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.

Keywords: COVID-19; SARS-CoV-2; VOC Omicron; liver transplant recipients; post-acute COVID-19 syndrome.

Figure 1

Symptoms and duration of SARS-CoV-2 breakthrough infections. (A): Percentage of LTR (n = 80) reporting long-lasting symptoms: subdivided into osCOV-19 (4–12 weeks) and postCOV-19 (>12 weeks). (B): Reported long-lasting symptoms in LTR (n = 30). Abbreviations: osCOV-19: ongoing symptomatic COVID-19; postCOV-19: post-COVID-19 syndrome; w: weeks.

Figure 2

Humoral and cellular immune response in LTR and HC after SARS-CoV-2 infection. (A): Percentages of anti-S RBD titers in LTR, and HC between <0.4, <100, 100–10³, 10³–10⁵, and >10⁵ Arbitrary Units (AU)/mL. (B): Scattergram presenting individual anti-S RBD levels of LTR, and HC. (C): Percentages of LTR, and HC showing a negative (<100 mlU/mL), low positive (100–200 mlU/mL,) and high positive (>200 mlU/mL) Spike-specific T cell response as measured by IFN-γ release. (D): Scattergram with individual interferon-gamma (IFN-γ) levels afterSARS-CoV-2 breakthrough infection. (E): Evolution of anti-S RBD levels in LTR for whom samples were available before and after SARS-CoV-2 infection. (F): Correlation of humoral and cellular immune response in LTR (n = 37) and HC (n = 18). Dotted lines indicate cut-off values for IFN-γ (>200 mlU/mL) and anti-S-RBD (>10³ AU/mL) levels. Statistical Analysis was performed by Mann–Whitney Test (B, D) or Wilcoxon-signed-rank-test (E). Dotted lines indicate previously defined cut-off values. Dots and triangles were used to represent LTR, and HC, respectively. Ns and *** represent p-value > 0.05 and p-value < 0.0005, respectively.

Figure 3

Humoral immune response prior to SARS-CoV-2 infection according to disease severity. (A): Percentages of anti-S RBD titers pre-COVID-19 in LTR with COVID-19 breakthrough infections requiring hospitalization and those not-requiring hospitalization. (B): Scattergram of individual anti-S RBD titers in LTR with COVID-19 breakthrough infections requiring hospitalization and those not requiring hospitalization. Patients with severe disease (n = 3) according to the NIH guidelines are presented by an open circle and patients with critical disease (n = 2) by a diamond. Statistical Analysis was performed by Mann–Whitney Test, * represents a p-value below <0.05.