Efficacy and safety of the SARS-CoV-2 mRNA vaccine in lung transplant recipients: a possible trigger of rejection.

OBJECTIVE: Solid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown. METHODS: We performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination. RESULTS: There were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9-10.2) vs 2.8 (1.9-4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250-500) vs 1000 (1000-1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients. CONCLUSIONS: The antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination.

The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19.

INTRODUCTION: Transplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs. METHODS: Forty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O2) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab. RESULTS: Casirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O2 ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763-0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878-0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511-0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205-0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3-5 days after hospitalization than in those without, at 7-9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL). CONCLUSION: Casirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression.

A Comparative Study on the Variation in Seropositivity Rates After 2-Dose COVID-19 Vaccination Before or After Transplant: A Single-Center Analysis.

OBJECTIVES: Many researchers have demonstrated that the seropositivity rate after SARS-CoV-2 coronavirus vaccination is lower in patients receiving oral immunosuppressants. In this article, we report on a comparative study on the seropositivity rate after 2 doses of coronavirus vaccine before or after kidney transplant. MATERIALS AND METHODS: We studied 111 recipients vaccinated after transplant, 19 patients vaccinated before transplant, and 10 healthy patients. We retrospectively measured antibody titers using preserved serum samples. The antibody testing was performed 1 month and 3 months after vaccination. The measurement was via LABScreen COVID Plus, which enables simultaneous determination of 5 coronavirus protein antigens. RESULTS: Seropositivity to coronavirus antibodies was observed in all 19 patients vaccinated before transplant (100%) and in all the 10 healthy patients (100%). Forty- six of the 111 recipients (42%) vaccinated after transplant developed seropositivity. Analyzed at each time point after vaccination, the mean fluorescence intensity of antibodies was unchanged between 1 month and 3 months after vaccination in transplant recipients who were vaccinated after transplant and developed seropositivity. On the other hand, the antibody mean fluorescence intensity in patients vaccinated before transplant was markedly lower at 3 months (posttransplant). CONCLUSIONS: All patients with renal failure who were vaccinated before transplant showed a high seropositivity rate, similar to that in healthy patients. The seropositivity rate for each of the viral fragment antibodies in patients vaccinated before transplant was maintained, as seen in healthy patients. However, in patients vaccinated before transplant who tested positive for antibody production at 1 month after vaccination,the antibody mean fluorescence intensity at 3 months after vaccination (posttransplant) was remarkedly lower than the mean fluorescence intensity at 1 month, which was probably caused by the types of immunosuppressive regimens used atthe time of transplant.