An increase in aspartate aminotransferase levels can predict worsening disease severity in Japanese patients with COVID-19

Background: The prognostic significance of liver dysfunction in coronavirus disease 2019 (COVID-19) patients remains unclear. This study aimed to investigate the association between liver function test results and severe disease progression in COVID-19 patients. Methods: We conducted a retrospective study that included consecutive Japanese COVID-19 patients between February 2020 and May 2021. We identified the predictive variables for severe disease progression by utilizing established factors and multivariate logistic analysis. The Kaplan-Meier method was used to estimate severe disease-free survival. Furthermore, we evaluated the hazard ratios (HRs) among three aspartate aminotransferase (AST) grades using Cox regression analysis: grade 1, AST < 30 U/L; grade 2, 30 U/L< AST < 60 U/L; and grade 3, AST >60 U/L. Results: After exclusion, 604 symptomatic COVID-19 patients were enrolled during the study period, and 141 (23.3%) of them developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis of the fourteen significant variables revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were significant predictive variables. Severe disease-free survival times were significantly separated according to AST grade severity (HR: grade 2 to grade 1: 4.07 (95% CI: 2.06-8.03); HR: grade 3 to grade 1: 7.66 (95% CI: 3.89-15.1)). Conclusion: AST levels at admission were an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial 2021-10-3 ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted in accordance with the Declaration of Helsinki, and the institutional review board of Toyonaka Municipal Hospital approved this study (2021-10-3). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available on request from the corresponding author Kengo Matsumoto. The data are not publicly available due to restrictions (e.g., they contain information that could compromise the privacy of the research participants).