SARS-CoV-2 and Liver Transplant: How Has It Behaved in This Sixth Wave? : Transplantation

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Original Clinical Science—General

SARS-CoV-2 and Liver Transplant: How Has It Behaved in This Sixth Wave?

Odriozola, Aitor MD1; San Segundo, David PhD2; Cuadrado, Antonio PhD1; Hernáez, Tania MD3; Escrich, Víctor MD3; Fortea, José Ignacio PhD1; Martínez, Ángela MD3; Puente, Ángela PhD1; Lapeña, Berta MD3; del Barrio, María MD1; López-Hoyos, Marcos PhD2; Crespo, Javier PhD1; Fábrega, Emilio PhD1

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Transplantation 106(7):p 1445-1449, July 2022. | DOI: 10.1097/TP.0000000000004157
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Since its declaration by the World Health Organization and the European Centre for Disease Prevention and Control on November 26, 2021, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern called (B.1.1.529)1,2 was first detected in South Africa. This variant of concern has experienced rapid expansion and was estimated to be 81% of the variants isolated by November 2021 and 95% isolated by December 2021. In fact, Omicron was the most predominant variant of the sixth wave in Spain.3 Accumulating scientific evidence supports the increased transmissibility of the Omicron variant and its greater immune escape capacity, as well as lower virulence and lower risk of causing severe disease and death than previous variants.4 This study aimed to analyze the impact of SARS-CoV-2 infection on liver transplantation in the current wave from late November 2021 through February 23, 2022.


This retrospective observational study included 355 liver transplant recipients (LTRs) from La Rioja and Cantabria undergoing regular follow-up at the Liver Transplant Unit of the Marqués de Valdecilla University Hospital and the Hepatology Unit of San Pedro Hospital. Clinical data, including comorbidities and immunosuppressive regimen, were obtained from patient’s medical records. Epidemiological and clinical information, including contact details, date onset, clinical severity, and disease course of SARS-CoV-2 infection, was gained via telephone survey. This study was approved by the Institutional Ethics Committee of Cantabria (Code 2022.038) and complied with the provisions of the Good Clinical Practice guidelines and the Declaration of Helsinki. The humoral response was evaluated using serum levels of anti–SARS-CoV-2 spike protein S1 immunoglobulin (Abbott SARS-CoV-2 antispike immunoglobulin G II assay, positive >50 AU/mL), and serum levels of anti–SARS-CoV-2 spike protein S1 immunoglobulin of ≥4160 AU/mL were chosen as surrogate measures of antibody neutralization.5 Categorical variables were expressed as the number of cases (percentage), and continuous variables were expressed as the median (interquartile range [IQR]).


In the current sixth wave, more LTRs have been found to be infected than the sum of the 5 previous waves (30 versus 16 LTRs; Figure 1). Table 1 shows the characteristics of these patients. Of these 30 LTRs, 29 were full vaccinated (96.6%) and received a third dose of Pfizer or Moderna mRNA vaccine between September 20, 2021, and December 27, 2021, in a median of 96 d (IQR, 87–111) before the diagnosis of the infection (from December 2, 2021, to February 17, 2022). It is noteworthy that the infection was asymptomatic in 8 LTRs (24%), the symptoms were mild in 21 LTRs (70%), and only 1 patient required hospitalization for pneumonia and finally died. The most common symptoms were cough (36.6%) and runny/stuffy nose (36.6%), followed by headache (23.3%), myalgia (20%), and fatigue (16.6%) with a mean duration of 4.6 d (IQR, 2.5–7). Whereas in the nonvaccinated patient, these symptoms were accompanied by fever, nausea, vomiting, and diarrhea. In a subgroup of 19 LTRs, we had the results of the humoral response in a median of 107 d (IQR, 93.75–119) after the third vaccine dose. Paradoxically, we observed in the LTRs with lower anti-S1 antibody titers (<4160 U/mL) more asymptomatic patients (4/8; 50%) than in the group of LTRs with a stronger humoral response (2/11; 18.1%), suggesting the possibility that LTRs developed cellular response capable of preventing or limiting severe coronavirus disease 2019 symptoms.6 In contrast, of the 16 LTRs infected in the previous waves, 5 (31.25%) required hospital admission for pneumonia, and 2 of them (12.5%) died. In this sixth wave, intrafamilial transmission (17/30; 56.6%) was the main route of infection, and nosocomial transmission was demonstrated in 2 LTRs (6.6%). In 16 LTRs (53.3%), the initial diagnosis was made by a rapid antigen self-test taken at home7,8 and subsequently confirmed by antigen test or by reverse transcription polymerase chain reaction, performed with nasopharyngeal swab in primary care centers. The outpatient follow-up protocol was similar to that of patients without any risk factors: without sending any patient to the hospital, neither performing blood tests nor chest radiology. In fact, only 12 LTRs (40%) contacted the Liver Transplant Unit.

TABLE 1. - Epidemiological and clinical data of liver transplant recipients in the sixth wave of SARS-CoV-2 infection
S. No. Age Sex Transplant Date of liver transplant Comorbidities Immunosuppressive regimen Date of third dose Anti-S1 (AU/mL) Date of infection Transmission Autotest Symptoms Duration Days since vaccination Hospitalization Following Death
1 74 Female Liver 21/07/2012 Diabetes, hypertxension, CKD3a Tacrolimus 09/27/2021 (Moderna) 12/24/2021 Intrafamiliar Yes Cough, runny/stuffy nose 5 88 No Primary care No
2 45 Male Liver 17/01/2015 Ulcerative colitis Tacrolimus + MMF + P 10/03/2021 (Moderna) 12/02/2021 Intrafamiliar No Cough, runny/stuffy nose 5 60 No Primary care No
3 65 Male Liver 16/03/2015 Diabetes, hypertension, celiac disease Tacrolimus 09/27/2021 (Pfizer) 12/22/2021 Intrafamiliar No Cough, headache 3 86 No Primary care No
4 47 Male Liver 08/11/2015 None Tacrolimus 10/05/2021 (Moderna) 12/30/2021 Unknown Yes Runny/stuffy nose, headache 2 86 No Primary care No
5 67 Male Liver 15/02/2018 Diabetes, CKD 3a, CVD Tacrolimus + EV 09/22/2021 (Moderna) 12/28/2021 Unknown No Cough, headache 3 97 No Primary care No
6 64 Male Liver 02/03/2015 Diabetes, CKD2 Tacrolimus 09/20/2021 (Pfizer) 26/12/2021 Intrafamiliar Yes Asymptomatic 0 97 No Primary care No
7 65 Male Liver 07/12/2002 Diabetes, hypertension MMF 12/27/2021 (Moderna) 01/10/2022 Unknown Yes Fever, myalgias, fatigue 10 14 No Primary care No
8 72 Male Liver 20/09/2015 Diabetes, hypertension, CKD3a Tacrolimus 09/28/2021 (Moderna) 39 975 01/03/2022 Unknown No Asymptomatic 0 97 No Primary care No
9 48 Male Liver 06/10/2020 Diabetes, CKD2 Tacrolimus + EV 09/29/2021 (Moderna) 461 01/11/2022 Intrafamiliar No Asymptomatic 0 104 No Primary care No
10 72 Male Liver 15/12/2005 Diabetes, hypertension, CKD 4 MMF 09/28/2021 (Moderna) 10 665 01/11/2022 Intrafamiliar Yes Cough, runny/stuffy nose 5 105 No Primary care No
11 58 Male Liver 24/07/2015 Hypertension obesity EV 09/29/2021 (Moderna) 12 513 12/31/2021 Social Yes Myalgias, fatigue 8 93 No Primary care No
12 69 Male Liver 31/08/2009 CVD Tacrolimus 10/05/2021 (Moderna) 29 164 01/09/2022 Unknown Yes Cough, runny/stuffy nose 5 96 No Primary care No
13 51 Female Liver 10/05/2012 Polycythemia vera, CKD3a Tacrolimus + MMF + P 09/28/2021 (Moderna) 21 019 01/09/2022 Intrafamiliar Yes Headache, sore throat, fatigue 6 103 No Primary care No
14 35 Male Liver 23/02/2018 None Tacrolimus 09/28/2021 (Moderna) 40 000 01/12/2022 Intrafamiliar Yes Runny/stuffy nose, headache 7 106 No Primary care No
15 67 Male Combined liver and kidney 30/12/2006 Diabetes, hypertension Tacrolimus + MMF 09/27/2021 (Moderna) 33 01/11/2022 Unknown Yes Cough, runny/stuffy nose, nausea 7 106 No Primary care No
16 70 Female Liver 24/11/2020 Diabetes, hypertension, CKD3a Tacrolimus + MMF + P 09/28/2021 (Moderna) 853 01/16/2022 Intrafamiliar Yes Cough, headache, fatigue, myalgias 7 110 No Primary care No
17 65 Male Liver 06/08/2015 Obesity, CKD3b Tacrolimus + MMF 09/28/2021 (Moderna) 25 452 01/17/2022 Unknown No Runny/stuffy nose 5 111 No Primary care No
18 72 Female Liver 24/05/2018 Diabetes, hypertension, obesity Tacrolimus 10/28/2021 (Moderna) 2706 01/14/2022 Social No Fatigue 1 78 No Primary care No
19 65 Male Liver 12/05/2012 Diabetes, hypertension, CVD, CPD Tacrolimus 18/10/2021 (Pfizer) 19 937 24/12/2021 Nosocomial No Asymptomatic 0 67 No Primary care No
20 74 Male Combined liver and kidney 26/02/2007 Diabetes, hypertension, CKD4 Tacrolimus + MMF 11/22/2021 (Pfizer) 12/31/2021 Intrafamiliar No Fever, cough, headache, diarrhea, pneumonia 46 69 Yes Intensive care unit Yes
21 77 Male Liver 01/07/2007 Diabetes, CKD3a Tacrolimus + MMF + P 10/26/2021 (Pfizer) 01/12/2022 Nosocomial No Asymptomatic 0 78 No Primary care No
22 59 Male Liver 01/05/2007 Diabetes, CKD3a MMF 09/27/2021 (Moderna) 1042 01/24/2022 Unknown No Asymptomatic 0 119 No Primary care No
23 66 Male Liver 14/11/2016 None Tacrolimus 10/19/2021 (Moderna) 1467 01/15/2022 Intrafamiliar No Asymptomatic 0 88 No Primary care No
24 39 Female Liver 13/05/2016 None Tacrolimus + azathioprine 11/16/2021 (Pfizer) 01/16/2022 Intrafamiliar Yes Runny/stuffy nose 2 61 No Primary care No
25 64 Male Liver 04/04/2018 Hypertension EV 10/05/2021 (Moderna) 40 000 02/02/2022 Intrafamiliar Yes Myalgias 2 120 No Primary care No
26 66 Female Liver 22/10/2011 None Tacrolimus + MMF 10/05/2021 (Moderna) 40 000 12/31/2021 Intrafamiliar Yes Cough, sore throat, headache, myalgias 7 87 No Primary care No
27 65 Female Liver 07/04/2019 Hypertension, CKD3a Tacrolimus Not vaccinated 20/01/2021 Intrafamiliar No Fever, headache, sore throat, nausea, vomiting, diarrhea 7 No Primary care No
28 56 Male Liver 23/03/2011 CKD2 Tacrolimus 10/05/2021 (Moderna) 1304 02/04/2022 Intrafamiliar Yes Asymptomatic 0 122 No Primary care No
29 58 Male Liver 25/04/2021 Diabetes Tacrolimus 09/27/21 (Moderna) 85 02/15/2022 Unknown No Cough, runny/stuffy nose, sore throat, 5 141 No Primary care No
30 36 Female Liver 06/06/1995 None Tacrolimus 09/28/2021 (Moderna) 39 242 02/17/2022 Intrafamiliar Yes Runny/stuffy nose, diarrhea 2 142 No Primary care No
CKD, chronic kidney disease categories according to KDIGO; CPD, chronic pulmonary disease; CVD, cardiovascular disease; EV, everolimus; KDIGO, Kidney Disease: Improving Global Outcomes; MMF, mycophenolate mofetil; P, prednisone.

Evolution of SARS-CoV-2 infection since the pandemic declaration in the general population and liver transplant recipients from Cantabria and la Rioja. The timeline of the frequency of new cases of SARS-CoV-2 infection in the general population (black circles) and liver transplant recipients (gray circles) are depicted. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.


In our series, the route of transmission was mainly intrafamilial, although we also observed nosocomial transmission because of the high rate of community transmission of the virus in this wave. It is noteworthy that asymptomatic cases represented 56.6% of all infected LTRs, percentage higher than reported by the Prevalence of SARS-CoV-2 in Spain study performed in the last months of the first wave in Spain.9 Additionally, we confirmed that in this sixth wave, there is a greater transmissibility of the infection with a lower risk of producing serious illness in LTRs. This may be because of the practically universal vaccination with 3 vaccine doses of the LTRs together with the lower virulence of the Omicron variant. These findings together with those reported from South Africa, United Kingdom, and Canada, are consistent with experimental animal infection that Omicron causes less severe disease in mice and hamsters.4,10


1. World Health Organization (WHO). Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern. 2021. Available at Accessed December 6, 2021.
2. European Centre for Disease Prevention and Control (ECDC). Threat assessment brief: implications of the further emergence and spread of the SARS CoV 2 B.1.1.529 variant of concern (Omicron) for the EU/EEA- first update. 2021. Available at Accessed December 6, 2021.
3. Government of Spain, Ministry of Health. Actualización de la situación epidemiológica de las variantes de SARS-CoV-2 en España. 2022. Available at Accessed March 30, 2022.
4. Wolter N, Jassat W, Walaza S, et al. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa: a data linkage study. Lancet. 2022;399:437–446.
5. Ebinger JE, Fert-Bober J, Printsev I, et al. Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2. Nat Med. 2021;27:981–984.
6. GeurtsvanKessel CH, Geers D, Schmitz KS, et al. Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients. Sci Immunol. 2022;7:eabo2202.
7. Iruzubieta P, Fernández-Lanas T, Rasines L, et al. Feasibility of large-scale population testing for SARS-CoV-2 detection by self-testing at home. Sci Rep. 2021;11:9819.
8. Drain PK. Rapid diagnostic testing for SARS-CoV-2. N Engl J Med. 2022;386:264–272.
9. Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al.; ENE-COVID Study Group. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020;396:535–544.
10. Bentley EG, Kirby A, Sharma P, et al. SARS-CoV-2 Omicron-B.1.1.529 variant leads to less severe disease than Pango B and Delta variants strains in a mouse model of severe COVID-19. bioRxiv. Preprint posted online December 30, 2021.. doi:2021.2012.2026.474085

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