Assessment of 4 Doses of SARS-CoV-2 Messenger RNA-Based Vaccine in Recipients of a Solid Organ Transplant.
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ABSTRACT:
SUBMITTER: Kamar N
PROVIDER: S-EPMC8613594 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials.MethodsUS transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression.ResultsWe studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44-69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P < 0.001), systemic reactions increased (49% D1 versus 69% D2, P < 0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 y = 0.850.900.94, P < 0.001) and D2 (aIRR per 10 y = 0.910.930.96, P < 0.001). Participants who experienced pain (aIRR = 1.111.662.47, P = 0.01) or redness (aIRR = 1.833.928.41, P < 0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post-D2.ConclusionsIn solid organ transplant recipients undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients.
| S-EPMC8487696 | biostudies-literature
Project description: Not available
| S-EPMC8262620 | biostudies-literature
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: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-EPMC9191559 | biostudies-literature
Project description: Not available
| S-EPMC8222879 | biostudies-literature
Project description: Not available
| S-EPMC8441706 | biostudies-literature
Project description:Detection of SARS-CoV-2 viral RNA by RT-PCR assays is the primary diagnostic test for COVID-19. Cycle threshold (CT ) values generated by some of these assays provide inversely proportional proxy measurements of viral load. The clinical implications of CT values are incompletely characterized, particularly in solid organ transplant (SOT) recipients. We conducted a retrospective chart review of 25 adult SOT recipients admitted to the Yale New Haven Health System between March 1 and May 15, 2020, analyzing 50 test results to investigate the clinical implications of SARS-CoV-2 CT values in this population. Initial CT values from upper respiratory tract samples were significantly higher in patients on tacrolimus, but were not associated with admission severity nor highest clinical acuity. Viral RNA was detected up to 38 days from symptom onset with a gradual increase in CT values over time. In five patients with serial testing, CT values <35.0 were detected >21 days after symptom onset in 4/5 and ≥27 days in 2/5, demonstrating prolonged RNA detection. These data describe SARS-CoV-2 viral dynamics in SOT patients and suggest that CT values may not be useful to predict COVID-19 severity in SOT patients. SARS-CoV-2 CT values may be more useful in informing infection prevention measures.
| S-EPMC7675520 | biostudies-literature
Project description:BackgroundThis is a descriptive study to characterize rates of SARS-CoV-2 infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in ped SOT recipients.MethodsWe queried OTTR for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 through June 30, 2021. Patients were tested by PCR: prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (i) acute infection vs. convalescence; (ii) acute infection vs. SOT recipients without infection (called healthy controls); (iii) LT vs. SB/MVT; (iii) positive vs. negative test result.ResultsOf 257 liver transplant (LT) recipients, 99 were tested: 6 were PCR positive,13 were antibody positive. Of 150 small bowel (SB)/ multi-visceral transplant (MVT) recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs. 10.0-years; p=0.017). We observed a rapid decline in viral load within 96-hours without a change in immunosuppression. Antibody lasted >8-months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 TEM cell frequency (p=0.04, p=0.03 respectively), decreased IFN-γ production from T-cells (2.8% vs.11.3% p=0.006), and decreased CD8 TEMRA frequency (4.56% vs.11.70% p=0.006).ConclusionEarly in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.
| S-EPMC9365074 | 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