Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports

Table 1 Details of the three cases reported

	Case 1	Case 2	Case 3
Age (yr)	61	68	62
Sex	Female	Male	Female
LT indication	Cryptogenic cirrhosis	NASH	Primary biliary cholangitis
Date of liver transplant	September 7, 2019	March 3, 2020	February 13, 2019
Immunosuppression (per day)	Tacrolimus 5 mg and prednisone 5 mg	Tacrolimus 7 mg, mycophenolic acid 2000 mg, prednisone 20 mg	Tacrolimus 3 mg, mycophenolic acid 2000 mg, prednisone 5 mg
Blood concentration of tacrolimus (before COVID-19)	7 ng/mL	7.5 ng/mL	5.2 ng/mL
Allograft function (before COVID-19)	Normal	Normal	Increased GGT and ALP
Comorbidities	Hypothyroidism	Diabetes, hypertension, stroke	Hypertension
Laboratory test1:
PaO2: FiO2 ratio (while IMV)	237 (76-376)	367 (337-385)	256 (133-329)
White-cell count (× 103/UL)	4.50 (2.38-9.87)	6.61 (1.8-17.4)	15.71 (7.02-36.14)
Lymphocyte count (× 103/UL)	0.30 (0-0.65)	0.325 (0.2-1.02)	1 (0.54-2.01)
Platelet count (× 103/UL)	9.5 (3-38)	113.5 (37-372)	290 (158-406)
Hemoglobin (g/DL)	8.7 (6.5-9.4)	9.2 (7-11.8)	10.4 (7.6-12.9)
Il-6 (pg/mL)	599 (400-799)	558 (192-1000)	54 (50-286)
C-reactive protein (mg/DL)	10.3 (8.2-18.3)	4 (0.4-13.3)	1.8 (0.7-4.6)
Procalcitonin (ng/mL)	2.2 (1.1-7.8)	0.25 (0.12-0.43)	0.28 (0.17-0.75)
Ferritin (ng/mL)	5338 (814-9862)	1262 (392-2095)	2047 (1360-2297)
Lactate dehydrogenase (U/L)	452 (209-649)	265 (161-378)	399 (165-646)
Aspartate aminotransferase (U/L)	126 (29-466)	14 (9-36)	30 (16-44)
Alanine aminotransferase (U/L)	89 (29-197)	21 (8-31)	24 (5-98)
Total bilirubin (mg/DL)	1.2 (0.3-2.65)	0.56 (0.39-1.23)	1.82 (0.21-4)
Creatine kinase (U/L)	14 (10-18)	13 (7-75)	29 (29-36)
Creatinine (mg/DL)	0.69 (0.45-1.07)	1.22 (1.04-1.93)	0.89 (0.54-2.65)
D-dimer (ng/mL)	1073 (565-1825)	1347 (620 - 3431)	283 (153-648)
Sodium (meq/L)	137 (128-141)	139 (136 - 163)	141 (135-145)
Potassium (meq/L)	4.6 (2.9-5.8)	4 (3.3-4.9)	4 (3.2-5.2)
Chloride (meq/L)	102 (97-105)	103 (100-111)	107 (99-112)
RT-PCR of SARS-CoV-2	Negative on day 3; positive on day 6	Negative on day 8; positive on days 13, 36, 42, 47, 54, 65 and 79	Negative on days 14, 72 and 75; positive on days 26, 42 and 55
Radiologic findings	Bilateral pneumonia, pleural effusion	Bilateral pneumonia, peripheral ground-glass opacity, pleural effusion	Bilateral pneumonia, peripheral ground-glass opacity
Treatment	HCQ (200 mg daily), azithromycin (250 mg daily), LPV/r (one dose 400/100 mg), vancomycin (1 g daily)	HCQ (200 mg daily), azithromycin (250 mg daily), tocilizumab (one dose 8 mg/kg), methylprednisolone (180 mg three doses)	HCQ (200 mg daily), azithromycin (250 mg daily), tocilizumab (one dose 8 mg/kg), methylprednisolone (60 mg daily), vv-ECMO
Immunosuppressant dose reduction	Yes (low dose of tacrolimus)	Yes (mycophenolic acid suspended and low dose of tacrolimus)	Yes (mycophenolic acid suspended)
Rejection during or after COVID-19	No	No	Yes
Complications	Secondary Enterococcus faecalis (BAL culture) lung infection	Asymptomatic intra-abdominal collection	Tracheoesophageal fistula

¹Expressed as the median and range, of the analytical values since the RT-PCR of SARS-CoV-2 was positive until present. ALP: Alkaline phosphatase; BAL: Bronchoalveolar lavage; GGT: Gamma-glutamyltransferase; HCQ: Hydroxychloroquine; ICU: Intensive care unit; IMV: Invasive mechanical ventilation; LPV/r: Lopinavir/ritonavir; NASH: Non-alcoholic steatohepatitis; NE: Norepinephrine; RT-PCR: Reverse transcription polymerase chain reaction; vv-ECMO: Venovenous extracorporeal membrane oxygenation.