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Anti-tumor necrosis factor-alpha (anti-TNF-α) agents have been suggested as being favorable [1] and a potential treatment for coronavirus disease of 2019 (COVID-19) [2]. High serum levels of TNF-α upon admission have been associated with a severe COVID-19 infection [3]. From the literature studying sepsis, non-related to COVID-19, a previous meta-analysis had found an improved survival, in particular 28-day all-cause mortality, with monoclonal anti-TNF antibodies [4]. In trials of acute inflammation, such as steroidrefractory and severe ulcerative colitis (UC), anti-TNF agents were shown to have a favorable adverse event profile, in addition to inducing higher remission rates and improving the percentage of colon-salvage [5-7]. The experience of IBD patients infected with COVID-19 has been reported through the SECURE-IBD database. As of July 13, 2020, 15% of the patients on anti-TNF therapy required hospitalization, with 2% requiring intensive care and 1% succumbing to the disease [8]. Patients treated with steroids or sulfasalazine/mesalamine required intensive care in 15% and 8% of the cases, respectively, and had a mortality of 9% and 6% [8]. It appears that in the setting of maintenance therapy with anti-TNF antibodies, COVID-19 infections are associated with less serious complications as compared to other maintenance modalities. How an anti-TNF-α therapy could work for patients who had not been on treatment at the onset of their COVID-19 infection has yet to be defined. Furthermore, important differences exist between the study populations of IBD trials and COVID-19 patients. IBD trials typically exclude patients with severe uncontrolled infections and those with heart failure [6]. Severe COVID-19 infections would have likely been excluded from participation in these trials. Furthermore, the age group studied in these IBD trials tends to be in the 20-40-year-old range [7], much younger than the critically ill patients with a severe COVID-19 infection [9]. Although graded as severe, the disease burden of UC in such studies is usually confined to the intestine, without the outright systemic sepsis seen in severe COVID-19 cases. The cumulative evidence in the literature has also been inconsistent regarding the safety profile for infectious adverse events with anti-TNF-α therapies in IBD. When compared to placebo, meta-analysis has found that UC patients treated with anti-TNF agents had increased long-term risks of opportunistic and of serious infections requiring intravenous antibiotics or hospitalization, or causing death [10]. A higher risk of serious

Anti-tumor necrosis factor agents and COVID-19: A word of caution