COVID‐19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS‐CoV‐2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer‐BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS‐CoV‐2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti‐spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17–2.69]), high‐dose corticosteroids in the last 12 months (1.3 [1.09–1.86]), maintenance with triple immunosuppression (1.43 [1.06–2.15]), and regimen that includes mycophenolate (1.47 [1.26–2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID‐19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.

Background and aims Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. Methods LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. Results Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. Conclusion LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. Lay summary Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive , average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

Summary DNA interstrand crosslinks (ICLs) are the most toxic lesions induced by chemotherapeutic agents such as Mitomycin C and Cisplatin. By covalently linking both DNA strands, ICLs prevent DNA melting, transcription, and replication. Studies on ICL signaling and repair have been limited because these drugs generate additional DNA lesions that trigger checkpoint signaling. Here, we monitor sensing, signaling from and repairing of a single, site-specific ICL in cell-free extract derived from Xenopus eggs and in mammalian cells. Notably, we demonstrate that ICLs trigger a checkpoint response independently of origin-initiated DNA replication and uncoupling of DNA polymerase and DNA helicase. The Fanconi anemia pathway acts upstream of RPA-ATR-Chk1 to generate the ICL signal. The system also repairs ICLs in a reaction that involves extensive, error-free, DNA synthesis. Repair occurs by both origin-dependent and origin-independent mechanisms. Our data suggest that cell sensitivity to crosslinking agents results from both checkpoint and DNA repair defects.