Results Demographics and general characteristics of study population Among 19 centres from seven European countries involved in the study, 12 registered at least one case. Of the 11 790 liver transplant recipient in regular follow-up overall, 91 patients were reported, of whom 57 were classified as confirmed cases and considered for statistical analysis (figure 1). Overall, 40 recipients (70%) were male and median age (IQR) at diagnosis was 65 (57–70) years. Mean body mass index (BMI, kg/m2) was 26.0±4.6, with 23 (43%) and 8 (14%) patients being overweight and obese, respectively. Eleven (19%) and 21 (37%) subjects were defined as very short-term and very long-term transplant recipients, respectively. Additionally, median time (IQR) from transplant to COVID-19 diagnosis was 6 (2–13) years, and 32 (56%) patients had been transplanted more than 5 years before COVID-19 diagnosis. Characteristics related to indication for liver transplantation and underlying liver disease are summarised in table 1. With regard to comorbidities, 21 (37%) and 10 (18%) patients had one and more than one cardiovascular (CV) disease, respectively. In terms of CV risk factors, 32 (56%) recipients had arterial hypertension, and 21 (37%) diabetes mellitus, while 7 (12%) were active or former smokers. Sixteen (28%) patients had chronic kidney disease. Furthermore, 24 (42%) subjects had a clinical history of neoplasia (20 with hepatocellular carcinoma (HCC)), which was active in 5 (9%) patients. Concomitant respiratory diseases were found in 13 (23%) patients. Only one patient was HIV positive. Concerning pharmacological therapy for CV prevention, 13 (23%) recipients were on ACE inhibitors or sartans, while 9 (16%) were on low-dose aspirin. Figure 1 Flowchart of the study design. Table 1 Demographic characteristics of liver transplant recipient with SARS-CoV-2 infection Study population Results Patients, n 57 Sex, male, n (%) 40 (70) Ethnicity, Caucasian, n (%) 53 (93) Age, years, median (IQR) 65 (57–70)  Age ≥65, n (%) 29 (51)  Age <65, n (%) 28 (49) BMI, kg/m2, mean (SD) 26.0±4.6 BMI, classes, n (%)    18–24.9 23 (43)  25–29.9 23 (43)  >30 8 (14) Time from transplant to diagnosis, years, median (IQR) 6 (2–13)  Very long-term transplant recipients, n (%)  21 (37)  Very short-term transplant recipients, n (%) 11 (19)  Long-term transplant recipients, n (%) 32 (56) Indication to LT, n (%)    End-stage liver disease 38 (68)  Liver tumour 16 (29)  Acute liver failure 4 (7)  Other 9 (16) Underlying liver disease, n (%)    ALD 15 (26)  Viral 24 (42)   HCV 11 (19)   HBV 13 (23)  PSC 3 (5)  PBC 4 (7)  NAFLD/NASH 2 (4)  Autoimmune 1 (2)  Hemochromatosis 1 (2)  Wilson’s disease 1 (2)  Other 10 (18) HCC, yes, n (%) 20 (35) Comorbidities, n (%)    Cardiovascular disease 21 (37)   Coronary artery disease 7 (12)   Heart failure 9 (16)   Atrial fibrillation 6 (11)   Stroke 1 (2)   Other 8 (14)   >1 cardiovascular disease 10 (18)  Arterial hypertension 32 (56)  Diabetes mellitus 21 (37)  Active cancer 5 (9)  Kidney insufficiency 16 (28)  Respiratory disease 13 (23)   COPD 7 (12)   HIV 1 (2) Smoke history, yes, n (%) 7 (12) Symptoms at presentation, n (%)    Fever 44 (79)  Cough 31 (55)  Dyspnoea 26 (46)  Fatigue and myalgia 32 (56)  GI symptoms 18 (33)   Diarrhoea 16 (28)   Abdominal pain 1 (2)   Vomiting 1 (2)  Anosmia or dysgeusia 4 (7)  Other 8 (14) Concomitant bacterial infection, n (%) 9 (16)  Suspected 3 (6)  Confirmed 6 (11) ALD, alcoholic liver disease; BMI, body mass index; COPD, chronic obstructive pulmonary disease; HCC, hepatocellular carcinoma; LT, liver transplantation; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis. When we considered very-long term recipients in terms of comorbidities, CV disease (57% vs 25%, respectively; p=0.023) and arterial hypertension (76% vs 44%; p=0.028) were significantly more frequent. Presentation of COVID-19 in liver transplant patients At the time of diagnosis, the most commonly self-reported symptoms were fever (44 patients, 79%), cough (31 patients, 55%), dyspnoea (26 patients, 46%), fatigue or myalgia (32 patients, 56%), anosmia or dysgeusia (4 patients, 7%), as well as GI symptoms (18 patients, 33%). Patients who experienced the latter often had more than one GI symptom, diarrhoea being the most frequently reported (16 patients). Other unspecific symptoms included loss of appetite (four patients), headache (one patients) and sore throat (one patient), while confusion and delirium were reported in two hospitalised patients. When long-term and short-term recipients were compared in terms of symptoms at presentation, fever (91% vs 63%, respectively; p=0.019) and dyspnoea (59% vs 29%; p=0.032) were significantly more frequent among long-term recipients. When very short-term recipients were considered, fever (50% vs 85%, respectively; p=0.045) and cough (27% vs 62%, p=0.048) were significantly less prevalent (table 2). Table 2 Differential distribution of symptoms between long-term and short-term liver transplant patients Symptoms,n (%) Overall Long-term transplant recipient P value Very-short term transplant recipient P value No Yes Yes No Sex, male 40 (70) 19 (48) 21 (53) 0.561 10 (25%) 30 (75%) 0.146 Age, years, median (IQR) 65 (57–70) 59 (53–65) 68 (61–76) <0.001 55 (52–70) 65 (59–72) 0.058 BMI, kg/m2, mean (SD) 26.0±4.6 26.1±4.6 25.7±5.1 0.563 26.8±5.7 25.3±3.6 0.043 Fever 44 (79) 15 (63) 29 (91) 0.005 6 (55) 38 (84) 0.045 Cough 31 (55) 11 (46) 20 (63) 0.280 3 (27) 28 (62) 0.048 Dyspnoea 26 (46) 7 (29) 19 (59) 0.032 3 (27) 23 (51) 0.192 Fatigue 32 (56) 11 (44) 21 (66) 0.117 4 (36) 28 (61) 0.184 Conjunctivitis 0 – – – – – – Anosmia/dysgeusia 4 (7) 0 4 (13) 0.131 0 4 (9) 0.573 GI 18 (33) 6 (25) 12 (38) 0.394 1 (9) 17 (38) 0.084 Other 8 (14) 3 (13) 5 (16) 1.000 1 (9) 7 (16) 1.000 In the entire population, the diagnosis of SARS-CoV-2 infection was confirmed by NAAT positivity in nasopharyngeal swab, while one additional patients received BAL. Concerning radiological findings, CT scan and pulmonary radiography showed typical features of the disease in 24 (43%) and 23 (40%) cases, respectively. The main laboratory findings are summarised in table 3. Four patients (8%) displayed relevant increase in liver enzymes (AST and/or ALT>2 × ULN). Conversely, median (IQR) leucocytes, lymphocytes and thrombocytes were 4.5 (3.3–6.0)×1000/µL, 0.79 (0.40–1.10)×1000/µL and 160 (91–268)×1000/μL, respectively. Table 3 Initial laboratory data of liver transplant recipient with SARS-CoV-2 infection Patients tested, n (%) Results Patients with value, n Deviation from reference (%) Blood counts, median (IQR)  Leucocytes (×1000/μL) 51 (90) 4.50 (3.33–6.00) 17 (33)*  Platelets (×1000/μL) 49 (86) 160 (91–268) 17 (35)*  Lymphocytes (×1000/μL) 49 (86) 0.79 (0.40–1.10) 37 (76)* Biochemical and liver-related test, median (IQR)  AST (U/L) 49 (86) 38 (25–53) 13 (26)†  ALT (U/L) 49 (86) 30 (20–42) 10 (20)†  GGT (U/L) 45 (79) 66 (39–161) 29 (64)†  ALP (U/L) 37 (65) 97 (74–171) 9 (24)†  Total bilirubin (mg/dL) 43 (75) 0.70 (0.48–1.09) 10 (23)†  INR (ratio) 42 (74) 1.10 (1.03–1.28) 14 (33)†  Albumin (g/L) 19 (33) 32 (29.5–36.5) 8 (42)*  Creatinine (mg/dL) 50 (88) 1.16 (0.93–1.55) 20 (40)†  Glucose (mg/dL) 36 (63.2) 127.5 (92.5–163.0) 24 (67)† Inflammatory-related markers, median (IQR)  D-Dimer (ng/mL) 17 (29.8) 871 (380–1739) 10 (59)†  LDH (U/L) 31 (54.4) 273 (192–384) 20 (65)†  IL-6 (pg/L) 9 (15.8) 93 (59–288) –  Ferritin (ng/mL) 13 (22.8) 567 (171–1194) 9 (69)† *Below reference. †Above reference. ALP, alanine alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase; IL-6, interleukin-6; INR, international normalised ratio; LDH, lactate dehydrogenase. Concomitant bacterial infection was described in nine patients (16%). Three (6%) of them were defined suspected, since no confirmatory positive cultures were available, although clinical and laboratory findings were suggestive (symptomatic urinary infection, cholangitis and pulmonary coinfection) and six (11%) cases were defined as confirmed (positive blood culture). Gram-positive concomitant infection was found in three patients, while one patient resulted to be infected by Gram-negative strains and two subjects by both Gram-positive and Gram-negative strains. The most common Gram-negative strains belonged to Enterobacteriaceae (two Escherichia coli, one Enterobacter cloacae), whereas between Gram-positive strains enterococci were the most reported. Management of immunosuppression therapy and COVID-19 therapy Baseline immunosuppression therapy and its management are described in table 4. Overall, reduction was observed in 22 (39%) patients, and complete discontinuation was reported in 4 cases (7%). Considering individual therapies, antimetabolites were the most frequently discontinued drugs (18%), whereas calcineurin inhibitors (CNIs) were the most frequently reduced ones (16%). Table 4 Baseline immunosuppression characteristics and modification during the infection Baseline immunosuppression therapy Overall, n (%) No modification, n (%) Reduction, n (%) Discontinuation, n (%) Single agent CNIs 16 (28) 12 (75) 2 (12.5) 2 (12.5)  Cyclosporine 3 (5) 2 (67) 0 1 (33)  Tacrolimus 13 (29) 10 (77) 2 (15) 1 (8) mTORi 2 (4) 1 (50) 0 1 (50)  Everolimus 1 (2) 1 (100) 0 0  Sirolimus 1 (2) 0 0 1 (100) MMF 2 (3) 0 0 1 (100) Steroid 1 (2) 1 (100) 0 0 Two or more agents CNIs+MMF 21 (37) 7 (33) 6 (29) 8 (38)  CNIs – – 5 1  MMF – – 1 7 CNIs+mTORi 3 (5) 1 (33.3) 1 (33.3) 1 (33.3)  CNIs – – 1 0  mTORi – – 0 1 CNIs+steroids 9 (16) 1 (11.2) 4 (44.4) 4 (44.4)  CNIs – – 4 4  Steroids – – 0 0 CNIs+AZA 1 (2) 1 (100) 0 0 mTORi +MMF 2 (3) 1 (50) 0 1 (50)  mTOR – – 0 1  MMF – – 0 0 AZA, azathioprine; CNIs, calcineurin inihibitors, including cyclosporine and tacrolimus; MMF, mycophenolate mofetil; mTORi, mammalian target of rapamycin inhibitor, including sirolimus and everolimus. Concerning specific therapy for COVID-19, 19 (35%) patients received steroids, 22 (44%) hydroxychloroquine and 5 (9%) antivirals, including lopinavir/ritonavir (3 patients), darunavir/cobicistat and remdesivir. Only one patient was treated with tocilizumab, while two more patients were on immunomodulatory therapies because of concomitant comorbities (one on rituximab for active lymphoma and the other one on ruxolitinib for a graft vs host disease). Overall, 35 (63%) and 16 (29%) subjects received at least one and more than one antibiotic drug, respectively. Of those, 15 (27%) were treated with azithromycin as part of the standard care of COVID-19 therapy in some centres.24 As for respiratory support, oxygen therapy was required in more than half of the patients (30, 54%). Of those, the majority required only oxygen therapy through nasal cannula (18 patients, 32%), whereas 8 (14%) subjects received high-flow oxygen. Four (7%) patients required intubation and invasive mechanical ventilation (table 5). Table 5 Therapeutic strategies for COVID-19 and outcomes Study population Results Patients, n 57 Medications, n (%) Steroids (for COVID-19) 19 (35) Antibiotics 35 (63)  Azitromycin 15 (27)  >1 antibiotic 16 (29) Antivirals 5 (9)  Lopinavir/ritonavir 3 (5)  Darunavir/cobicistat 1 (2)  Remdesivir 1 (2) Immunomodulator 3 (5)  Tocilizumab 1 (2)  Rituximab 1 (2)  Ruxolitinib 1 (2) Hydroxychloroquine 24 (44) Oxygen therapy (higher intensity), n (%) Overall 30 (54)  Nasal cannula 18 (32)  Non-invasive ventilation 8 (14)  Invasive mechanical ventilation 4 (7) Outcomes, n (%) Death 7 (12) ARDS 11 (19) ICU admission 4 (7) Hospitalisation (no ICU) 37 (65)  Need for rehabilitation 7 (17) Duration of hospitalisation, median (IQR) Hospital stay 10 (7–22)  ICU stay 16 (10–19) Rehab stay 14 (11–15) ARDS, acute respiratory distress syndrome; ICU, intensive care unit. Clinical outcome in liver transplant patients with COVID-19 Overall, 16 (28%, 95% CI 17% to 42%) patients received outpatient care for COVID-19, while 41 (72%, 95% CI 59% to 83%) subjects were hospitalised, with a median (IQR) hospital stay duration of 10 days (7–22). Among hospitalised recipients, 4 (10%, 95% CI 3% to 23%) were admitted to the ICU and required invasive mechanical ventilation, while 11 (19%, 95% CI 10% to 32%) developed ARDS. Death was registered in seven cases (12%, median time from transplant to death was 6 years, IQR 3–13), all of whom were hospitalised with ARDS. Overall, case fatality rate was 12% (95% CI 5% to 24%) in our population, which increased to 17% (95% CI 7% to 32%) among hospitalised patients. General characteristics of patients who did not survive, of those with ARDS and of those who were hospitalised are summarised in tables 6 and 7. Five out of the seven patients who died had a history of cancer, of whom three had an active cancer at moment of the diagnosis of COVID-19. Moreover, 9 out of 11 patients with ARDS had a clinical history for cancer. Median (IQR) lymphocyte and platelet counts (×1000/μL) were significantly lower (0.49 (0.30–0.60) vs 0.80 (0.52–1.18), p=0.030; 93 (79-110) vs 170 (104–273), p=0.044, respectively) in the group of patients who did not survive. Table 6 Characteristics of liver transplant recipients died because of COVID-19 Case Sex (M/F) Age, years Ethnicity BMI, kg/m2 Comorbidity Symptoms at presentation Immunosuppression management Respiratory support ICU admission 1 M 67 Caucasian 27.8 History of renal tumour Fever, cough, dyspnoea CNIs alone NIMV No No change 2 M 78 Caucasian 23.1 History of PTLD Fever, cough, dyspnoea CNIs alone NIMV No CV disease No change Diabetes CKD 3 M 75 Caucasian 25.1 Active tumour: HCC recurrence Dyspnoea, CNIs alone NIMV No CV disease Fatigue/myalgia No change Arterial hypertension 4 M 55 Caucasian 21.6 – Fever, dyspnoea CNIs+steroids NIMV No Only CNIs discontinuation 5 M 70 Caucasian 28.5 Active tumour: HCC recurrence Fever, dyspnoea CNIs+steroids IMV Yes Arterial hypertension Only CNIs discontinuation 6 M 66 Caucasian 23.8 Active tumour: PTLD Fever, cough, fatigue/myalgia, GI symptoms Steroids IMV Yes Arterial hypertension No change 7 F 79 Caucasian 21.3 CV disease Fever, dyspnoea, fatigue/myalgia MMF alone NC No Diabetes Arterial hypertension CKD CKD, chronic kidney disease; CNIs, calcineurin inhibitors; CV, cardiovascular; F, female; IMV, invasive mechanical ventilation; M, male; MMF, mycophenolate mofetil; NC, nasal cannula; NIMV, non-invasive mechanical ventilation; PTLD, post-transplant lymphoproliferative disorder. Table 7 General characteristics of patients who did not survive, of those with ARDS and of those who were hospitalised Outcome Overall Death (n=7) P value ARDS (n=11) P value Hospitalisation (n=41) P value Yes No Yes No Yes No Sex, male 40 (70) 6 (86) 34 (68) 0.662 10 (91) 30 (65) 0.146 29 (71) 11 (69) 0.883 Age, years, median (IQR) 65 (57–70) 70 (67–77) 62 (57–70) 0.088 68 (63–73) 62 (55–70) 0.052 65 (57–71) 60 (54–68) 0.162 BMI, kg/m2, mean (SD) 26.0 (21.4–30.6) 24.5 (21.7–27.3) 26.3 (21.4–31.2) 0.185 25.5 (21.6–28.2) 26.2 (21.3–31.1) 0.625 25.5 (29.7–21.4) 27.4 (21.6–33.2) 0.258 HCC as indication to LT 20 (35) 5 (71) 15 (30) 0.084 8 (73) 12 (26) 0.011 15 (37) 5 (31) 0.703 Very long-term LT 21 (37) 3 (43) 18 (36) 0.701 4 (36) 17 (37) 1.000 16 (39) 5 (31) 0.582 Very short-term LT 11 (19) 2 (29) 9 (18) 0.610 3 (27) 8 (17) 0.429 9 (22) 2 (13) 0.710 Smoke history 7 (14) 1 (17) 6 (14) 1.000 1 (10) 7 (15) 1.000 5 (14) 2 (14) 1.000 Cardiovascular disease 21 (37) 3 (43) 18 (36) 0.700 5 (46) 16 (35) 0.511 14 (34) 7 (44) 0.502 Arterial hypertension 32 (56) 4 (57) 28 (56) 1.000 6 (55) 27 (57) 1.000 22 (54) 10 (63) 0.544 Diabetes mellitus 21 (37) 2 (29) 19 (38) 1.000 4 (36) 17 (36) 1.000 14 (34) 7 (44) 0.502 History of cancer 24 (42) 5 (71) 19 (38) 0.119 9 (82) 15 (33) 0.005 18 (44) 6 (38) 0.659 Active cancer 5 (9) 3 (43) 2 (4) 0.011 4 (36) 1 (2) 0.004 5 (12) 0 (0) 0.308 Dyspnoea at presentation 26 (46) 6 (86) 20 (41) 0.041 9 (82) 17 (39) 0.016 22 (54) 4 (27) 0.129 Leucocytes, ×1000/μL, median (IQR) 4.51 (3.33–6.00) 2.95 (1.77–4.51) 4.70 (3.65–6.00) 0.113 3.70 (1.93–5.52) 4.70 (3.65–6.00) 0.297 4.61 (3.39–6.85) 3.85 (3.27–5.13) 0.170 Platelets, ×1000/μL, median (IQR) 160 (91–268) 93 (79–110) 170 (104–273) 0.044 102 (88–134) 183 (104–280) 0.064 164 (91–270) 149 (96–202) 0.745 Lymphocytes, ×1000/μL, median (IQR) 0.79 (0.40–1.10) 0.49 (0.30–0.60) 0.80 (0.52–1.18) 0.030 0.49 (0.40–0.76) 0.81 (0.58–1.18) 0.064 0.73 (0.45–1.00) 1.02 (0.74–1.22) 0.126 AST, U/L, median (IQR) 38 (25–53) 48 (36–80) 35 (24–52) 0.134 38 (27–57) 38 (23–53) 0.358 45 (27–57) 21 (17–29) <0.001 ALT, U/L, median (IQR) 30 (20–42) 21 (16–74) 31 (21–42) 0.602 22 (16–30) 32 (22–44) 0.142 33 (23–57) 21 (18–30) 0.026 Overall immunosuppression reduction 22 (39) 2 (29) 20 (40) 0.695 4 (36) 18 (39) 1.000 18 (44) 4 (25) 0.236 Overall immunosuppression discontinuation 4 (7) 1 (14) 3 (6) 0.417 1 (9) 3 (7) 1.000 4 (10) 0 (0) 0.568 ACE inhibitors or sartans 13 (24) 3 (50) 10 (20) 0.136 3 (30) 10 (22) 0.685 10 (25) 3 (20) 1.000 Oxygen therapy 30 (54) 7 (100) 23 (47) 0.012 11 (100) 19 (42) <0.001 29 (71) 1 (7) <0.001 Steroids (for COVID-19) 19 (35) 4 (67) 15 (31) 0.167 6 (60) 13 (29) 0.077 18 (45) 1 (7) 0.010 Antibiotics 35 (63) 7 (100) 28 (57) 0.038 10 (91) 25 (57) 0.039 30 (73) 5 (33) 0.012  >1 antibiotic 16 (29) 4 (67) 12 (24) 0.049 6 (60) 10 (22) 0.024 15 (38) 1 (6) 0.023 Antiviral 5 (9) 1 (14) 4 (8) 0.501 1 (9) 4 (9) 1.000 5 (12) 0 (0) 0.309 Hydroxychloroquine 24 (44) 3 (50) 21 (43) 1.000 5 (50) 19 (42) 0.655 22 (55) 2 (13) 0.006 ALT, alanine aminotransferase; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; BMI, body mass index; HCC, hepatocellular carcinoma; LT, liver transplantation; MMF, mycophenolate mofetil,.