Background Kidney transplant recipients and patients receiving hemodialysis are immunocompromised populations that are prioritized for COVID-19 vaccination but were excluded from clinical trials of SARS-CoV-2 mRNA vaccines. Antibody titers and rates of seroconversion following vaccination are lower among patients with chronic kidney disease and those taking immunosuppressants compared with controls. Data are lacking regarding their humoral response to vaccination to prevent COVID-19. Methods This investigation of early serological response after COVID-19 vaccination with the Pfizer/BioNTech (BNT162b2) mRNA vaccine included 78 patients undergoing hemodialysis, 74 kidney transplant recipients, and 7 healthy controls. We recorded data from the medical file for various clinical parameters, including response to hepatitis B vaccination, and measured antibody titers against SARS-CoV-2 at 0, 14, 28, 36 and 58 days after the first injection. Results In controls, we detected antibodies at a positive level (>13 arbitrary units per milliliter [AU/ml]) at day 14 postinjection, which increased progressively to peak at day 36 (1082 AU/ml; interquartile range [IQR], 735.0-1662.0]). Patients undergoing hemodialysis had lower titers that peaked at day 58 (276 AU/ml [IQR, 83.4-526.0]. We detected a positive antibody level in only three transplant recipients at day 36. In hemodialysis patients, those younger than 75 years had a higher antibody response versus those older than 75 years and serum albumin and Kt/V were positively correlated with serological response (P< 0.043 and P<0.019, respectively); nonresponders to HBV vaccine had the lowest anti-SARS-CoV-2 antibody titers. Conclusions Our results suggest that the postvaccination humoral response is strongly inhibited by immunosuppressant therapy in kidney transplant recipients and is reduced by the uremic condition in patients undergoing hemodialysis.

These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.

Human cytomegalovirus (HCMV) is responsible for life-threatening infections in immunocompromised individuals and can cause serious congenital malformations. Available antivirals target the viral polymerase but are subject to cross-resistance and toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed. During HCMV replication, DNA maturation and packaging are performed by the terminase complex, which cleaves DNA to package the genome into the capsid. Identified in herpesviruses and bacteriophages, and with no counterpart in mammalian cells, these terminase proteins are ideal targets for highly specific antivirals. A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials, but the mechanism of action is unclear. Letermovir has no significant activity against other herpesvirus or non-human CMV. This review focuses on the highly conserved mechanism of HCMV DNA-packaging and the potential of the terminase complex to serve as an antiviral target. We describe the intrinsic mechanism of DNA-packaging, highlighting the structure-function relationship of HCMV terminase complex components.

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