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1.
Am J Transplant ; 20(7): 1819-1825, 2020 07.
Artículo en Inglés | MEDLINE | ID: covidwho-2273562

RESUMEN

There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Neumonía Viral/complicaciones , Receptores de Trasplantes , Anciano , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Cuidados Críticos , Registros Electrónicos de Salud , Femenino , Hospitalización , Humanos , Huésped Inmunocomprometido , Terapia de Inmunosupresión/efectos adversos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/virología , Masculino , Persona de Mediana Edad , New York/epidemiología , Pandemias , Neumonía Viral/mortalidad , SARS-CoV-2
2.
Am J Transplant ; 22(8): 2089-2093, 2022 08.
Artículo en Inglés | MEDLINE | ID: covidwho-2256740

RESUMEN

The SARS-CoV-2 virus Omicron variant has now supplanted wild-type virus as the dominant circulating strain globally. Three doses of mRNA COVID-19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron-specific neutralization in transplant recipients after three-doses of mRNA-1273 vaccine. Neutralization was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney-pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA-1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log10 ID50 of 2.38 [range 1.34-3.57]). At 3 months, 8/51 (15.7%) were positive (median log10 ID50 [1.68; range 1.12-3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild-type, and Omicron vs. Delta (p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti-RBD response still had undetectable Omicron-specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients.


Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , COVID-19 , Receptores de Trasplantes , Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Humanos , Pruebas de Neutralización , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
3.
Am J Transplant ; 22(9): 2203-2216, 2022 09.
Artículo en Inglés | MEDLINE | ID: covidwho-2252450

RESUMEN

The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.


Asunto(s)
COVID-19 , Trasplante de Órganos , Obtención de Tejidos y Órganos , COVID-19/epidemiología , Prueba de COVID-19 , Supervivencia de Injerto , Humanos , Pandemias , Donantes de Tejidos
4.
Am J Transplant ; 23(2): 278-283, 2023 02.
Artículo en Inglés | MEDLINE | ID: covidwho-2259087

RESUMEN

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Receptores de Trasplantes , Anticuerpos Neutralizantes , Bioensayo , Infección Irruptiva , Anticuerpos Antivirales
5.
Am J Transplant ; 22(12): 3047-3052, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-2213461

RESUMEN

Pediatric solid organ transplant recipients (pSOTR) often demonstrate suboptimal vaccine responses and are not included in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy trials. This population has shown variable humoral immunity following SARS-CoV-2 vaccination, and no studies have assessed cell-mediated responses after SARS-CoV-2 vaccination in pSOTR. SARS-CoV-2-specific interferon-gamma release assay (IGRA), immunoglobulin G (IgG), and receptor-binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) blocking antibody (Ab) were measured in pSOTR aged 5-17 years after 2-3 doses of SARS-CoV-2 mRNA vaccine. In all, 33 subjects were included, with 25 tested after the second dose of mRNA vaccine (V2) and 21 tested after the third dose of mRNA vaccine (V3). Of the 19 subjects who had IgG testing after V3, 100.0% (19/19) had a positive IgG response. Of the 17 subjects who had IGRA testing after V3, 94.1% (16/17) had a positive IGRA response. RBD-ACE2 blocking antibody increased significantly from V2 to V3 (p = .007). Subjects <1 year from transplant demonstrated a significantly larger increase in RBD-ACE2 blocking Ab from V2 to V3 than did those >1 year from transplant (p = .05). SARS-CoV-2 vaccination induces humoral and cell-mediated responses in the majority of pSOTR, with improved quantitative humoral response after three doses.


Asunto(s)
COVID-19 , Trasplante de Órganos , Niño , Humanos , Vacunas contra la COVID-19 , Enzima Convertidora de Angiotensina 2 , ARN Mensajero , SARS-CoV-2 , COVID-19/prevención & control , Receptores de Trasplantes , Vacunación , Inmunoglobulina G , Anticuerpos Antivirales
6.
Am J Transplant ; 22(12): 2903-2911, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-2052209

RESUMEN

Emerging data support the safety of transplantation of extra-pulmonary organs from donors with SARS-CoV-2-detection. Our center offered kidney transplantation (KT) from deceased donors (DD) with SARS-CoV-2 with and without COVID-19 as a cause of death (CoV + COD and CoV+) to consenting candidates. No pre-emptive antiviral therapies were given. We retrospectively compared outcomes to contemporaneous DDKTs with negative SARS-CoV-2 testing (CoVneg). From February 1, 2021 to January 31, 2022, there were 220 adult KTs, including 115 (52%) from 35 CoV+ and 33 CoV + COD donors. Compared to CoVneg and CoV+, CoV + COD were more often DCD (100% vs. 40% and 46%, p < .01) with longer cold ischemia times (25.2 h vs. 22.9 h and 22.2 h, p = .02). At median follow-up of 5.7 months, recipients of CoV+, CoV + COD and CoVneg kidneys had similar rates of delayed graft function (10.3%, 21.8% and 21.9%, p = .16), rejection (5.1%, 0% and 8.5%, p = .07), graft failure (1.7%, 0% and 0%, p = .35), mortality (0.9%, 0% and 3.7%; p = .29), and COVID-19 diagnoses (13.6%, 7.1%, and 15.2%, p = .33). Though follow-up was shorter, CoV + COD was associated with lower but acceptable eGFR on multivariable analysis. KT from DDs at various stages of SARS-CoV-2 infection appears safe and successful. Extended follow-up is required to assess the impact of CoV + COD donors on longer term graft function.


Asunto(s)
COVID-19 , Trasplante de Riñón , Obtención de Tejidos y Órganos , Adulto , Humanos , Trasplante de Riñón/efectos adversos , SARS-CoV-2 , Supervivencia de Injerto , Estudios Retrospectivos , COVID-19/epidemiología , Prueba de COVID-19 , Estudios de Seguimiento , Factores de Riesgo , Donantes de Tejidos , Funcionamiento Retardado del Injerto/etiología
7.
Am J Transplant ; 22(12): 3137-3142, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-1973539

RESUMEN

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.130.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.452.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.731.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.267.92 for mTORi+tacrolimus; 2.34 5.5415.32 for mTORi-only; and 6.78 10.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.542.98 for MMF + mTORi; and 0.81 1.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.


Asunto(s)
COVID-19 , Trasplante de Riñón , Humanos , Tacrolimus , Ácido Micofenólico/uso terapéutico , Formación de Anticuerpos , Inhibidores mTOR , Vacunas contra la COVID-19 , SARS-CoV-2 , Rechazo de Injerto/prevención & control , COVID-19/prevención & control , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Receptores de Trasplantes , Serina-Treonina Quinasas TOR
8.
Am J Transplant ; 22(11): 2694-2696, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: covidwho-1932268

RESUMEN

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia. The second patient is a 22-year-old female with acute liver failure likely secondary to drug/toxin exposure. Both patients were treated with COVID-19-directed therapies and neither patient developed symptomatic disease. These cases demonstrate that LT can be safely performed in select patients with asymptomatic COVID-19 infection at the time of transplant.


Asunto(s)
COVID-19 , Trasplante de Hígado , Femenino , Humanos , Anciano , Adulto Joven , Adulto , Trasplante de Hígado/efectos adversos , SARS-CoV-2 , Pandemias , Listas de Espera
9.
Am J Transplant ; 22(11): 2637-2650, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: covidwho-1927553

RESUMEN

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8-12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4-13.8] vs. 7.4% [95% CI: 5.1-9.8], p = .009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9-39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5-6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1-34.6] vs. 48.5% [95% CI: 31.4-65.5], p = .011), as was mortality (1.8% [95% CI: 0.0-4.3] vs. 9.1% [95% CI: 0.0-18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.


Asunto(s)
COVID-19 , Trasplante de Riñón , Trasplante de Órganos , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Incidencia , Estudios Retrospectivos , Trasplante de Riñón/efectos adversos , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes , Vacunación , Hígado , Dinamarca/epidemiología
10.
Am J Transplant ; 22(11): 2627-2636, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: covidwho-1922817

RESUMEN

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization and death, and the effects of SARS-CoV-2 vaccines in solid organ transplant recipients (SOTRs) is still debated. We performed a nationwide, population-based, matched cohort study, including all Danish SOTRs (n = 5184) and a matched cohort from the general population (n = 41 472). Cox regression analyses were used to calculate incidence rate ratios (IRRs). SOTRs had a slightly increased risk of SARS-CoV-2 infection and were vaccinated earlier than the general population. The overall risk of hospital contact with COVID-19, severe COVID-19, need for assisted respiration, and hospitalization followed by death was substantially higher in SOTRs (IRR: 32.8 95%CI [29.0-37.0], 9.2 [6.7-12.7], 12.5 [7.6-20.8], 12.4 [7.9-12.7]). The risk of hospitalization and death after SARS-CoV-2 infection decreased substantially in SOTRs after the emergence of the Omicron variant (IRR: 0.45 [0.37-0.56], 0.17 [0.09-0.30]). Three vaccinations reduced the risk of SARS-CoV-2 infection only marginally compared to two vaccinations, but SOTRs with three vaccinations had a lower risk of death (IRR: 022 [0.16-0.35]). We conclude that SOTRs have a risk of SARS-CoV-2 infection comparable to the general population, but substantially increased the risk of hospitalization and death following SARS-CoV-2 infection. A third vaccination only reduces the risk of SARS-CoV2 infection marginally, but SOTRs vaccinated 3 times have reduced mortality.


Asunto(s)
COVID-19 , Trasplante de Órganos , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios de Cohortes , ARN Viral , Vacunas contra la COVID-19 , Trasplante de Órganos/efectos adversos , Dinamarca/epidemiología
11.
Am J Transplant ; 22(9): 2217-2227, 2022 09.
Artículo en Inglés | MEDLINE | ID: covidwho-1901570

RESUMEN

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.


Asunto(s)
COVID-19 , Trasplante de Hígado , Trasplante de Órganos , Obtención de Tejidos y Órganos , COVID-19/epidemiología , Prueba de COVID-19 , Humanos , Donadores Vivos , SARS-CoV-2 , Donantes de Tejidos , Estados Unidos/epidemiología
12.
Am J Transplant ; 22(11): 2675-2681, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: covidwho-1895939

RESUMEN

The cilgavimab-tixagevimab combination retains a partial in vitro neutralizing activity against the current SARS-CoV-2 variants of concern (omicron BA.1, BA.1.1, and BA.2). Here, we examined whether preexposure prophylaxis with cilgavimab-tixagevimab can effectively protect kidney transplant recipients (KTRs) against the omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of 150 mg tixagevimab and 150 mg cilgavimab, 39 (9.4%) developed COVID-19. With the exception of one case, all patients were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients (7.7%), respectively. Two KTRs died of COVID-19-related acute respiratory distress syndrome. SARS-CoV-2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n = 1). Viral neutralizing activity of the serum against the BA.1 variant was negative in the 12 tested patients, suggesting that this prophylactic strategy does not provide sufficient protection against this variant of concern. In summary, preexposure prophylaxis with cilgavimab-tixagevimab at the dose of 150 mg of each antibody does not adequately protect KTRs against omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.


Asunto(s)
COVID-19 , Trasplante de Riñón , Humanos , SARS-CoV-2 , Trasplante de Riñón/efectos adversos , Anticuerpos Neutralizantes , Anticuerpos Antivirales
14.
Am J Transplant ; 22(9): 2228-2236, 2022 09.
Artículo en Inglés | MEDLINE | ID: covidwho-1846164

RESUMEN

Limited data exists on the effectiveness of a third COVID-19 vaccine dose in solid organ transplant recipients. We conducted a population-based cohort study using linked healthcare databases from Ontario, Canada to answer this question. We included solid organ transplant recipients (n = 12,842) as of December 14, 2020, with follow-up until November 28, 2021. We used an extended Cox proportional hazards model with vaccination status, including BNT162b2, mRNA-1273, and ChAdOx1 vaccines, modeled as a time-dependent exposure. Individuals started in the unvaccinated category (reference) and could contribute person-time to first, second, and third doses. Over a median follow-up of 349 days, 12.7% (n = 1632) remained unvaccinated, 54.1% (n = 6953) received 3 doses, and 488 (3.8%) tested positive for SARS-CoV-2 (of which 260 [53.3%] had a clinically important outcome [i.e., hospitalization or death]). Adjusted vaccine effectiveness against infection was 31% (95% CI: 2, 51%), 46% (95% CI: 21, 63%), and 72% (95% CI: 43, 86%) for one, two, and three doses. Vaccine effectiveness against clinically important outcomes was 38% (95% CI: 4, 61%), 54% (95% CI: 23, 73%), and 67% (95% CI: 11, 87%). Vaccine effectiveness in solid organ transplant recipients is lower than the general population, however, vaccine effectiveness improved following a third dose.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Trasplante de Órganos , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Estudios de Cohortes , Humanos , Ontario/epidemiología , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Receptores de Trasplantes
15.
Am J Transplant ; 22(8): 2077-2082, 2022 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1745981

RESUMEN

Estimating the total coronavirus disease 2019 (COVID-19) mortality burden of solid organ transplant recipients (SOTRs), both directly through COVID-19 infection and indirectly through other impacts on the healthcare system and society, is critical for understanding the disease's impact on the SOTR population. Using SRTR data, we modeled expected mortality risk per month pre-COVID (January 2015-February 2020) for kidney/liver/heart/lung SOTRs, and compared monthly COVID-era deaths (March 2020-March 2021) to expected rates, overall and among subgroups. Deaths above expected rates were designated "excess deaths." Between March 2020 and March 2021, there were 3739/827/265/252 excess deaths among kidney/liver/heart/lung SOTRs, respectively, representing a 41.2%/27.4%/18.5%/15.0% increase above expected deaths. 93.0% of excess deaths occurred in patients age≥50. The observed:expected ratio was highest among Hispanic SOTRs (1.82) and lowest among White SOTRs (1.20); 56.0% of excess deaths occurred among Black or Hispanic SOTRs. 64.7% of excess deaths occurred among patients who had survived ≥5 years post-transplant. Excess deaths peaked in January 2021; geographic distribution of excess deaths broadly mirrored COVID-19 incidence. COVID-19 likely caused over 5000 excess deaths among SOTRs in the US in a 13-month period, representing 1 in 75 SOTRs and a substantial proportion of all deaths among SOTRs during this time. SOTRs will remain at elevated mortality risk until the COVID-19 pandemic can be controlled.


Asunto(s)
COVID-19 , Trasplante de Órganos , COVID-19/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Pandemias , Receptores de Trasplantes
16.
Am J Transplant ; 22(8): 2083-2088, 2022 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1741322

RESUMEN

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Lactamas , Leucina , Nitrilos , Prolina , Ritonavir , Receptores de Trasplantes , Adulto , Inhibidores de la Calcineurina/uso terapéutico , Ciclosporina/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Lactamas/uso terapéutico , Leucina/uso terapéutico , Nitrilos/uso terapéutico , Trasplante de Órganos , Prolina/uso terapéutico , Estudios Retrospectivos , Ritonavir/uso terapéutico , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico
18.
Am J Transplant ; 22(8): 2099-2103, 2022 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1685185

RESUMEN

Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.


Asunto(s)
COVID-19 , Trasplante de Riñón , Prueba de COVID-19 , Humanos , Trasplante de Riñón/efectos adversos , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rituximab/uso terapéutico , SARS-CoV-2/genética
20.
Am J Transplant ; 22(6): 1705-1713, 2022 06.
Artículo en Inglés | MEDLINE | ID: covidwho-1685183

RESUMEN

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Humanos , Donadores Vivos , SARS-CoV-2 , Encuestas y Cuestionarios , Receptores de Trasplantes , Estados Unidos/epidemiología
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