Query: covid liver transplant

title: COVID 19 in liver transplant recipients
abstract: Coronavirus disease 2019 (COVID 19) an infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS CoV 2) has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS CoV 2 infection and higher morbidity and mortality due to constant contact with health care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss 1) the epidemiology and risk factors for SARS CoV 2 infection in LT recipients; 2) the clinical and laboratory features of COVID 19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and 3) the natural history and prognostic factors in LT recipients hospitalized with COVID 19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID 19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

title: T cell mediated response to SARS CoV 2 in liver transplant recipients with prior COVID 19
abstract: Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2 specific T cell mediated immunity (SARS CoV 2 CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS CoV 2 CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN) g FluoroSpot assay after a median of 103 days from COVID 19 diagnosis. Serum SARS CoV 2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post transplant SARS CoV 2 CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN g producing CD4+ than CD8+ responses (93.5% versus 83.9% Positive spike specific and nucleoprotein specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein specific response was present in 83.3% (25/30) An inverse correlation was observed between the number of spike specific IFN g producing SFUs and time from diagnosis (Spearman's rho: 0.418; p value .024) Two recipients (6.5% failed to mount either T cell mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable but declining over time SARS CoV 2 CMI after a median of 3 months from COVID 19, with no meaningful differences with immunocompetent patients.

title: Successful Management of COVID 19 Infection in 2 Early Post Liver Transplant Recipients
abstract: Coronavirus disease 2019 (COVID 19) has affected all facets of life and continues to cripple nations. COVID 19 has taken the lives of more than 2.1 million people worldwide (23) with a global mortality rate of 2.2% (23) Current COVID 19 treatment options include supportive respiratory care, parenteral corticosteroids, and Remdesivir. Although COVID 19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID 19 infection in patients with organ transplants has not been well described in the literature (9, 13) The treatment of COVID 19 differs, based on the organ(s) transplanted (6) Preliminary data suggested that liver transplant patients with COVID 19 did not have higher mortality rates than untransplanted COVID 19 patients (2) Table 1 depicts a compiled list of current published data on COVID 19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID 19 within their post transplant hospitalization course. This potential differentiation needs to be further explored (14) Here, we report two patients who underwent liver transplantation who acquired COVID 19 during their post transplant recovery period in the hospital. Case Descriptions Two patients who underwent liver transplant and contracted COVID 19 in the early post transplant period. Treated with hydroxychloroquine, methylprednisolone, tocilizumab and convalescent plasma. Description of their hospital course, including treatment and recovery.  The management of post liver transplant patients with COVID 19 infection is complicated. Strict exposure precaution practice following organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID 19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID 19 pneumonia in post liver transplant patients. Future studies and experiences from post transplant patients are warranted to better delineate the clinical features and optimal management of COVID 19 infection in liver transplant recipients.

title: COVID 19 in Liver Transplant Recipients
abstract: Coronavirus disease 2019 (COVID 19) has infected over 93 million people worldwide as of January 14, 2021. Various studies have gathered data on liver transplant patients infected with COVID 19. Here, we discuss the presentation of COVID 19 in immunosuppressed patients with prior liver transplants. We also evaluate patient outcomes after infection.  We searched the PubMed database for all studies focused on liver transplant patients with COVID 19.  We identified eight studies that evaluated COVID 19 infection in liver transplant patients (n=494) Hypertension was the most prevalent comorbidity in our cohort. Calcineurin inhibitors were the most common immunosuppressant medications in the entire cohort. The average time from liver transplant to COVID 19 infection in our cohort was 74.1 months. Fever and cough, at 70% and 62% respectively, were the most common symptoms in our review. In total, 50% of the patients received hydroxychloroquine as treatment for COVID 19. The next most prevalent treatment was azithromycin, given to 30% of patients in our cohort. In total, 80% of the patients were admitted to a hospital and 17% required intensive care unit level care, with 21% having required mechanical ventilation. Overall mortality was 17% in our review.  Given the immunocompromised status of liver transplant patients, more intensive surveillance is necessary for severe cases of COVID 19 infection. As liver transplantations have been restricted during the COVID 19 pandemic, further investigation is warranted for studying the risk of COVID 19 infection in liver transplant patients.

title: 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.

title: Covid 19 in liver transplant recipients: the French SOT COVID registry
abstract: Notwithstanding the ongoing coronavirus disease 2019 (Covid 19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid 19.  COVID 19 was diagnosed in patients who had a positive PCR assay for SARS CoV 2 or in presence of typical lung lesions on imaging or specific SARS CoV 2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid 19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded.  Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children) Hospitalized patients had a median age of 65.2 years (IQR: 58.1 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3% hypertension (61.2% diabetes (50.7% cardiovascular disease (20.9% and respiratory disease (16.4% SARS CoV 2 infection was identified after a median of 92.8 months (IQR: 40.1 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9% 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid 19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30 day mortality rate was 20.0% and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality.  In our large nationwide study, Covid 19 in LT recipients was associated with a high mortality rate.

title: 174: Liver Transplant in an Accidental Acetaminophen Overdose With COVID 19
abstract: Fulminant hepatic failure due to acetaminophen toxicity is one of the most common indications for orthotopic liver transplant (OLT) in the acute setting However, it's unknown whether infection with COVID 19 has any effect on successful OLT We report a rare case of OLT in a COVID 19 patient who presented with acetaminophen overdose  The patient was a 27 year old woman who came to the hospital with one week of abdominal pain along with nausea, vomiting, and diarrhea She reportedly had been taking over 8000 mg Tylenol per day for one week in order to continue working Her acetaminophen level was 42mg/ mL and she was started on N acetylcysteine (NAC) She was tested for COVID 19 per hospital protocol and was positive She denied any recent sick contacts, however, it was eventually determined that the patient cared for her significant other who had COVID 19 about two months prior to her hospitalization The patient's Tylenol levels improved with NAC, but her LFTs significantly increased with AST 14,841 and ALT 11,271 and her coagulation profile worsened with an INR of 4 4 Given her stable respiratory status and elevated LFTs she was deemed to not be a candidate for Remdesivir, per the infectious diseases team recommendations The patient was subsequently transferred to a tertiary medical center for further management With worsening mental status, she was started on continuous veno venous hemodialysis (CVVHD) for hyperammonemia and intubated for airway protection CT brain was concerning for cerebral edema and a bolt was placed for intracranial pressure (ICP) monitoring and management Due to the patient's fulminant liver failure and worsening clinical condition, she was approved for a liver transplant COVID 19 test on the day of transplant and was negative However, it was assumed that she had a positive viral load and was treated as such The patient received COVID 19 convalescent plasma therapy the day after her transplant The patient remained intubated until post op day 5 when her ICPs normalized and she met criteria for extubation The patient's renal function subsequently improved and she was discharged in stable condition  This is thought to be the first liver transplant in a patient who tested positive for COVID 19 and describes its management

title: 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: 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,  Between March 1st and June 27th2020, 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.

title: Convalescent plasma therapy and remdesivir duo successfully salvaged an early liver transplant recipient with severe COVID 19 pneumonia
abstract: The impact and clinical spectrum of COVID 19 infection in liver transplant recipients/solid organ transplants are being unveiled during this recent pandemic. The clinical experience of use of current antiviral drugs and immunomodulators are sparse in solid organ transplantation. We present the clinical course of a 49 year old male recipient who underwent living donor liver transplant for recurrent gastrointestinal bleed and contracted severe COVID 19 pneumonia during the third postoperative week. Herein we report the successful management of severe COVID 19 pneumonia using convalescent plasma therapy and remdesivir. Recipient's clinical deterioration was halted after three consecutive convalescent plasma transfusions with improvement in hypoxia and inflammatory markers (interleukin 6 and C reactive protein) The use of convalescent plasma therapy along with remdesivir may be an ideal combination in the management of severe COVID 19 pneumonia in solid organ transplant recipients.

title: COVID 19 in a liver transplant recipient: Could iatrogenic immunosuppression have prevented severe pneumonia? A case report
abstract: Coronavirus disease (COVID) is a new and highly contagious infectious disease caused by the coronavirus (COVID 19 or severe acute respiratory syndrome coronavirus 2) There is limited data regarding the incidence and management of COVID 19 in immunocompromised patients' post transplantation. In the pre COVID 19 era, these patients were already at an increased risk of developing opportunistic infections. These often manifested with atypical symptoms.  We report another case of uneventful COVID 19 pneumonia in a 58 year old male who was 18 mo' post liver transplantation. He received tacrolimus monotherapy since July 2019. The clinical manifestations included only epigastric pain radiating to the right hypochondrium, nausea and vomiting. He had no fevers, cough, shortness of breath, anosmia or dysgeusia even if the chest computed tomography scan revealed an extension of the multiple patchy ground glass density shadows to the upper lobe of the left lung too. He was hospitalised and received a course of oral chloroquine (200 mg x 3 per day) for a period of 10 d. Interestingly, the COVID 19 infection was uneventful though there were no modifications to his tacrolimus dosing. He was successfully discharged. We performed subsequent follow up via telemedicine.  In light of the current pandemic, it is even more important to identify how the liver recipient's patients present and are managed, especially for immunosuppression treatment.