Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1-2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Sequencing on an imported case in China of COVID-19 Delta variant emerging from India in a cargo ship in Zhoushan, China.

A cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was found in a cargo ship under repair in Zhoushan, China. Twelve of 20 crew members were identified as SARS-CoV-2 positive. We analyzed four sequences and identified them all in the Delta branch emerging from India with 7-8 amino acid mutation sites in the spike protein.