Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave

Abstract

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5–16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6–31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

High vaccination coverage and infection rate result in a robust SARS‐CoV‐2‐specific immunity in the majority of liver cirrhosis and transplant patients: A single‐center cross‐sectional study

“…In our cohort, anti‐NC antibodies were absent in 22% of patients despite a confirmed previous infection within a median time period of 8 months. Also, in our study, lack of anti‐NC antibodies was associated with lower anti‐S RBD levels and poor renal function, which are both risk factors for a severe course of COVID‐19 6,10,22 …”

“…4,15 Although there is no cut-off level known that offers protection, higher SARS-CoV-2 antibody levels have been demonstrated to decrease the risk of severe COVID-19 in immunocompromised patients. 10,22 Another result of this study indicating a less robust immunity in the population examined than in healthy individuals is the negative or only low T-cell response in as many as 24.6% and 20.4% of LTR and LCP, respectively. Also, there were no differences evident between infected and vaccinated patients regarding T-cell immunity determined by IGRA (Figures 3b,d).…”

“…SARS‐CoV‐2 nucleocapsid (NC) antibodies were assessed by the Elecsys anti‐NC‐SARS‐CoV‐2 Ig assay (Roche, Mannheim Germany; cut‐off ≥1 COI/mL). The spike antigen T‐cell response was determined by a commercial spike‐specific Interferon‐gamma release assay (IGRA, EUROIMMUN) and quantified according to the manufacturer's instructions with values >100 mIU/ml interpreted as low positive and values >200 mIU/ml as high‐positive as previously described 4,6,10,18 …”

Proceedings of the 28th Annual Congress of the International Liver Transplantation Society

“…A single-cohort study involving 99 LTRs was conducted to evaluate the impact of the Omicron wave on hospitalization rates, revealing that, following baseline vaccination, 11% of LTRs required hospitalization, with older age ( > 60) and comorbidities such as diabetes, hypertension, obesity, and kidney dysfunction being significant risk factors (O-046). [15] Another multicenter study analyzed graft outcomes, finding that the 90-day and 1-year allograft failure rate and overall mortality were comparable between the pre-and post COVID era (LB-0-07). In addition, the effects of vaccination on SARS-CoV-2 infection and immunological response were investigated (O-044).…”

“…The COVID-19 pandemic had a deleterious effect on liver transplant recipient (LTR) outcomes, resulting in a high risk of hospitalization, ICU admission, and mortality. A single-cohort study involving 99 LTRs was conducted to evaluate the impact of the Omicron wave on hospitalization rates, revealing that, following baseline vaccination, 11% of LTRs required hospitalization, with older age (>60) and comorbidities such as diabetes, hypertension, obesity, and kidney dysfunction being significant risk factors (O-046) 15 . Another multicenter study analyzed graft outcomes, finding that the 90-day and 1-year allograft failure rate and overall mortality were comparable between the pre- and post COVID era (LB-0-07).…”