Third Time's a Charm - Covid-19 Vaccine Hope for Solid-Organ Transplant Recipients.
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ABSTRACT:
SUBMITTER: Williams WW
PROVIDER: S-EPMC8385552 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8262620 | biostudies-literature
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| S-EPMC8298284 | biostudies-literature
Project description:ImportanceVaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear.ObjectivesTo assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population.Design, setting, and participantsThis nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022.ExposuresSolid organ transplant.Main outcomes and measuresThe main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed.ResultsOf 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence.Conclusions and relevanceIn this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.
| S-EPMC10148200 | biostudies-literature
Project description:Solid organ transplant recipients were demonstrated to have reduced antibody response to the first and second doses of the COVID-19 mRNA vaccine. This review evaluated published data on the efficacy and safety of the third dose among solid organ transplant recipients. We performed a systematic search of PubMed, EMBASE, and Web of Science to retrieve studies evaluating the efficacy of the third dose of anti-SARS-CoV-2 vaccines in adult solid organ transplant recipients. Serologic response after the third vaccine was pooled using inverse variance and generalized linear mixed and random-effects models. Seven studies met our inclusion criteria. A total of 853 patients received the third dose. Except for one randomized controlled trial, all studies were retrospective in design. Following the third COVID-19 vaccine dose, antibody response occurred in 6.4-69.2% of patients. The pooled proportion of antibody response rate after the third vaccine was 50.3% (95% confidence interval (CI): 37.1-63.5, I2 = 90%). Five papers reported the safety profile. No severe adverse events were observed after the third vaccine dose. In conclusion, a third dose of the SARS-CoV-2 mRNA vaccine in solid organ transplant recipients is associated with improved immunogenicity and appears to be safe. Nevertheless, a significant portion of patients remain seronegative.
| S-EPMC8778934 | biostudies-literature
Project description:Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.
| S-EPMC8528082 | biostudies-literature
Project description:Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients.
| S-EPMC4261198 | biostudies-other
Project description:Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS-CoV-2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID-19, especially in high-risk patients. Herein, we describe our single-center experience of 93 SOT (50 kidney, 17 liver, 11 lung, nine heart, and six dual-organ) recipients with mild to moderate COVID-19 who were treated with bamlanivimab or casirivimab-imdevimab per emergency use authorization guidelines. Median age of recipients was 55 [(Interquartile range) 44-63] years, and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24-122) months and median time from the onset of COVID-19 symptoms to the infusion was 6 (IQR 4-7) days. All patients had a minimum 30 days of study follow-up. The 30-day hospitalization rate for COVID-19-directed therapy was 8.7%. Infusion-related adverse events were rare and generally mild. Biopsy-proven organ rejection occurred in two patients, and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID-19 who were eligible but did not receive MAB treatment had a higher 30-day hospitalization rate for COVID-19-directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age (Odds Ratio 0.49 [95% Confidence Interval 0.18-1.32], p = 0.16). Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID-19 in SOT recipients.
| S-EPMC8646855 | biostudies-literature
Project description:ImportanceSolid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19-related severity in this population are still insufficiently explored in the literature.ObjectiveTo examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19-related hospitalization in solid organ transplant recipients.Design, setting, and participantsUsing the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022.ExposuresImmunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities).Main outcomes and measuresThe main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately.ResultsOverall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients.Conclusions and relevanceThis study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19-related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.
| S-EPMC10630896 | biostudies-literature
Project description:GoalWe aimed to assess the incidence rate of coronavirus disease 2019 (COVID-19) in vaccinated versus unvaccinated solid organ transplant recipients (SOTR) at our center.MethodsWe abstracted the following clinical data from our transplant registry from 1/1/2021 to 6/2/2021: demographics, details of COVID-19 vaccination, incidence of COVID-19, and related mortality. We calculated incidence of symptomatic COVID-19 per 1000/person days at risk and incidence rate ratio (IRR).ResultsAmong 2151 SOTRs, 912 were fully vaccinated, and 1239 were controls (1151 unvaccinated, 88 partially vaccinated). Almost 70% of vaccinated subjects received the mRNA-1273 vaccine. There were 65 cases of COVID-19 that occurred during the study period - four occurred among fully vaccinated individuals and 61 among controls (including two in partially vaccinated individuals). Incidence rate for COVID-19 was 0.065 (95% CI 0.024-0.17) per 1000 person days in vaccinated versus 0.34 (95% CI 0.26-0.44) per 1000/person days in the control group; IRR was 0.19 (95% CI 0.049 -0.503, p < 0.005). There were no COVID-19 related deaths in the four breakthrough infections and two of 61 (3.3%) among controls.ConclusionWe demonstrate real world clinical effectiveness of COVID-19 vaccination in SOTRs with an almost 80% reduction in the incidence of symptomatic COVID-19 versus unvaccinated SOTRs during the same time.
| S-EPMC8420394 | biostudies-literature
Project description:BackgroundBamlanivimab and casirivimab-imdevimab are authorized for emergency use treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients at high risk for developing severe disease or hospitalization. Their safety and efficacy have not been specifically evaluated in solid organ transplant recipients.MethodsWe retrospectively reviewed solid organ transplant recipients who received monoclonal antibody infusion for COVID-19 at Mayo Clinic sites through January 23, 2021. Outcomes included emergency department visit, hospitalization, mortality, and allograft rejection.ResultsSeventy-three patients were treated, most commonly with bamlanivimab (75.3%). The median age was 59 years, 63% were male, and the median Charlson comorbidity index was 5. Transplant type included 41 kidney (56.2%), 13 liver (17.8%), 11 heart (15.1%), 4 kidney-pancreas (5.5%), 2 lung (2.7%), 1 heart-liver, and 1 pancreas. Eleven (15.1%) patients had an emergency department visit within 28 days of infusion, including 9 (12.3%) who were hospitalized for a median of 4 days. One patient required intensive care unit admission for a nonrespiratory complication. No patients required mechanical ventilation, died, or experienced rejection. Ten adverse events occurred, with 1 seeking medical evaluation. Hypertension was associated with hospital admission (P < .05), while other baseline characteristics were similar. The median time from symptom onset to antibody administration was 4 days in nonhospitalized patients compared with 6 days among hospitalized patients (P < .05).ConclusionsMonoclonal antibody treatment has favorable outcomes with minimal adverse effects in solid organ transplant recipients with mild to moderate COVID-19. Earlier administration of monoclonal antibody therapy appears to be more efficacious.
| S-EPMC8494079 | biostudies-literature