To the Editor Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease-19 or “COVID-19,” is currently implicated in a global pandemic. As of April 19, 2020, there have been 2,241,778 confirmed cases worldwide.1 Although the pathophysiology is still being elucidated, there is evidence of hyperactivation of effector T cells and excessive release of inflammatory cytokines, particularly interleukin (IL)-6, leading to cytokine release syndrome and end organ damage.2 Current proposed treatments include tocilizumab, an IL-6 receptor antagonist, and corticosteroids. We present a brief case of a patient with COVID-19 who subsequently developed a gastrointestinal (GI) perforation, which we believe was due to the underlying disease process itself, or treatment modalities given. A 73-year-old man, with a prior history of coronary artery disease, peripheral vascular disease, diabetes, chronic kidney disease, and obesity (with a body mass index of 32), presented to the hospital with fever, cough, and shortness of breath. On presentation, he was febrile and hypoxemic requiring a non-rebreather at 15 L/min. Initial blood work showed a white blood cell count of 22.0 × 103/μL, hemoglobin of 11.6 g/dL, hematocrit of 34%, platelet count of 257 × 103/μL, Na of 132 mEq/L, K of 4.6 mEq/L, Cl of 104 mEq/L, CO2 of 10 mEq/L, BUN of 92 mg/dL, and Cr of 4.0 mg/dL (with a known baseline of 1.8 mg/dL). Chest x-ray revealed diffuse, patchy, bilateral lung opacities. Nasal polymerase chain reaction swab for SARS-CoV-2 was positive. On hospital day 2, he required intubation and mechanical ventilation. Also, on hospital day 2, he received tocilizumab, 400 mg intravenously. Because of the failure of ventilator weaning, he underwent a tracheostomy on hospital day 9. He received intravenous methylprednisolone, at a total daily dose of 100 mg, between hospital days 11 and 16, given his respiratory status had not significantly improved. By hospital day 16, he was still requiring full ventilatory support via his tracheostomy. He otherwise did not appear to have any other specific complaints. That day, a routine chest x-ray showed substantial subphrenic air likely representing a GI perforation, which was confirmed on a lateral decubitus film (Fig. 1). He was evaluated by surgery, and exploratory surgery was discussed; however, due to his high-risk surgical status, a conservative approach was chosen. He was followed up with serial abdominal examinations and given intravenous antibiotics. Six weeks later, he continues to do well and has since been decannulated. On review of his case, it was felt that either his underlying viral infection or his treatments (tocilizumab and/or corticosteroids) were the likely etiology of his perforation.FIGURE 1: Lateral abdominal decubitus XR with abdominal free air.SARS-CoV-2 represents a significant and ongoing cause of morbidity and mortality worldwide. This viral infection often presents with fever, cough, and shortness of breath, though GI symptoms, such as nausea, vomiting, abdominal pain, and diarrhea, are also common.3 Angiotensin-converting enzyme-2 receptor is a major functional receptor of SARS-CoV-2 and is expressed on the surface cells of the digestive tract, likely leading to the GI symptoms seen in the disease.3 To date, there have been no reports of GI perforation specifically attributed to SARS-CoV-2, though given the widespread expression of angiotensin-converting enzyme-2 receptors in the digestive tract, it is plausible that viral binding can lead to disruption of mucosal cell integrity. However, both tocilizumab and corticosteroids have been implicated in general GI perforation. Tocilizumab is associated with a small risk of GI perforation. On review of patients taking tocilizumab for rheumatoid arthritis, a GI perforation rate of 1.55 to 1.9 per 1000 patient years was seen.4 Mesenteric adipose tissue is both maintained by and a major source of IL-6, and although IL-6 activity leads to transmural inflammation of the bowel, the local accumulation of the adipose tissue itself can be protective against perforation. Thus, the inhibition of IL-6 by tocilizumab and the resulting breakdown of mesenteric fat are possible mechanisms of perforation.5,6 The IL-6 and cytokine release syndrome may have led to mucosal breakdown in our patient, and as he had a body mass index of 32 and likely increased mesenteric fat, he could have been more susceptible to tocilizumab's actions as well. Corticosteroids are also well known to lead to GI perforation. Corticosteroids can impair the body's ability to contain microperforations via anti-inflammatory properties, and also inhibit prostaglandin production, which has an important role in maintaining colonic mucosal integrity via secretion of mucin and bicarbonate.7 Ultimately, though the etiology of our patient's GI perforation is unclear, we hypothesize that it must be related to either his underlying disease process or is a consequence of treatment. Clinicians must remain aware of this potential complication when caring for COVID-19 patients. Lydia M. Winnicka, MDMangalore A. Shenoy, MD Department of Pulmonary and Critical Care Medicine NYU Winthrop Hospital, Mineola, NY [email protected]
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Aug 6, 2020
Mitsuhiro Tachibana + 5
Open Access
