Jaundice in patients with COVID-19

Background: Hyperbilirubinemia and jaundice secondary to hepatic dysfunction is one of the many extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). We aimed to study the clinical consequences and etiologies of jaundice in patients hospitalized with COVID-19 at a tertiary care medical center during the height of the pandemic in New York City. Methods: We retrospectively analyzed laboratory abnormalities, clinical features, rates of survival and ICU admission, and patterns of liver injury in 551 patients hospitalized with COVID-19 between March 1, 2020 and May 31, 2020. Hepatic jaundice was defined as a serum total bilirubin concentration > 2.5 mg/dL and a direct bilirubin concentration > 0.3 mg/dL. The type of liver injury in patients with jaundice and an elevated alanine aminotransferase (ALT) or alkaline phosphatase (ALP) was characterized as cholestatic, mixed, or hepatocellular at the time of peak total bilirubin by calculating the R factor, computed as serum ALT/upper limit of normal divided by serum ALP/upper limit of normal. Results: Jaundice was present in 49 (8.9%) of patients in the cohort and was associated with significantly worse clinical outcomes (Figure). The mortality rate among jaundiced patients was significantly higher than that in patients without evidence of jaundice (40.8%, vs 18.9%, ∗∗∗p < 0.001). Additionally, patients with jaundice were admitted to the intensive care unit (ICU) more frequently than those without jaundice (69.4% vs 26.9%, ∗∗∗p < 0.001). Jaundiced patients had an increased frequency of fever, leukopenia, leukocytosis, thrombocytopenia, hypotension, hypoxemia, positive blood cultures, elevated serum creatinine concentration, elevated serum procalcitonin concentration, and sepsis. Nine jaundiced patients had an isolated hyperbilirubinemia without abnormally elevated serum ALT or ALP activities. Of the 40 patients with abnormally elevated ALT or ALP activities, 62.5% had a cholestatic pattern of liver injury, 20.0% mixed, and 17.5% a hepatocellular pattern. Conclusion: Jaundice in patients with COVID-19 is an ominous sign, with an increased rate of ICU admission and a mortality rate similar to that for patients receiving invasive mechanical ventilation. The main etiologies of liver dysfunction leading to jaundice appear to be sepsis, a severe systemic inflammatory response, and hypoxic/ischemic hepatitis.