ago has been postulated that the use of anti-TNFα antibodies may be effective in reducing both SARS-CoV infection and the consequent organ damage (3). Anti-TNFα antibodies could be able to challenge COVID-19 by two main actions: the classical TNFα inhibition and, more interesting, a down-regulation of ACE 2 expression and shedding, as recently showed in the gut (4). Thus, anti-TNFα antibodies, and adalimumab in particular thanks to its excellent safety profile (5,6), could inhibit these basic mechanisms of COVID-19 (3), and could be potentially useful in managing/preventing COVID-driven pneumonia. As a result, a study evaluating adalimumab injection in COVID-19 patients has recently been registered in order to assess the role of this antibody in treating COVID-19 patients with severe pneumonia (7).

REFERENCES
1) Mahase E. Covid-19: what treatments are being investigated? BMJ 2020;368: m1252
2) Haga S, Yamamoto N, Nakai-Murakami C et al. Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. Proc Natl Acad Sci USA 2008;105: 7809–14
3) Wang W, Ye L, Ye L, Li B, Gao B, Zeng Y, et al. Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res 2007;128:1–8
4) Garg M, Royce SG, Tikellis C et al. Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target? Gut 2019 Aug 13. pii: gutjnl-2019-318512. doi: 10.1136/gutjnl-2019-318512. [Epub ahead of print]
5) Maxwell LJ, Zochling J, Boonen A et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015 Apr 18;(4):CD005468
6) Abbass M, Cepek J, Parker CE, Nguyen TM, MacDonald JK, Feagan BG, Khanna R, Jairath V.
Adalimumab for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2019 Nov 14;2019(11)
7) Chinese Trial Clinical Registry. A randomized, open-label, controlled trial for the efficacy and safety of Adalimumab Injection in the treatment of patients with severe novel coronavirus pneumonia (COVID 19) (ChiCTR2000030089).
http://www.chictr.org.cn/showprojen.aspx?proj=49889

Competing interests: No competing interests

04 April 2020
Antonio Tursi
Chief of the Territorial Gastroenterology Service, Adjunct Professor of Territorial Gastroenterology
Azienda Sanitaria Locale BAT, Andria (BT) - Italy
Via Torino, 49 76123 Andria (BT) – Italy