Elevated serum aminotransferase levels at presentation are associated with intensive care unit admission in patients with COVID-19

ABSTRACT

Background: Abnormal serum aminotransferase levels have been observed in up to 60% of patients with coronavirus disease 2019 (COVID-19) Higher serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have been observed in hospitalized patients with severe disease However, the association between enzyme levels at the time of hospital admission and disease outcomes remains incompletely characterized Studies suggest that the mechanism of liver injury is multifactorial and may involve microvascular thrombosis We aimed to assess the prognostic value of abnormal AST and ALT on admission of patients with COVID-19 and their association with d-dimer in a large urban cohort in the U S Methods: Demographic and clinical data of 532 consecutive patient admissions for COVID-19 in two large, urban tertiary referral hospitals in Washington DC from March 13 to May 21, 2020 were analyzed Independent variables were initial AST and ALT values within 24 hours of presentation Primary outcomes were admission to intensive care unit (ICU) and inpatient mortality Presenting AST and ALT were examined as continuous and as dichotomized (≤2x and >2x upper limit of normal (ULN)) variables with outcomes Secondary analyses included general linear regression between AST/ALT and presenting d-dimer levels Statistical analysis was performed using RStudio (version 4 0 0) Results: Of 532 patients, 50 5% were male, 66 5% were Black, with a mean age of 60 3±16 4 years old Time from symptom onset to presentation was 6 (IQR = 3-8) days Chronic liver disease was observed in 20 patients (3 8%) (Table 1) Ninety-two patients (17 2%) expired and 164 (30 9%) required ICU care Abnormal AST and ALT levels were seen in 368 (70 4%) and 199 (38 0%) patients, respectively The mean presenting AST (95 1 vs 56 1 U/L, p= 0 017) and ALT (66 7 vs 43 9 U/L, p=0 008) levels were higher in patients who required ICU care compared to those who did not Patients with AST >2x ULN (>66 U/L) or ALT >2x ULN (>98 U/L) were more likely to require ICU care (OR 2 10, p=0 001 and OR 2 03, p=0 041, respectively) However, difference in mortality was not observed between those groups Lastly, AST was positively associated with presenting d-dimer (p=0 04) but not ALT (p=0 11) Conclusion: Liver function test should be obtained on admission and elevation in AST and/or ALT should be factored into patient risk stratification, especially when AST >66 U/L and/or ALT >98 U/L. Observed correlation between AST (but not ALT) and d-dimer supports the notion that AST level may reflect the ischemic burden of affected organs as a result of microvascular thrombosis, including but not limited to the liver. However, given the low specificity of d-dimer, its elevation may correlate more so with disease severity rather than true presence of microvascular thrombi within the liver (Table Presented).