Protective measures against Omicron could be more effective than Evusheld in liver transplant recipients.

Evusheld (the combination of cilgavimab and tixagevimab, two long-lasting monoclonal antibodies against SARS-CoV-2) has been approved by the FDA as a pre-exposure treatment for COVID-19 in immunocompromised patients older than 12 years. However, this monoclonal antibody has been developed from SARS-CoV-2 variants that were predominant at the beginning of the pandemic, when Ómicron was not prevalent. Compared with other solid organ transplant recipients, liver transplant recipients have shown an excellent immune response to standard vaccination with three doses of the SARS-CoV-2 vaccine. In addition, this population has shown very good adherence to protective measures for the transmission of COVID-19 infection. Several studies have shown that the use of Evusheld is less effective against Ómicron than against other variants of SARS-CoV-2. In addition, in the post-hoc analysis, it appears to be a drug that increases cardiovascular risk. For these reasons, we believe that in liver transplant recipients is essential to prioritize vaccination and protective measures, rather than the use of Evusheld as pre-exposure prophylaxis.

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

BACKGROUND: Since the declaration of a new variant of concern (VOC), Omicron, by the World Health Organization in November 2021, a quick spread has been documented worldwide, being the main VOC in the sixth wave in Spain. The Omicron variant has more transmissibility, lower virulence, and less risk of severe disease than previously described VOC. Here we analyze the current wave of severe acute respiratory syndrome coronavirus 2 infection in liver transplant recipients (LTRs). METHODS: A retrospective observational study of 355 LTRs was conducted in La Rioja and Cantabria regions of Spain. Epidemiological and clinical parameters were gathered on the basis of clinical records and telephone interviews. RESULTS: In the current wave of infection, a higher number of LTRs have been found to be infected than the sum of the previous 5 waves (30 versus 16 LTRs). Of the 30 infected LTRs, 29 (96.6%) had received 3 vaccine doses (mRNA based), in a median of 93 d (interquartile range, 86-108) before infection. Eight of 30 LTRs (24.0%) were asymptomatic and 21 LTRs (67.8%) were with mild symptoms with a mean duration of 4.6 d (interquartile range, 2.5-7), whereas in the unvaccinated LTRs, the symptoms were fever, nausea, vomiting, and diarrhea. Moreover, in the sixth wave, intrafamiliar transmission was the main route of infection (17/30; 56.6%), and nosocomial transmission was confirmed in 2 LTRs (6.6%). CONCLUSIONS: In our series, increased transmissibility of the Omicron variant was confirmed, including nosocomial infection, with a lower risk of severe disease in LTRs. These findings could be supported by the universal vaccination of LTRs and less virulence of the Omicron variant.

Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.

Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 µg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.

Impact of the COVID-19 lockdown on liver transplant recipients. A single center observational study.

BACKGROUND: the impact of the COVID-19 outbreak and lockdown on liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period. METHODS: a web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit between August and October 2020. This pseudonymized survey explored demographic and lifestyle variables (i.e., eating and physical habits), disruptions in routine medical care, different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of COVID, resilience, etc.) and health perception using different validated instruments. RESULTS: altogether, 48.7 % (116 of 238) LT recipients accepted to participate in the study, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4 % presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5 % exhibited moderate/severe insomnia and only 10.5 % moderate/severe depression. Forty patients (38.5 %) gained weight, 24 % experienced a worsening in their eating habits and 63.4 % referred to practicing less or much less exercise during the lockdown. Only 25 % perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9 %) or poor adherence to therapy (1.9 %) were exceptional. CONCLUSIONS: COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear.

Feasibility of large-scale population testing for SARS-CoV-2 detection by self-testing at home.

The simplicity and low cost of rapid point-of-care tests greatly facilitate large-scale population testing, which can contribute to controlling the spread of the COVID-19 virus. We evaluated the applicability of a self-testing strategy for SARS-CoV2 in a population-based, cross-sectional study in Cantabria, Spain, between April and May 2020. For the self-testing strategy, participants received the necessary material for the self-collection of blood and performance of a rapid antibody test using lateral flow immunoassay at home without the supervision of healthcare personnel. A total of 1,022 participants were enrolled. Most participants correctly performed the COVID-19 self-test the first time (91.3% [95% CI 89.4-92.9]). Only a minority of the participants (0.7%) needed the help of healthcare personnel, while 6.9% required a second kit delivery, for a total valid test result in 96.9% of the participants. Incorrect use of the self-test was not associated with the educational level, age over 65, or housing area. Prevalence of IgG antibodies against SARS-CoV2 for subjects with a valid rapid test result was 3.1% (95% CI 2.2-4.4), similar to the seroprevalence result obtained using a conventional approach carried out by healthcare professionals. In conclusion, COVID-19 self-testing should be considered as a screening tool.

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients.

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.