Introduction: Prevalence of gastrointestinal symptoms in patients infected with SARS-CoV-2 virus is 6.8% - 61.3%. Most common symptoms include diarrhea (8.1% - 33.7%), nausea/vomiting (1.5% - 26.4%), anorexia (12.1% - 26.4%), and abdominal pain (0 – 14.5%). Management involves treating respiratory manifestation of COVID-19, treating co-existing infections, and supportive care. We present a case of severe hemorrhagic enterocolitis managed with a biologic. Case Description/Methods: 47-year-old woman with COVID-19 pneumonia was admitted for extracorporeal membrane oxygenation. She developed copious amounts of watery diarrhea followed by bloody diarrhea. Stool work-up was negative for infectious causes of diarrhea. Colonoscopy revealed diffusely erythematous and friable mucosa with epithelial loss involving the entire colon and distal ileum. She was managed with rectal tube, blood transfusions, parenteral nutrition. Despite escalating doses of numerous anti-diarrheals, topical as well as systemic steroids, copious volumes of bloody diarrhea continued. Repeat colonoscopic biopsies demonstrated CMV-like inclusions with borderline elevated serologic titers. Despite successful eradication of CMV with prolonged courses of ganciclovir and foscarnet, hemorrhagic diarrhea continued. Several upper and lower endoscopies suggested worsening mucosal erythema and friability, predominantly involving small bowel and colon. Given COVID enterocolitis refractory to all the above treatments, induction therapy with a biologic was considered to treat possible de novo inflammatory bowel disease (IBD) versus immune mediated effects of COVID-19 enterocolitis. After induction doses of Ustekinumab, an IL-12 and IL-23 inhibitor, volume of diarrhea reduced and bloody diarrhea resolved, facilitating removal of rectal tube, resumption of oral nutrition, discontinuation of anti-diarrheals. Patient was discharged on maintenance Ustekinumab. Follow-up endoscopic evaluation demonstrated mucosal healing, with epithelial regeneration and chronic inflammatory changes of crypt distortion. Discussion: SARS-CoV-2 infection triggered an inflammatory cascade in the intestinal tract leading to altered or increased immune response, probably on a background of genetic predisposition, in our patient. Initiation of Ustekinumab, IL-23/IL-12 inhibitor, likely resulted in suppression of the severe systemic inflammatory response, resulting in clinical, endoscopic and pathological response.Figure 1.: (a) demonstrates endoscopic appearance of transverse colon with erythema, friability and hemorrhages prior to treatment with biologic (b) demonstrates epithelial denudation with minimal acute inflammation in colonic mucosa prior to treatment with biologic (c) demonstrates endoscopic appearance of transverse colon with resolving erythema after treatment with biologic (d) demonstrates chronic inflammatory changes with crypt architectural distortion and pyloric gland metaplasia after induction of remission with biologic, many months after initial presentation.