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. 2021 Jan;74(1):148-155.
doi: 10.1016/j.jhep.2020.07.040. Epub 2020 Aug 1.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients

Jordi Colmenero  1 , Manuel Rodríguez-Perálvarez  2 , Magdalena Salcedo  3 , Ana Arias-Milla  4 , Alejandro Muñoz-Serrano  4 , Javier Graus  5 , Javier Nuño  6 , Mikel Gastaca  7 , Javier Bustamante-Schneider  7 , Alba Cachero  8 , Laura Lladó  8 , Aránzazu Caballero  3 , Ainhoa Fernández-Yunquera  3 , Carmelo Loinaz  9 , Inmaculada Fernández  9 , Constantino Fondevila  1 , Miquel Navasa  1 , Mercedes Iñarrairaegui  10 , Lluis Castells  11 , Sonia Pascual  12 , Pablo Ramírez  13 , Carmen Vinaixa  14 , María Luisa González-Dieguez  15 , Rocío González-Grande  16 , Loreto Hierro  17 , Flor Nogueras  18 , Alejandra Otero  19 , José María Álamo  20 , Gerardo Blanco-Fernández  21 , Emilio Fábrega  22 , Fernando García-Pajares  23 , José Luis Montero  24 , Santiago Tomé  25 , Gloria De la Rosa  26 , José Antonio Pons  13
Affiliations

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients

Jordi Colmenero et al. J Hepatol. 2021 Jan.

Abstract

Background & aims: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate.

Methods: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression.

Results: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit.

Conclusions: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged.

Lay summary: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

Keywords: COVID-19; Calcineurin inhibitors; Epidemiology; Everolimus; Immunosuppression; Mycophenolate; Pneumonia; SARS-CoV-2; Standardised incidence; Standardised mortality; Tacrolimus; Transplantation.

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Conflict of interest statement

Conflicts of interest JC has received lecture fees from Chiesi, Astellas, and Novartis and is an advisory to Chiesi. MR-P has received lecture fees from Astellas, Novartis, and Intercept Pharma. MS has received lecture fees from Astellas, Novartis, and Chiesi and is an advisory to Jazz and Novartis. MG has received speaker fees from and/or acted as advisor for Astellas, Novartis, Chiesi, Baxter, and Medtronic. MN has received lecture fees from Astellas Pharma. MI has received lecture fees from BMS. CV has received lecture fees from Novartis, Abbie, and Gilead. AC has received lecture fees from Astellas Pharma. GB-F has received lecture fees from Bayer and Astellas. JLM has received lecture fees from Bayer and Gilead. JP has received lecture fees by Astellas, Chiesi, and Gilead. AA-M, AM-S, JG, JN, JB-S, AC, LL, AC, AF-Y, CL, IF, CF, LC, SP, PR, MG-D, RG-G, LH, FN, AO, JA, EF, FG-P, ST and GDR have no conflict of interest to disclose regarding this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Epidemiological curve of COVID-19 in Spain from February 28, 2020 until the registry closure on 7 April 2020. Absolute number of cases are shown for the whole Spanish population and for the liver transplant population.
Fig. 2
Fig. 2
Geographical distribution of COVID-19 among autonomous regions in Spain. Absolute number of cases are shown for the whole Spanish population and for the liver transplant population.
Fig. 3
Fig. 3
Kaplan-Meier curves showing the impact of mycophenolate-containing immunosuppression (upper panel) and increased doses (lower panel) on the development of severe COVID-19. The p values were determined using the log rank test.
Fig. 4
Fig. 4
Proposed algorithm to modify immunosuppression in liver transplant patients with COVID-19 according to the findings of the present study. The recommendations should be adapted to each patient taking into account the interval from liver transplantation and the individualised risk of rejection. CNI, calcineurin inhibitors; mTOR, mammalian target of rapamycin.
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References

    1. Ministerio de Sanidad, Gobierno de España https://www.mscbs.gob.es/en/profesionales/saludPublica/ccayes/alertasAct... Available at.
    1. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–1720. - PMC - PubMed
    1. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71:762–768. - PMC - PubMed
    1. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. - PMC - PubMed
    1. Rodriguez-Peralvarez M., Guerrero-Misas M., Thorburn D., Davidson B.R., Tsochatzis E., Gurusamy K.S. Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis. Cochrane Database Syst Rev. 2017;3:CD011639. - PMC - PubMed