Outcomes of SARS-CoV-2 Infection in Patients with Chronic Liver Disease and Cirrhosis: a N3C Study

Ge, Jin; Pletcher, Mark J.; Lai, Jennifer C.; Harper, Jeremy R.; Chute, Christopher G.; Haendel, Melissa A.

Background and Aims In chronic liver disease (CLD) patients with or without cirrhosis, existing studies on the outcomes with SARS-CoV-2 infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record (EHR) dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis. Methods We identified all CLD patients with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of 7/1/2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality. Results We isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) Non-Cirrhosis/Negative, 29,446 (13%) Non-Cirrhosis/Positive, 53,476 (24%) Cirrhosis/Negative, and 8,941 (4%) Cirrhosis/Positive patients. Thirty-day all-cause mortality rates were 3.9% in Cirrhosis/Negative and 8.9% in Cirrhosis/Positive patients. Compared to Cirrhosis/Negative, Cirrhosis/Positive had 2.38-times adjusted hazard of death at 30 days. Compared to Non-Cirrhosis/Positive, Cirrhosis/Positive had 3.31-times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (diabetes, heart failure, and pulmonary disease); SARS-CoV-2 infection was associated with increased adjusted hazards of death. Conclusions In this study of ∼221,000 nationally-representative, diverse, and gender-balanced CLD patients; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 was associated with 3.31-times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regarding immune responses to vaccines in patients with severe liver disease.