Characteristics of Liver transplant patients infected with COVID-19.

Dear Editors:

With great interest, we have read this multicenter research network study from Mansoor and colleagues entitled “Clinical Characteristics, Hospitalization and Mortality Rates of COVID-19 Among Liver Transplant Patients in the United States.”The study had described the characteristics of liver transplant (LT) patients infected with coronavirus disease 2019 (COVID-19) and the rates of hospitalization, mortality, thrombosis, and intensive care unit (ICU) requirements. Within their study, fever (10%) was the most common presenting symptom, followed by cough (8%), malaise and fatigue (8%), dyspnea (10%), and gastrointestinal symptoms (8%). The incidence of hospitalization, ICU care admission, and mortality among LT patients were 40%, 8%, and 8%, respectively, and these outcomes were significantly higher than in the non-LT cohort. The study was designed retrospectively with incomplete documentation and recall bias. The sample size was not large enough to support the results with high confidence. Moreover, the presenting symptoms, hospitalization, ICU care, and mortality among LT patients were lower than reported by the other 2 multicenter studies from Spain and Europe. ,

We have performed a single-arm meta-analysis from data of three multicenter studies including the present study using OpenMeta[Analyst] software (Center for Evidence-Based Medicine at Brown University in Providence, Rhode Island). A total of 294 LT patients with COVID-19 infection were included from 3 multicenter studies from Europe, Spain, and the United States (present study).1, 2, 3 The estimated mean age of the patients from 3 studies was 62.72 years (95% confidence interval [CI], 59.09–66.36).

The results of our single-arm meta-analysis also showed that the order of presenting symptoms was similar to this study. However, the proportion of patients presenting with those symptoms were significantly higher than reported by Mansoor et al (Supplementary Figure 1). Our analysis showed that the proportion of patients presenting with fever was 53.7% (95% CI, 4.2–103.2). The proportion of patients presenting with cough was 44% (95% CI, 0.6–88.7). The proportion of patients presenting with hypoxemia or dyspnea was 31.3% (95% CI, 4.3–58.2). The proportion of patients presenting with fatigue and malaise was 31.7% (95% CI, –15.6 to 78.9). Finally, the proportion of patients presenting with symptoms requiring ICU care was 24.2% (95% CI, 4.7–43.7). Our study showed that 66.1% (95% CI, 35.8–96.3) were hospitalized, which was higher than the present study. Patients who required ICU care and the died were 8.6% (95% CI, 5.4–11.8) and 12.3% (95% CI, 6.0–18.6), respectively, which were not significantly higher than the present study.

Supplementary Figure 1

Forest plot showing results of single-arm analysis. (A) Age. (B) Fever. (C) Cough. (D) Malaise and fatigue. (E) Gastrointestinal symptoms. (F) Hospitalization. (G) ICU care. (H) Mortality.

Moreover, this study had not analyzed the risk factor of severe COVID among hospitalized patients with LT. An earlier study by Colmenero et al had shown that the Charlson comorbidity index (relative risk [RR], 1.28; 95% CI, 1.05–1.56), male sex (RR, 2.49; 95% CI, 1.14–5.41), dyspnea at diagnosis (RR, 7.25; 95% CI, 2.95–17.82), and baseline immunosuppression containing mycophenolate (RR, 3.94; 95% CI, 1.59–9.74) were independent predictors of severe disease during multivariate analysis. Differentiating the predictors of severe disease between LT and non-LT COVID patients will certainly guide physicians for more evidence-based appropriate care. Moreover, a previous international registry study had shown that age (odds ratio, 1.06 [95% CI, 1.01–1.11] per 1-year increase), serum creatinine concentration (1.57 [95% CI, 1.05–2.36] per 1 mg/dL increase), and non-liver cancer (18.30 [95% CI, 1.96–170.75]) were associated with death among LT recipients. The study by Mansoor et al has compared the associated comorbid conditions between 2 groups, but had not performed an analysis to identify the risk factors associated with death among LT patients.

In conclusion, patients with LT have worse clinical outcomes of COVID-19 than those without LT. Further studies regarding the comprehensive management of patients with LT and COVID-19 are urgently needed to provide better health care to this patient population.