Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study

Abstract

Background and aims Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking Methods Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis, Results Between March 1st and June 27 th 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39/204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age > 70 (HR 4.16; 95%CI 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR 0.55; 95%CI 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR 1.95; 95%CI 1.06 - 3.58) and chronic kidney disease (HR 1.97; 95%CI 1.05 - 3.67) emerged as associated with death Conclusions Twenty-five per cent of patients requiring hospitalization for Covid-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

COVID-19 in Immunosuppressed Children

“…This scarce susceptibility replicates that of the general pediatric population and denies a role of immunosuppression as an additional risk in transplanted children. Even data from the European Liver Transplant Registry demonstrate a protective effect of the tacrolimus on the development of severe disease in adults ( 102 ).…”

Uremia-Associated Immunological Aging and Severity of COVID-19 Infection

“…In the case of severe COVID-19 infection, controlling the inflammatory response by high dose steroid is currently the best option (103). A recent study among recipients of a liver transplant with COVID-19 infection showed that the use of tacrolimus was associated with a significant reduction of mortality (104). This findings underlines that limiting the excessive T cell response, in this case by tacrolimus, is a key element in harnessing the morbidity and mortality of COVID-19.…”

Impact of COVID-19 on the outcomes of gastrointestinal surgery

“…376 (78%) patients required hospitalization, including 147 (39%) patients requiring ICU care and 77 (20.5%) patients who died within 1 month after the diagnosis of COVID-19 (Table 3) [52]. [6,16,20,65,67,69,70] Intraoperative considerations in suspected or confirmed COVID-19 patient [6,16,19,20] Postoperative considerations in suspected or confirmed COVID-19 patient [6,19,20,69,70] Screening with COVID-19 symptom evaluation and body temperature measurement Use of regional anesthesia The multicenter study from the European LT Registry (ELTR) is the largest study reporting the outcomes of SAR-CoV-2 infection in 243 adult symptomatic LT patients from 36 centers [53]. They found that 84% of patients required hospitalization, including ICU admission in 19% of cases.…”

“…About 20% of LT patients died due to COVID-9, with respiratory failure being the primary cause of death. On multivariate analysis, the authors found that age > 70 years, comorbidities such as diabetes mellitus, and chronic kidney disease were independent risk factors for mortality (Table 3) [53].…”

“…In the ELTR study, the authors reported the use of hydroxychloroquine, lopinavir-ritonavir, low molecular weight heparin, high doses of corticosteroids, and tocilizumab for the SARS-CoV-2 infection in LT recipients [53]. Surprisingly, the use of tacrolimus was associated with a significantly reduced risk of mortality in LT recipients with COVID-19 infection [53]. On subgroup analysis, the authors found that patients receiving tacrolimus were younger, had fewer comorbidities, and were less frequently treated with ACE or ARB inhibitors.…”