key: cord-0943173-0jozavps
authors: Ferm, Samson; Fisher, Constantine; Pakala, Tina; Tong, Michelle; Shah, Disha; Schwarzbaum, David; Cooley, Victoria; Hussain, Syed; Kim, Sang Hoon
title: Analysis of Gastrointestinal and Hepatic Manifestations of SARS-CoV-2 Infection in 892 patients in Queens, NY
date: 2020-06-01
journal: Clin Gastroenterol Hepatol
DOI: 10.1016/j.cgh.2020.05.049
sha: 47f16f785b333e4449e3ae8f72c53c01f4e40b50
doc_id: 943173
cord_uid: 0jozavps

nan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID 19). 1, 2 The virus enters cells via the angiotensin converting enzyme 2 (ACE2) receptor which is present in enterocytes in the ileum and colon. 3 Gastrointestinal (GI) manifestations include diarrhea, nausea, vomiting, and abdominal pain, and prevalence of GI symptoms varies greatly with a range between 2 to 57 percent. 4 In addition, abnormal liver chemistries are commonly reported. 4 As a medical center at the forefront of the early epidemic in the U.S., we seek to contribute to the growing body of literature that outlines the gastrointestinal and hepatic manifestations of COVID-19.

We performed a retrospective review of consecutive adult, non-pregnant patients admitted to New York-Presbyterian Queens Hospital in Flushing, NY (NYPQ) for SARS-CoV-2 between March 14, 2020 and April 1, 2020. (Refer to Supplemental Methods) Fisher's exact, chi-square, and Wilcoxon rank sum tests were utilized to compare groups, and p<0.05 was considered statistically significant. This study was approved by the NYPQ Institutional Review Board.

A total of 892 patients were included. Forty percent were female. The median age was 59 years (IQR 47-72). Twenty five percent of patients presented with GI symptoms, the most common of which was diarrhea (19.8%). (Table 1) The median AST on admission was 41 U/L (IQR 30-61), and median peak AST was 55 U/L (IQR 36-97). Forty three percent of patients had normal AST on admission, 40.0% borderline elevation (1-2x ULN), 13.8% mild elevation (2-5x ULN) and 2.8% moderate to severe elevation (>5x ULN). The median ALT on admission was 32 U/L (IQR 19-56) and median peak ALT was 47 U/L (IQR 25-91). Sixty percent of patients had normal ALT on admission, 26.5% borderline elevation (1-2x ULN), 11.5% mild elevation (2-5x ULN) and 1.9% moderate to severe elevation (>5x ULN). Median initial total bilirubin was 0.40 mg/dL (IQR 0.3-0.6) and 4.3% of patients had an abnormal initial total bilirubin (>1.2 mg/dL). The median initial alkaline phosphatase (ALP) was 75 U/L (IQR 60-98) and 11.9% had an abnormal ALP on admission (>130 U/L). Twenty four percent of patients had an abnormal International Normalized Ratio (INR, defined as >1.13) on admission. Abnormal initial total bilirubin was associated with increased mortality (39% vs. 24%; p=0.04), but not ICU admission, rate of intubation, or LOS. An abnormal initial INR was not associated with ICU admission, intubation, LOS or mortality. Patients treated with Hydroxychloroquine, Azithromycin or Tocilizumab were more likely to have abnormal peak ALT and AST levels.

There was no difference between patients with or without GI symptoms on presentation with regard to rate of intubation (p=0.3), ICU admission (p=0.4), length of stay (p=0.8), or mortality (p=0.067). (Supplementary Table 1) An abnormal initial AST as compared to a normal initial AST was associated with higher rates of intubation (18% vs. 12%; p=0.01), ICU admission (18% vs. 11%; p=0.005), and mortality (28% vs.

20%; p=0.009). (Supplementary Table 2 )

Gastrointestinal manifestations are common presenting features of COVID-19, occurring in 25% of our patient population. This finding supports the theory of SARS-CoV-2 gastrointestinal entry and infection via the ACE2 receptor. 3 GI symptoms were not associated with increased rates of ICU admission, intubation, LOS or mortality, suggesting that they do not portend a more severe disease course.

AST was more often elevated compared to ALT, which is distinct from other viral induced liver injury, 5 and may be a useful indicator of SARS-CoV-2 infection. An elevated initial AST was associated with poorer outcomes including higher rates of ICU admission, intubation and mortality. AST is located in the cytosol and the mitochondria, and viral damage to mitochondrial components has been postulated as a mechanism for release of AST. 6 Additionally, greater rise of AST could reflect injury to zone 3 of the hepatocyte which is most susceptible to hypoxia and is the largest hepatic reservoir of AST. 7 Abnormal initial ALT was not associated with poorer outcomes. This may be due to wider parenchymal distribution of AST (including skeletal muscle, cardiac, kidney and lung tissue), which supports multi-organ injury seen in COVID-19. Bilirubin and alkaline phosphatase levels were not considerably elevated.

Limitations of our study include its retrospective design. Collection of data is limited by recall bias of both patients and healthcare professionals involved at time of intake.

We report a large, single-center analysis of the gastrointestinal and hepatic manifestations of COVID-19. Gastrointestinal symptoms and elevation in liver chemistries were common in our patient cohort and may be clinically useful in stratifying the risk of disease severity. 

Follow-up data was extracted until May 1, 2020. Extracted data included patient demographics, comorbidities, clinical symptoms, baseline and peak laboratory values parameters, clinical course (including ICU admission and need for invasive mechanical ventilation) and outcome (discharged, deceased, currently or admitted at time of data collection). Race and ethnicity data were collected by patient self-reporting from a set of predetermined categories. Specific laboratory values collected included initial and peak values of: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP). Liver chemistries were defined as normal, borderline, (<2x Upper Limit of Normal (ULN)), mild (2-5x ULN), moderate (5-15x ULN), severe (>15x ULN) or massive (>10,000). These categories were based on American College of Gastroenterology Clinical Guidelines. 9 Study data were collected and managed using REDCap electronic data capture tools hosted at Weill-Cornell Clinical and Translational Science Center. Descriptive statistics were generated to describe the study population using N (%) and median and Interquartile Range (IQR). Fisher's exact, chi-square, and Wilcoxon rank sum tests were utilized to compare patients with and without GI symptoms and those with abnormal and normal AST and ALT values (initial and peak) on key clinical and demographic characteristics of interest Supplementary Table 2 . Association between abnormal initial and peak AST and ALT and outcomes

Director-General's remarks at the media briefing on 2019-nCoV on 11

A pneumonia outbreak associated with a new coronavirus of probable bat origin

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

Standard liver tests

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

Liver enzyme alteration: a guide for clinicians