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1.
Am J Transplant ; 24(7): 1303-1316, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38499087

RESUMO

Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) waves, including the impact of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, intensive care unit (ICU) admission, and 30-day and 1-year all-cause mortality. SARS-CoV-2 waves were categorized as Wildtype/Alpha/Delta (318 cases, 16.1%), Omicron BA.1 (268, 26.2%), Omicron BA.2 (268, 13.6%), Omicron BA.5 (561, 28.4%), Omicron BQ.1.1 (188, 9.5%), and Omicron XBB.1.5 (123, 6.2%). Severe COVID-19 rate was highest during the Wildtype/Alpha/Delta wave (44.6%), and lower in Omicron waves (5.7%-16.1%). Lung transplantation was associated with severe COVID-19 (OR: 4.62, 95% CI: 2.71-7.89), along with rituximab treatment (OR: 4.24, 95% CI: 1.04-17.3), long-term corticosteroid use (OR: 3.11, 95% CI: 1.46-6.62), older age (OR: 1.51, 95% CI: 1.30-1.76), chronic lung disease (OR: 2.11, 95% CI: 1.36-3.30), chronic kidney disease (OR: 2.18, 95% CI: 1.17-4.07), and diabetes (OR: 1.97, 95% CI: 1.37-2.83). Early treatment and ≥3 vaccine doses were associated with reduced severity (OR: 0.29, 95% CI: 0.19-0.46, and 0.35, 95% CI: 0.21-0.60, respectively). Tixagevimab/cilgavimab and bivalent boosters did not show a significant impact. The study concludes that COVID-19 severity decreased across different variants in SOTr. Lung transplantation was associated with worse outcomes and may benefit more from preventive and early therapeutic interventions.


Assuntos
COVID-19 , Transplante de Órgãos , SARS-CoV-2 , Transplantados , Humanos , COVID-19/epidemiologia , Transplante de Órgãos/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Transplantados/estatística & dados numéricos , Adulto , Idoso , Hospitalização/estatística & dados numéricos , Estudos Longitudinais , Unidades de Terapia Intensiva , Canadá/epidemiologia
2.
Am J Transplant ; 23(1): 78-83, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36148607

RESUMO

Solid organ transplant recipients (SOTr) remain at risk of severe COVID-19. Several previous early therapies are no longer effective against new circulating variants. We performed a prospective cohort study in outpatient adult SOTr during the omicron BA.2 wave (April-May 2022), to determine the effectiveness of 3 doses of remdesivir given within 7 days of symptoms onset. Patients were followed for at least 30 days. The primary outcome was hospitalization. Of 210 SOTr that had COVID-19, we included 192. The median age was 54.5 years and 61.5% were men. The most common transplants were kidney (41.7%), lung (19.3%), liver (18.8%), and heart (6.3%). Most patients (90.1%) had previously received ≥3 COVID-19 vaccine doses. Fifteen (7.8%) were hospitalized, 5(2.6%) required supplemental oxygen, 3(1.6%) ICU admission, and 2(1%) mechanical ventilation with 2(1%) deaths. Age, the number of comorbidities, prednisone chronic treatment, and lung transplant were risk factors for hospitalization. Early remdesivir significantly decreased the hospitalization rate: adjusted hazard ratio 0.12 (95% CI: 0.03-0.57). The adjusted number needed to treat to prevent one hospitalization was 15.2 (95% CI: 13.6-31.4). No patient that received early remdesivir needed ICU admission or died. In a cohort of SOTr with COVID-19 infection, administration of 3-dose early remdesivir independently reduced the disease severity.


Assuntos
COVID-19 , Transplante de Órgãos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/etiologia , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19 , Unidades de Terapia Intensiva , Pacientes Ambulatoriais , Estudos Prospectivos , SARS-CoV-2 , Transplantados
3.
Clin Infect Dis ; 75(12): 2193-2200, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-35445690

RESUMO

BACKGROUND: Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19) and vaccine breakthrough infections are common. We determined the effectiveness of ≥3 doses of mRNA vaccine and early monoclonal antibody therapy in reducing disease severity against the Omicron (B.1.1.529) variant. METHODS: Prospective cohort study of consecutive SOT recipients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to our transplant center who were followed for at least 30 days. The primary outcome was supplemental oxygen requirement. Effectiveness of sotrovimab and ≥3 vaccine doses was estimated using adjusted risk ratios (RR). RESULTS: Three hundred adult organ transplant recipients were included. Seventy-one patients (24.1%) were hospitalized, 44 (14.9%) required supplemental oxygen, 19 (6.5%) were admitted to the intensive care unit (ICU), 15 (5.1%) required mechanical ventilation (MV), and 13 (4.4%) died. On multivariate analysis, age and multiple comorbidities were risk factors for oxygen requirement. Both receipt of ≥3 vaccine doses prior to SARS-CoV-2 infection and receipt of sotrovimab in the first 7 days of symptom onset was associated with a reduction in the need for supplemental oxygen (RR 0.30 [95% confidence interval {CI}: .17 to .54] and RR 0.24 (95% CI: .1 to .59), respectively]. For sotrovimab, the number needed to treat (NNT) to prevent one patient requiring oxygen was 6.64 (95% CI: 4.56-13.66). Both sotrovimab use and having received ≥3 vaccine doses were also associated with a shorter hospitalization length of stay. CONCLUSIONS: In a cohort of SOT recipients with Omicron variant COVID-19 infection, prior receipt of ≥3 mRNA vaccine doses and early monoclonal antibody therapy were independently associated with significantly reduced disease severity.


Assuntos
COVID-19 , Transplante de Órgãos , Adulto , Humanos , SARS-CoV-2 , Estudos Prospectivos , Vacinação , Oxigênio , Transplantados
4.
Transplantation ; 108(5): 1249-1256, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38291585

RESUMO

BACKGROUND: Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients. METHODS: Using a large, prospective cohort of adult transplant patients with COVID-19, we identified patients with SARS-CoV-2 reinfections. We performed a 1:1 nearest neighbor propensity score matching to control potential confounders, including the COVID-19 variant. We compared outcomes including oxygen requirement, hospitalization, and intensive care unit admission within 30 d after diagnosis between patients with reinfection and those with the first episode of COVID-19. RESULTS: Between 2020 and 2023, 103 reinfections were identified in a cohort of 1869 transplant recipients infected with SARS-CoV-2 (incidence of 2.7% per year). These included 50 kidney (48.5%), 27 lung (26.2%), 7 heart (6.8%), 6 liver (5.8%), and 13 multiorgan (12.6%) transplants. The median age was 54.5 y (interquartile range [IQR], 40.5-65.5) and the median time from transplant to first infection was 6.6 y (IQR, 2.8-11.2). The time between the primary COVID-19 and reinfection was 326 d (IQR, 226-434). Three doses or more of SARS-CoV-2 vaccine are received by 87.4% of patients. After propensity score matching, reinfections were associated with significantly lower hospitalization (5.8% versus 19.4%; risk ratio, 0.3; 95% CI, 0.12-0.71) and oxygen requirement (3.9% versus 13.6%; risk ratio, 0.29; 95% CI, 0.10-0.84). In a within-patient analysis only in the reinfection group, the second infection was milder than the first (3.9% required oxygen versus 19.4%, P < 0.0001), and severe first COVID-19 was the only predictor of severe reinfection. CONCLUSIONS: Transplant recipients with COVID-19 reinfection present better outcomes than those with the first infection, providing clinical evidence for the development of cross-protective immunity.


Assuntos
COVID-19 , Transplante de Órgãos , Reinfecção , Transplantados , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização/estatística & dados numéricos , Transplante de Órgãos/efeitos adversos , Estudos Prospectivos , Reinfecção/epidemiologia , Fatores de Risco , Transplantados/estatística & dados numéricos , Resultado do Tratamento
5.
Nat Commun ; 13(1): 4489, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927279

RESUMO

Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4+ and CD8+ T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection.


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunidade Celular , Hospedeiro Imunocomprometido , SARS-CoV-2
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