The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.

• Klíčová slova
• COVID-19, antibody response, immunogenicity, lung transplantation, mRNA vaccine,
• MeSH
• COVID-19 prevence a kontrola   MeSH
• imunogenicita vakcíny * MeSH
• lidé středního věku MeSH
• lidé MeSH
• pooperační komplikace prevence a kontrola   virologie   MeSH
• transplantace plic * MeSH
• tvorba protilátek MeSH
• vakcína BNT162 MeSH
• vakcíny proti COVID-19 imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• vakcína BNT162 MeSH
• vakcíny proti COVID-19 MeSH

Immunosuppressed kidney transplant recipients are at risk for a variety of infectious complications and more than half of them suffered from this complication in the early post-transplant period. Despite the fact that the long term risk of serious infectious complications in the early postoperative period decreased, remain the infection the most frequent cause of morbidity in the first 6 months after transplant. It is important to realize that the clinical manifestations of infection in the compromised host are variable and often atypical. In the later period, infections that affect the kidney graft become clinically important, and some of them occur only in immunosuppressed patients. Here we will discuss polyomavirus nephropathy which represents the most important and most frequent viral disease of renal allografts.

• Klíčová slova
• polyomavirus nephropathy - kidney transplantation - infectious complications.,
• MeSH
• infekce onkogenními viry MeSH
• ledviny patologie   virologie   MeSH
• lidé MeSH
• polyomavirové infekce etiologie   MeSH
• pooperační komplikace patologie   virologie   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: To determine the incidence of infection with ganciclovir-resistant cytomegalovirus (CMV) in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. Clinical resistance or treatment failure was defined as persistent DNAemia or increasing viral load in peripheral blood after 2 weeks of virostatic treatment. The association between the treatment failure and viral resistance was analysed. The presence of ganciclovir-resistant CMV strains was confirmed by genotypic testing able to detect mutations conferring resistance. METHODS: In 2012 and 2014, 40 patients who underwent allogeneic HSCT for hematologic malignancies and were treated for human CMV reactivation/disease were followed up prospectively. In patients with treatment failure, CMV DNA was isolated and analysed by nucleotide sequence analysis of the UL 97 and UL 54 genes conferring resistance to the virostatic agent. RESULTS: The treatment failure occurred in seven patients, but ganciclovir resistance conferring mutations were only detected in two of them (mutations L595F and M460I in the UL 97 gene). Another mutation in the UL 97 gene (N510S) was found in a patient with recurrent CMV replication who needed to be retreated but did not meet the criteria for treatment failure. CONCLUSION: The low incidence of genetically confirmed ganciclovir-resistant CMV isolates in HSCT recipients with relatively common clinical treatment failure suggests that the mechanism underlying slower viral clearance is often other than mutations conferring ganciclovir resistance to the virus.

• MeSH
• antivirové látky terapeutické užití   MeSH
• cytomegalovirové infekce farmakoterapie   etiologie   virologie   MeSH
• Cytomegalovirus účinky léků   genetika   růst a vývoj   fyziologie   MeSH
• dospělí MeSH
• ganciklovir terapeutické užití   MeSH
• homologní transplantace škodlivé účinky   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• pooperační komplikace farmakoterapie   etiologie   virologie   MeSH
• terapie neúspěšná MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   MeSH
• virová léková rezistence * MeSH
• virová nálož účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• ganciklovir MeSH

UNLABELLED: Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. Because acute rejection is associated with inferior outcomes in lung transplantation, we have routinely employed antithymocyte globulin (ATG) or daclizumab as adjuncts to reduce the incidence of rejection episodes. METHODS: We performed a controlled clinical trial of the two therapies to evaluate differences in postoperative rejection, infection, bronchiolitis obliterans syndrome (BOS) and host survival. Twenty-five consecutive lung transplant patients received ATG (n = 12; group 1) or daclizumab (n = 13; group 2) as an induction agent. The groups showed similar demographics and immunosuppression protocols, differ only in induction agent. RESULTS: No differences were observed in the immediate postoperative outcomes, such as length of hospitalization, ICU stay, or time on ventilator. There were no significant differences in the number of episodes of acute rejection, freedom from BOS, or infections. Freedom from acute rejection was significantly greater with daclizumab than with ATG (P = .037). The 1-year survival for group 1 was 67% and for group 2, 77% (P = .584). CONCLUSIONS: Daclizumab constitutes a safe and effective form of induction immunosuppressive therapy. Using a two-dose administration schedule, daclizumab prolonged the time without acute rejection compared to ATG. The differences in the incidence of infectious complications, acute rejection, or BOS as well as the short-term or long-term results were not significantly different. The results of the study justify the further use of daclizumab as an induction agent in patients following lung transplantation.

• MeSH
• antilymfocytární sérum terapeutické užití   MeSH
• cytomegalovirové infekce epidemiologie   MeSH
• daklizumab MeSH
• dospělí MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• infekce epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• pooperační komplikace epidemiologie   virologie   MeSH
• rejekce štěpu epidemiologie   MeSH
• transplantace plic imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antilymfocytární sérum MeSH
• daklizumab MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G MeSH
• imunosupresiva MeSH
• monoklonální protilátky MeSH

AIMS: To compare the efficacy, costs and safety of oral ganciclovir and valacyclovir in the prophylaxis of cytomegalovirus (CMV) disease in renal transplant (RTx) recipients at high risk of CMV disease. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with either oral ganciclovir (3 g/day) or oral valacyclovir (8 g/day). A 3rd group received no prophylaxis. Forty-nine patients were considered to be at high risk of CMV disease due to D+R- serologic status, OKT3/ATG treatment and/or acute rejection within 12 months after RTx. Twenty-three high-risk patients were treated with ganciclovir (GAN group), 17 patients with valacyclovir (VAL group), and 9 patients received no prophylaxis (C group). RESULTS: No significant differences were found among the groups in their demographic characteristics, immunosuppressive protocols, D/R CMV serology, or CMV risk factors. The 12-month incidence of CMV disease was 89% in the C group compared with 9% in the GAN group and 6% in the VAL group (p < 0.001, GAN or VAL vs. C; p = 0.713, GAN vs. VAL). Treatment failure (death, graft loss, CMV disease or withdrawal from study) occurred in 17, 6, and 89% in the GAN, VAL, and C groups, respectively (p < 0.001, GAN or VAL vs. C; p = 0.285, GAN vs. VAL). The average CMV-associated costs per patient were EUR 3,161, 3,757, and 7,247 in the GAN, VAL, and C groups, respectively (p = 0.027). CONCLUSION: Valacyclovir and oral ganciclovir are equally effective in the prophylaxis of CMV disease in high-risk RTx patients. Both regimens are cost-effective and help reduce CMV-associated costs by nearly 50% compared with patients without prophylaxis.

• MeSH
• acyklovir aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• antivirové látky aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• cytomegalovirové infekce ekonomika   mortalita   prevence a kontrola   MeSH
• dospělí MeSH
• ganciklovir aplikace a dávkování   škodlivé účinky   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náklady na zdravotní péči MeSH
• pooperační komplikace ekonomika   prevence a kontrola   virologie   MeSH
• přežívání štěpu MeSH
• prospektivní studie MeSH
• rejekce štěpu farmakoterapie   MeSH
• rizikové faktory MeSH
• transplantace ledvin * mortalita   MeSH
• valaciclovir MeSH
• valin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• viremie ekonomika   mortalita   prevence a kontrola   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• ganciklovir MeSH
• imunosupresiva MeSH
• valaciclovir MeSH
• valin MeSH

Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus (CMV) disease after renal transplantation (RTx). Our study was designed to compare the efficacy, costs, and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx. A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir (1 g t.i.d., n=14, GAN group) or oral valacyclovir (2 g q.i.d., n=12, VAL group). A third group (C, n=12) received no prophylaxis. The patients were monitored by CMV-nested PCR in whole blood. No differences were found between the groups in their demographic characteristics, immunosuppressive protocols, or donor and recipient CMV serology. Thirty-six out of 38 (94.7%) recipients were CMV-seropositive. Over the 6-month post-RTx period, there were 13 episodes of CMV disease in eight (66.7%) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005, GAN vs C; P=0.001, VAL vs C). The incidence of CMV viremia was 30.8%, 50.0%, and 91.7% in the GAN, VAL, and C groups, respectively ( P=0.004, GAN vs C; P=0.07, VAL vs C; P=NS, GAN vs VAL). Treatment failure (death, graft loss, CMV disease, or withdrawal from study) occurred in 14.3%, 0% and 66.7% in the GAN, VAL, and C groups, respectively ( P=0.014, GAN vs C; P=0.001, VAL vs C; P=NS, GAN vs VAL). The average CMV-associated costs per patient (in 2001 euros) were 2,449+/-1,178, 2,485+/-581, and 4,259+/-4,616 in the GAN, VAL, and C groups, respectively. Ganciclovir and valacyclovir were well tolerated, with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia. In conclusion, oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx. Both are cost-effective and help reduce CMV-associated costs by some 40% compared with patients without prophylaxis.

• MeSH
• acyklovir aplikace a dávkování   analogy a deriváty   terapeutické užití   MeSH
• antivirové látky aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• cytomegalovirové infekce prevence a kontrola   MeSH
• dárci tkání MeSH
• dospělí MeSH
• ganciklovir aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mrtvola MeSH
• nemoci ledvin klasifikace   chirurgie   MeSH
• pooperační komplikace prevence a kontrola   virologie   MeSH
• prospektivní studie MeSH
• renální insuficience etiologie   chirurgie   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• valaciclovir MeSH
• valin aplikace a dávkování   analogy a deriváty   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• žijící dárci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• ganciklovir MeSH
• valaciclovir MeSH
• valin MeSH