OUTCOMES FROM SARS-COV-2 INFECTION IN LIVER TRANSPLANT RECIPIENTS: A CASE SERIES

Background and Aim Coronavirus disease 2019 (COVID-19), or SARS CoV-2, poses a unique challenge in immunosuppressed cohorts. International data regarding the impact of liver transplantation (LT) on outcomes of COVID-19 infection remains conflicting, with emerging evidence suggesting that age and comorbidities confer a greater risk of mortality than LT alone. Use of mycophenolate mofetil (MMF) as an immnosuppressant (IS) has been identified as an independent predictor of severe disease and current guidelines recommend consideration of IS reduction based on severity of COVID-19 infection.1 In Australia, we have been fortunate to be largely spared significant outbreaks of COVID-19 and therefore our experience in managing COVID-19 in LT recipients is limited. This case series describes outcomes of COVID-19 in a liver transplant cohort managed at a large tertiary centre. Methods Liver transplant recipients known to the Victorian Liver Transplant Unit with confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab were included. Data was obtained retrospectively from electronic medical records. Severe SARS-CoV-2 pneumonia was defined as warranting ICU admission, vasopressor support, or intubation. Results Four LT recipients (median age 54 years, all male) were identified from our registry as testing positive for COVID-19 (Table 1). The median interval from transplantation to infection was 10.5 years (range: 6-17 years). All patients were receiving calcineurin inhibitors as immunosuppression at the time of diagnosis. Two patients were on combination therapy with mycophenolate mofetil (MMF), one of whom also received low-dose prednisolone. Two patients required hospital admission for management of symptomatic disease. Age was an independent risk factor for hospital admission (p=0.02). Supplemental oxygen and dexamethasone therapy were used in one of the hospitalised patients. No patients met criteria for severe COVID-19 pneumonia. Patients receiving MMF had this withheld for a mean of 16.5 days. All patients survived with no episodes of acute cellular rejection or graft loss. Conclusion This single centre experience managing COVID-19 in liver transplant recipients showed good clinical outcomes. Increasing age was associated with a higher incidence of hospital admission consistent with large European cohort studies.2 Two patients who had their MMF withheld did not experience acute cellular rejection or graft loss, which could provide some reassurance to clinicians managing similar situations in the future.

Clinical Presentation, Treatment, and Mortality Rate in Liver Transplant Recipients With Coronavirus Disease 2019: A Systematic Review and Quantitative Analysis.

Liver transplant recipients may be at increased risk for adverse outcomes with coronavirus disease 2019 (COVID-19) infection because of chronic immunosuppression and associated comorbidities. There is a paucity of literature describing clinical presentation, treatments, and outcomes in liver transplant recipients with COVID-19. A systematic search was performed for articles published up to June 15, 2020, revealing 223 liver transplant recipients with COVID-19 in 15 studies. Patients most commonly presented with fever (66.7%), dyspnea (34.0%), and diarrhea (28.4%). Of these, 77.7% required hospitalization, 24% had mild disease, 40% had moderate disease, and 36% had severe disease. Immunosuppression was modified in 32.8% of recipients. The case fatality rate was 19.3%. Dyspnea on presentation, diabetes mellitus, and age 60 years or older were significantly associated with increased mortality (P ≤ .01) with a trend to higher mortality rate observed in those with hypertension and those receiving corticosteroids at the time of COVID-19 diagnosis. The median time from symptoms to death was 11.5 days (2-45 days). In conclusion, liver transplant recipients with severe acute respiratory syndrome coronavirus 2 are overrepresented with regard to severe disease and hospitalizations. Older liver transplant patients with diabetes mellitus or hypertension, who are on maintenance corticosteroids, with a diagnosis of COVID-19 and describing breathlessness should be aggressively monitored for signs of deterioration because of the risk for mortality.