COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis

Abstract

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.

Keywords: COVID-19; SARS-CoV-2; liver transplantation.

FIGURE 1

Search strategy and study selection used in this systematic review as per PRISMA protocol

FIGURE 2

Quality assessment of included studies. (green—low risk of bias; yellow—unclear risk of bias; red—high risk of bias)

FIGURE 3

A, Pooled prevalence of intensive care admission in liver transplant recipients diagnosed with COVID‐19. The red dashed line represents the overall effect size of the studies (0.22) and prevalence of 22%. The edges of the blue diamond represent 95% confidence intervals (0.12‐0.32). ES = Effect size. B, Pooled prevalence of acute respiratory distress syndrome in liver transplant recipients diagnosed with COVID‐19. The red dotted line represents the overall effect size of the studies (0.56) and prevalence of 56%. The edges of the blue diamond represent 95% confidence intervals (0.26‐0.86). ES = Effect size; C, Pooled prevalence of mechanical ventilation requirement in liver transplant recipients diagnosed with COVID‐19. The red dashed line represents the overall effect size of the studies (0.24) and prevalence of 24%. The edges of the blue diamond represent 95% confidence intervals (0.12‐0.36). ES = Effect size. D, Pooled prevalence of hospital mortality in liver transplant recipients diagnosed with COVID‐19. The red dotted line represents the overall effect size of the studies (0.20) and prevalence of 20%. The edges of the blue diamond represent 95% confidence intervals (0.13‐0.28). ES = Effect size. E, Pooled prevalence of intensive care mortality in liver transplant recipients diagnosed with COVID‐19. The red dashed line represents the overall effect size of the studies (0.41) and prevalence of 41%. The edges of the blue diamond represent 95% confidence intervals (0.19‐0.63). ES = Effect size

FIGURE 4

A, Forest plot representing odds ratio (OR) of COVID‐19 related death in liver transplant recipients in age group ≥ 60‐65 years vs <60‐65 years while comparing the weight of the studies in the meta‐analysis. The diamond shows higher risk ≥ 60‐65 year old group following analysis (red dashed line represents OR of 4.26). The edges of the blue diamond represent 95% confidence intervals (2.14‐8.49). B, Forest plot representing odds ratio (OR) of COVID‐19 related death in liver transplant recipients in late post‐transplant period group (>2 years) in contrast to early post‐transplant period (≤2 years) while comparing the weight of the studies in the meta‐analysis. The diamond shows the odds ratio in late post‐transplant group 3.07 and is represented by the red dotted line. The edges of the blue diamond represent 95% confidence intervals (0.65‐14.46). C, Forest plot representing the proportion of COVID‐19 related death in liver transplant recipients in the female population in contrast to the male population while comparing the weight of the studies in the meta‐analysis. The diamond shows no increased risk between the groups; odds ratio 1.05 is represented by the red dashed line, and the edges of the blue diamond represent 95% confidence intervals (0.62‐1.80)