INTRODUCTION:

The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT).

OBJECTIVES:

We aimed to assess a cohort of transplant recipients who developed COVID‑19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes.

PATIENTS AND METHODS:

During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS‑CoV‑2 infection. Baseline and follow‑up data on graft function, immunosuppression, and patient and graft outcomes were assessed.

RESULTS:

Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS‑CoV‑2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ‑19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID‑19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients.

CONCLUSIONS:

In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID‑19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS‑CoV‑2 infection.

BACKGROUND & AIMS:

In the context of the Italian severe acute respiratory syndrome coronavirus 2 vaccination program, liver transplant (LT) recipients were prioritized for vaccine administration, although the lower response to vaccines is a well-known problem in this population. We aimed to evaluate immunogenicity of BNT162b2 mRNA vaccine in LT recipients and healthy controls and to identify factors associated with negative response to vaccine.

METHODS:

In a cohort of adult patients with LT, we prospectively evaluated the humoral response (with anti-Spike protein IgG-LIAISON SARS-CoV-2 S1/S2-IgG chemiluminescent assay) at 1 and 3 months after 2-dose vaccination. A group of 307 vaccinated health care workers, matched by age and sex, served as controls.

RESULTS:

Overall, 492 LT patients were enrolled (75.41% male; median age, 64.85 years). Detectable antibodies were observed in the 75% of patients, with a median value of 73.9 AU/mL after 3 months from 2-dose vaccination. At multivariable analysis, older age (>40 years; P = .016), shorter time from liver transplantation (<5 years; P = .004), and immunosuppression with antimetabolites (P = .029) were significantly associated with non-response to vaccination. Moreover, the LT recipients showed antibody titers statistically lower than the control group (103 vs 261 AU/mL; P < .0001). Finally, in both controls and LT patients, we found a trend of inverse correlation between age and antibody titers (correlation coefficients: -0.2023 and -0.2345, respectively).

CONCLUSIONS:

Three months after vaccination, LT recipients showed humoral response in 75% of cases. Older age, shorter time from transplantation, and use of antimetabolites were factors associated with non-response to vaccination, and LT recipients at risk of non-response to vaccination needed to be kept under close monitoring.

OBJECTIVES:

The recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.

METHODS:

This was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.

RESULTS:

Of the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients.

DISCUSSION:

A third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

INTRODUCTION:

Decreased immunosuppression has been proposed for kidney transplant recipients infected with coronavirus disease 2019 (COVID-19), but the impact on the alloreactive immune response during and after infection has been poorly investigated. We evaluated the occurrence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSAs) (post-COVID-19) and rejection episodes after COVID-19 with particular focus on immunosuppression modulation.

METHODS:

Kidney transplant recipients from 2 French institutions had anti-HLA antibody screening before and after COVID-19. Management of immunosuppression, rejection episodes, COVID-19 severity, inflammatory markers, and antiviral therapies were recorded.

RESULTS:

From 251 recruited patients, 72 were excluded because of COVID-19-related death (n = 25) and incomplete immunologic follow-up (n = 47). Among the remaining 179 included patients, almost half were hospitalized (49.2%). Antimetabolites were interrupted in 47% of patients (82% in hospitalized, median time of resumption of 23 days and in 15% nonhospitalized, median time of resumption of 7 days). Calcineurin inhibitors were interrupted in 12% of patients (all hospitalized, median time of resumption of 11 days). The incidence of post-COVID-19 DSA was 4% (8% and 0% in hospitalized and nonhospitalized, respectively). Allograft rejection occurred in 3 patients (1.7%) and all were hospitalized. Younger age, transplantation <1 year, and preexisting DSA were more frequently observed in patients with post-COVID-19 DSA, whereas inflammatory markers, lymphopenia, and use of antiviral therapies were not.

CONCLUSION:

The incidence of post-COVID-19 DSA among COVID-19-positive kidney transplant recipients was low (4%) despite a significant decrease in immunosuppression and was mainly restricted to high-risk immunologic patient's status. COVID-19 severity was not associated with post-COVID-19 DSA and/or rejection.

Kidney transplant recipients (KTRs) have reduced ability to mount adequate antibody response after two doses of the COVID-19 mRNA vaccine. French health authorities have allowed a third booster dose (D3) for KTRs, but their response is heterogeneous and tools able to discriminate the responders are lacking. Anti-RBD IgG titers (chemiluminescence immunoassay), spike-specific cellular responses (IFN-γ-releasing assay, IGRA), and in vitro serum neutralization of the virus (the best available correlate of protection), were evaluated 7-14 days after the second dose (D2) of BNT162b2 vaccine in 93 KTRs. Among the 73 KTRs, whose serum did not neutralize SARS-CoV-2 in vitro after D2, 14 (19%) acquired this capacity after D3, and were considered as "responders." Exploratory univariate analysis identified short time from transplantation and high maintenance immunosuppression as detrimental factors for the response to D3. In addition, any of the presence of anti-RBD IgGs and/or positive IGRA after D2 was predictive of response to D3. By contrast, none of the KTRs with both a negative serology and IGRA responded to D3. In summary, routinely available bioassays performed after D2 allow identifying KTRs that will respond to a booster D3. These results pave the way for the personalization of vaccination strategy in KTRs.

Little is known about immunogenicity after ChAdOx1 nCov-19 vaccination after transplantation. We assessed the vaccine response by antibody testing, surrogate neutralization test (sVNT) against wild-type (WT) and delta variant (DT), and T cell assay in 83 kidney transplant recipients (KTRs) and 52 healthy volunteers (HVs). For KTRs, a positive anti-RBD antibody was seen in 2.8% after one dose and 15.7% after two doses of the vaccine. After two doses, the positivity rate by sVNT was equal (4.9% each, for WT and DT) and was 13.4% by T cell response. Post two doses, KTRs had significantly lower geometric mean titer than HVs (1.93 [95% CI: 1.39-2.69] vs. 248.3 [95% CI: 203.7-302.6] BAU/ml, respectively, p < .001). Daily mycophenolate dose of ≥1000 mg significantly associated with negative seroconversion [risk ratio (RR) of 0.33, 95% CI: 0.15-0.72, p = .005]. Compared with cyclosporine, daily tacrolimus dose of ≤3 mg and >3 mg of tacrolimus significantly associated with negative seroconversion [RR = 0.38 (95% CI, 0.17-0.85, p = .018) and RR = 0.16 (95% CI, 0.37-0.73, p = .018)], respectively. The vaccine was safe and well-tolerated but the immune response after the two doses of ChAdOx1 nCov-19 vaccine in KTRs was very low.