Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment

Table 1 Clinical evidences of coronavirus disease 2019-induced inflammatory bowel diseases treatment

Ref.	Clinical studies	Model of IBD	Intervention	Duration of treatment	Numbers of animals in intervention group and control group	Outcomes	Adverse effects
Nowak et al[25]	Clinical trial	IBD in COVID-19	-	-	138 treatment naïve IBD patients (cases) and 154 controls	↑ACE2/TMPRSS2 expression; ↑Inflammation	-
Brenner et al[67]	18 yr (with IBD), the Pediatric IBD Porto Group	-	TNF antagonist monotherapy (48%), followed by sulfasalazine/mesalamine (23%)	March 2020-October 2020	Hospitalized cases (n = 14); Outpatient cases (n = 195)	Sulfasalazine/Mesalamine and steroid therapy were associated with increased hospitalization risk and TNF antagonist monotherapy was associated with decreased risk parallel those reported in adult IBD patients. PIBD patients have a relatively low risk of severe COVID-19, even when receiving biologic and/or other immune-suppressive therapies for their IBD	-
Norsa et al[85]	Clinical trial	Crohn disease and Ulcer colitis	Anti-inflammatory (Salicylates); thiopurines or methotrexate; biologics (Infliximab, Adalimumab, Ustekinumab, Vedolizumab, Golimumab); steroids; Other immunosuppressants (Tacrolimus, Cyclosporin, Mofetil Micofenolate)	February 2020-March 2020	Crohn disease = 186; Ulcer colitis = 336	IBD improvement: ↓TNF-α; ↓Inflammation; ↓ACE2/TMPRSS2 expression	-
Mazza et al[86]	Clinical trial	Ulcerative colitis	Methylprednisolone (40 mg/d); prednisone dosage at the time of patient’s death was 25 mg daily	December 2019-February 2020	-	IBD improvement; Improvement in COVID-19 symptoms; ↓Inflammation	-
Tursi et al[87]	Clinical trial	Crohn’s disease	Adalimumab	-	-	Maintain of IBD remission during COVID-19; Managing/preventing COVID-driven pneumonia: ↓TNF-α; ↓Inflammation; ↓ACE2/TMPRSS2 expression	-
Bodini et al[88]	Clinical trial	IBD	Immunosuppressants/biological treatment	3 wk	48 patients	IBD improvement; Improvement in; COVID-19 symptoms	Increase the risk of infection
Tursi et al[89]	Clinical trial	Crohn’s disease	Mesalazine (3 g/d) and Adalimumab 40 mg subcutaneously	-	74 cases	IBD improvement; Improvement in COVID-19 symptoms; ↓TNF-α; ↓Inflammation; ↓ACE2/TMPRSS2 expression	-
Allocca et al[90]	Clinical trial	IBD	Biological treatment	-	162 IBD patients	IBD improvement; Improvement in COVID-19 symptoms	-
Jacobs et al[91]	Clinical trial	Ulcerative colitis	Tofacitinib (10 mg twice daily)	5 mo	-	IBD improvement; Improvement in COVID-19 symptoms	Increase the risk of infection
Gutin et al[69]	Clinical trial	Ulcerative colitis	Biological treatment	February 2020-March 2020	522 patients	IBD improvement; Improvement in COVID-19 symptoms: ↓TNF-α; ↓Inflammation; ↓ACE2/TMPRSS2 expression
Taxonera et al[92]	Clinical trial	Crohn’s disease	Immunomodulatory/biologics	-	n = 12	IBD improvement; Improvement in COVID-19 symptoms; ↓TNF-α; ↓Inflammation; ↓ACE2/TMPRSS2 expression
Allocca et al[93]	Clinical trial	-	Immunosuppressant or biologics	-	n = 15	IBD improvement; Improvement in COVID-19 symptoms; ↓TNF-α; ↓Inflammation	-
Mak et al[94]	Clinical trial	IBD in COVID-19	Thirty (75%) were on 5-Aminosalicylates acid, 15 (37.5%) on immunosuppressants (14 Thiopurine, one Tacrolimus), 11 (27.5%) on corticosteroids and 7 (17.5%) on biologics (3 Infliximab, 1 Adalimumab, 2 Vedolizumab and 1 Ustekinumab)	-	n = 63	IBD improvement; Improvement in COVID-19 symptoms; ↓Inflammation	-
Bardasi and Alvisi[95]	Clinical trial	Crohn’s disease in COVID-19	Subcutaneous administration of 40 mg Adalimumab	6 mo	-	IBD improvement; Improvement in COVID-19 symptoms ↓Inflammation	-
Ashton et al[96]	Clinical trial	IBD in COVID-19	Anti-TNF therapy (Infliximab or Adalimumab)	-	n = 122	IBD improvement; Improvement in COVID-19 symptoms: ↓TNF-α; ↓Inflammation	-

ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane serine protease 2; IBD: Inflammatory bowel diseases; TNF: Tumor necrosis factor.