key: cord-1047050-53byihmi
authors: Hajifathalian, Kaveh; Krisko, Tibor; Mehta, Amit; Kumar, Sonal; Schwartz, Robert; Fortune, Brett; Sharaiha, Reem; Kaplan, Alyson; Gonzalez, Susana; Skaf, Daniel; Ang, Bryan; Choi, Anthony; Wong, Angela; Aboubakr, Aiya; Niec, Rachel; Rohan, Elizabeth; Speiser, Julia; Ying, Xiaohan; Pan, Yushan; Ianelli, Mallory; Rajan, Anjana; Ravishankar, Arjun; Tewani, Sunena; Dawod, Enad; Dawod, Qais; Rosenblatt, Russell; Carr-Locke, David; Shah, Shawn; Mahadev, Srihari; Wan, David; Crawford, Carl; Sholle, Evan; Brown, Robert; Cohen, David
title: Gastrointestinal and Hepatic Manifestations of 2019 Novel Coronavirus Disease in a Large Cohort of Infected Patients From New York: Clinical Implications.
date: 2020-05-08
journal: Gastroenterology
DOI: 10.1053/j.gastro.2020.05.010
sha: ce971985a2b3f4058d7bfd9a4d7e0be67815f804
doc_id: 1047050
cord_uid: 53byihmi

nan

Recent reports suggest that prevalence of gastrointestinal and hepatic manifestations in COVID-19 are higher than initially reported, particularly in Western populations. New York City has arguably been the epicenter of the COVID-19 pandemic in the United States, creating a unique opportunity to further the understanding of this disease. Our objectives were to investigate the prevalence of GI and hepatic manifestations of COVID-19 patients, and explore their effect on the clinical outcomes in these patients.

This is a retrospective review of consecutive adult patients (age≥18) with a positive real-time reverse-transcription polymerase chain reaction for SARS-CoV-2 recorded between March 4 and April 9, 2020 at one of our two hospitals in Manhattan (an academic tertiary referral center and a smaller community hospital), USA. The history, laboratory data, and outcome measures were extracted from patients' medical records, using an structured abstraction tool. All vital signs and lab data were collected at presentation. "GI manifestation" was defined as presence of nausea, vomiting, diarrhea, or abdominal pain. Patients were considered to have indication of liver injury at presentation if they had elevated ALT, AST, total bilirubin, or alkaline phosphatase. The primary clinical outcome for admitted patients was defined as a composite of ICU admission or death (details of methods is available in supplementary material).

1059 patients diagnosed with COVID-19 with a mean age of 61(SD 18) years (58% male) were included in the study (Table 1) . At presentation, 22% of patients had diarrhea, 7% had abdominal pain, and 16% and 9% had nausea and vomiting, respectively. 33% of patients had at least one GI manifestation. At presentation, patients had a mean ALT of 50 (65), mean AST 60 (79) U/L, mean total bilirubin 0.7 (0.6) mg/dL, and mean alkaline phosphatase of 88 (74) U/L. 62% of the patients had biochemical evidence of liver injury with at least one of their liver enzymes elevated.

In multivariable analysis of the effect of gender, age, pre-existing immunosuppression, IBD or chronic liver disease on presence of GI manifestation or liver injury, female patients (OR=1.30, 95%CI 1.01-1.69, p=0.048), and patients with chronic liver disease (OR=2.18, 95%CI 1.08-4.44, p=0.031) were more likely to present with GI symptoms; however age, immunosuppression, and IBD were not associated with GI symptoms at presentation. Only older age was significantly associated with higher rate of liver test abnormalities at presentation (OR 1.01, 95%CI 1.00-1,02, p=0.031).

Both GI manifestations (78% versus 70% for patients without GI symptoms, p=0.007) and liver injury (87% versus 76% for patients without liver injury, p<0.001) on presentation were associated with higher admission rate. Those with GI symptoms had lower rates of death (8.5% versus 16.5% in patients without GI symptoms, p=0.003), and lower risk of the composite of death and ICU admission (28% versus 38% in patients without GI symptoms, p=0.006) in univariable analysis.

In multivariable analysis, liver injury at presentation (OR=2.53, p<0.001), as well as older age (OR 1.03, p<0.001), number of comorbidities (OR=1.19, p=0.021), tachypnea (OR=1.73, p=0.008) and severe hypoxia (OR=1.47, p=0.047) remained independent predictors of the composite outcome of death or ICU admissions in patients admitted with COVID-19, but GI manifestations did not have any significant effect on the outcome (Supplementary table 1 ).

The independent predictors of the composite outcome of death or ICU admission from the multivariable model were then analyzed to find an optimal decision tree for splitting patients into low and high risk categories and predicting the composite outcome (Supplementary figure 1) . The first node of the decision tree was hypoxia as the most informative predictor, followed by presence of liver injury as the second most informative predictor (second node) in patients with severe hypoxia.

This analysis reveals a high prevalence of GI manifestation and liver injury (based on elevated liver enzymes) at presentation in COVID-19. While both GI and hepatic manifestations were associated with increased admission rates, only liver injury at presentation was an independent predictor of ICU admission and death and ICU admission.

Our results indicate that almost one third of patients reported digestive, most commonly diarrhea. One potential explanation for the high rate of diarrhea seen may be related to the SARS-CoV-2 virus's high affinity for angiotensin-converting enzyme 2 receptor, and the abundant ACE2 expression on colonic and ileal epithelial cells 1 . Prior studies, suggest that the presence and severity of digestive symptoms on initial presentation was correlated with worsening disease severity 2 . In contrast, we observed a trend for the presence of GI symptoms on initial presentation to be associated with less severe disease in univariable analysis (Supplementary table 1) , and no significant effect in multivariable analysis. This might be due to higher admission rates in patients with relatively mild respiratory involvement but significant GI symptoms.

In our cohort, 62% presented with at least one elevated liver enzyme, similar to the available literature 3 . We did not find the elevation of either total bilirubin or alkaline phosphatase to be common, and did not observe any cases of clinically significant acute liver injury or acute liver failure as a complication of COVID-19. The presence of liver injury on presentation, however, was associated with a significantly higher risk of ICU admission and death. High prevalence of liver injury in COVID-19 may be due to direct viral infection of liver cells 4 . However, the pathology of hepatic injury in COVID-19 is likely multi-factorial, and may include an indirect reflection of the systemic inflammatory response resulting in compromised vascular hemodynamics and immune hyperactivity and cytokine activation [5] [6] [7] .

In summary, we found that COVID-19 patients commonly exhibit GI manifestations. Liver injury was also commonly seen on initial presentation, and was independently associated with poor clinical outcomes. These results provide clarification of the diagnosis of patients with COVID-19, and can be considered in risk stratification. ^Data are mean (SD), n(%), or n/N (%). Pvalues are calculated using Student t and Chi-squared tests. * Diagnostic delay defined as time between first symptom and performing the first COVID-19 PCR test. VTE: venous thromboembolism; IBD: inflammatory bowel disease; NSAID: non-steroidal anti-inflammatory drug; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; aPTT: activated partial thromboplastin time.

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