key: cord-0698943-ep3hwn9y
authors: Kemme, Sarah; Yoeli, Dor; Sundaram, Shikha S.; Adams, Megan A.; Feldman, Amy G.
title: Decreased access to pediatric liver transplantation during the COVID‐19 pandemic
date: 2021-10-11
journal: Pediatr Transplant
DOI: 10.1111/petr.14162
sha: f0a0dca8d779d72d826b857abdb6b217e5f19a55
doc_id: 698943
cord_uid: ep3hwn9y

BACKGROUND: The COVID‐19 pandemic has affected all aspects of the US healthcare system, including liver transplantation. The objective of this study was to understand national changes to pediatric liver transplantation during COVID‐19. METHODS: Using SRTR data, we compared waitlist additions, removals, and liver transplantations for pre‐COVID‐19 (March‐November 2016–2019), early COVID‐19 (March‐May 2020), and late COVID‐19 (June‐November 2020). RESULTS: Waitlist additions decreased by 25% during early COVID‐19 (41.3/month vs. 55.4/month, p < .001) with black candidates most affected (p = .04). Children spent longer on the waitlist during early COVID‐19 compared to pre‐COVID‐19 (140 vs. 96 days, p < .001). There was a 38% decrease in liver transplantations during early COVID‐19 (IRR 0.62, 95% CI 0.49–0.78), recovering to pre‐pandemic rates during late COVID‐19 (IRR 1.03, NS), and no change in percentage of living and deceased donors. White children had a 30% decrease in overall liver transplantation but no change in living donor liver transplantation (IRR 0.7, 95% CI 0.50–0.95; IRR 0.96, NS), while non‐white children had a 44% decrease in overall liver transplantation (IRR 0.56, 95% CI 0.40–0.77) and 81% decrease in living donor liver transplantation (IRR 0.19, 95% CI 0.02–0.76). CONCLUSIONS: The COVID‐19 pandemic decreased access to pediatric liver transplantation, particularly in its early stage. There were no regional differences in liver transplantation during COVID‐19 despite the increased national sharing of organs. While pediatric liver transplantation has resumed pre‐pandemic levels, ongoing racial disparities must be addressed.

On March 13, 2020, the US declared a state of emergency due to the SARS-CoV-2 virus that causes COVID-19. 1 Since that time, COVID-19 has had a profound impact on every aspect of the US healthcare system, including solid organ transplantation. Although the Centers for Medicare and Medicaid Services classified solid organ transplantation as a Tier 3b procedure that should not be postponed during COVID-19, uncertainty about mechanisms of transmission, availability of hospital resources, intensive care unit beds, supplies, and personal protective equipment as well as the potential risk of COVID-19 for donors, recipients, and staff led many transplant centers across the country to reconsider their transplantation practices. 2 There was also concern regarding the ethics of LDLT during that a healthy donor could be exposed to COVID-19 while in the hospital. [3] [4] [5] A national survey of high-volume adult US LT centers performed in March 2020 revealed that 68% of LDLT programs were completely suspended, and 73% of DDLT programs were under some level of restriction due to A follow-up study using data from the SRTR demonstrated that in the adult LT population, COVID-19 resulted in fewer WL additions, DDLTs, and LDLTs. This study also found significant differences in COVID-19's impact on adult LT at both the state and regional levels, with centers in states with the highest incidence of COVID-19 having 49% more WL deaths and 34% fewer DDLTs. 6 Children with end-stage liver disease, ALF, and unresectable hepatoblastoma are dependent on LT for long-term survival. Many children with end-stage liver disease require urgent transplantation due to complications such as portal hypertension, recurrent cholangitis, and refractory malnutrition. With a shortage of size appropriate grafts, LDLT is a critical option for children on the LT WL. Studies have demonstrated that LDLT has equal if not superior outcomes to DDLT. [7] [8] [9] In 2019, LDLT accounted for 14% of all pediatric LTs and 18% of all LTs for children under the age of six. 10 Racial and ethnic disparities are well described in both pediatric and adult liver transplantation. Specifically, LDLT is less likely to be used for black pediatric liver transplant candidates. 11 Understanding that COVID-19 resulted in center-specific transplant policy changes, with known suspension of many LDLT programs, we sought to utilize SRTR data to quantify changes in national pediatric LT WL additions, WL removals, WL mortality, LDLT, and DDLT between three time periods: pre-COVID-19 (March-November 2016-2019), early COVID-19 (March-May 2020), and late COVID-19 (June-November 2020). We also sought to understand how existing racial and ethnic disparities within pediatric liver transplantation were impacted by COVID-19. cases in the US during the 2020 calendar year, with a relative plateau in between the two. 1 We compared counts during the same monthly periods (March-May, June-November) pre-COVID-19 and during COVID-19. 

Categorical variables were presented as counts and percentage and compared using chi square analyses, with pre-COVID-19 pandemic as the reference time period. Pairwise comparisons were then performed for any categorical variables with overall statistical significance in order to determine, which specific variable(s) contributed to its significance. Continuous variables were presented as mean and SD, and compared using two-sample Student's t test or ANOVA as appropriate. The IR for each WL event per time period was calculated by dividing the total event count by the cumulative person-time contributed by each candidate on the WL during the time period of interest. To evaluate for differential impact of COVID-19 on WL events by race/ethnicity, IR were also stratified as white versus nonwhite candidate/recipient race/ethnicity, with non-white including black, Hispanic, Asian, and other non-white categories as defined in the SRTR/OPTN database. Incidence rates were compared using IRR. An α of 0.05 was used to define statistical significance. Forest plots of IRR were created using GraphPad Prism 9.1.0 (San Diego, CA: www.graph pad.com). All other analyses were performed using 

Characteristics of candidates added to the WL are presented in Table 1 . Overall, WL additions were 25% fewer during early COVID-19 compared to pre-COVID-19 (41.3/month vs 55.4/ month, p = .004). Candidates ages 1-10 years were less likely to be added to the WL during early and late COVID-19 (23% and 19%, respectively, compared to 28% pre-COVID-19, p = .004) compared to pre-COVID. There were significant differences in WL additions based on race, with proportion of black candidates added to the WL dropping significantly in early COVID-19 (11%) compared to pre-COVID-19 (16%), and rebounding in late COVID-19 (21%) (p = .04). Underlying diagnosis, listing PELD and MELD scores, gender, and insurance type were similar in early and late COVID-19 as compared to pre-COVID-19. There were no significant differences across the different time periods in WL additions based on OPTN region (Table S1 ). There were no differences in overall proportion of WL dropouts from death or worsened condition during pre-COVID-19, early COVID-19, or late COVID-19 periods (5% vs. 6% vs. 5%, p = .5). There were no differences in underlying diagnosis, PELD/MELD, gender, age, weight, or race for those who did dropout from the WL. (Table S2 ).

There was a 38% decrease in the rate of pediatric LT in early COVID-19 as compared to pre-COVID- 19 and 54% in early and late COVID-19 (p < .001); subsequently, the proportion of local and regional sharing decreased. There were no significant differences across the different time periods in distribution of LT based on OPTN region (Table S3) . In summary, we found that the COVID-19 pandemic, particularly early on, decreased access to pediatric LT. Though not to the degree of the adult LT population, WL additions and incidence rate of transplantation decreased significantly. While differences in impact were not observed on the regional level, there were significant racial differences. Future studies are needed to evaluate the outcomes for both living donors and LT recipients during COVID-19 to understand if they were at higher risk for infectious complications or poor outcome. This information will be critical in informing future recommendations for pediatric LT centers. 

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Dr. Kemme wrote the first draft of the manuscript and did not receive any honorariums, grants, or forms of payment to produce the manuscript. All authors listed on the manuscript meet the ICMJE definition of authorship and have approved the manuscript being submitted.

The raw data that support the findings of this study are available 

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