Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients.
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ABSTRACT:
SUBMITTER: Kamar N
PROVIDER: S-EPMC8262620 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesSolid organ transplant recipients (SOTR) receiving post-transplant immunosuppression show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines can overcome the reduced immune responsiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.MethodsWe analysed humoral immune responses against SARS-CoV-2 and its variants in 53 SOTR receiving SARS-CoV-2 vaccination.ResultsFollowing the initial vaccination series, 60.3% of SOTR showed no measurable neutralisation and only 18.9% demonstrated neutralising activity of > 90%. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titres against microbial recall antigens were higher. By contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titres against SARS-CoV-2 and its delta variants and fewer linear B-cell epitopes, indicating reduced B-cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titres and neutralising activity across alpha, beta and delta variants and to the induction of anti-SARS-CoV-2 CD4+ T cells in a subgroup of patients analysed. By contrast, we observed significantly lower antibody titres after the third dose with the omicron variant compared to the ancestral SARS-CoV-2 and the improvement in neutralising activity was much less pronounced than for all the other variants.ConclusionOnly a small subgroup of solid organ transplant recipients is able to generate functional antibodies after an initial vaccine series; however, an additional vaccine dose resulted in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron where antibody responses and neutralising activity remained suboptimal.
| S-EPMC9052011 | biostudies-literature
Project description: Not available
| S-EPMC8298284 | biostudies-literature
Project description: Not available
| S-EPMC8385552 | biostudies-literature
Project description:Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.
| S-EPMC9611839 | biostudies-literature
Project description: Not available
| S-EPMC8857776 | biostudies-literature
Project description:BackgroundThe study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients.MethodsWe conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls.ResultsAmong SOT recipients, VE was 29% (95% confidence interval [CI], -19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses.ConclusionsEffectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.
| S-EPMC9047160 | biostudies-literature
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