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BACKGROUND: Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization. METHODS: A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration. RESULTS: Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%). CONCLUSIONS: SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.
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COVID-19 , Trasplante de Órganos , Humanos , Autoinforme , COVID-19/epidemiología , SARS-CoV-2 , Calidad de Vida , Prueba de COVID-19 , Receptores de Trasplantes , Tos , Dolor , Trasplante de Órganos/efectos adversosRESUMEN
Background Pre-liver transplant (LT) sarcopenia is associated with poor survival. Methods exist for measuring body composition with use of CT scans; however, it is unclear which components best predict post-LT outcomes. Purpose To quantify the association between abdominal CT-based body composition measurements and post-LT mortality in a large North American cohort. Materials and Methods This was a retrospective cohort of adult first-time deceased-donor LT recipients from 2009 to 2018 who underwent pre-LT abdominal CT scans, including at the L3 vertebral level, at Johns Hopkins Hospital. Measurements included sarcopenia (skeletal muscle index [SMI] <50 in men and <39 in women), sarcopenic obesity, myosteatosis (skeletal muscle CT attenuation <41 mean HU for body mass index [BMI] <25 and <33 mean HU for BMI ≥25), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio. Covariates in the adjusted models were selected with use of least absolute shrinkage and selection operator regression with lambda chosen by means of 10-fold cross-validation. Cox proportional hazards models were used to quantify associations with post-LT mortality. Model discrimination was quantified using the Harrell C-statistic. Results A total of 454 recipients (median age, 57 years [IQR, 50-62 years]; 294 men) were evaluated. In the adjusted model, pre-LT sarcopenia was associated with a higher hazard ratio (HR) of post-LT mortality (HR, 1.6 [95% CI: 1.1, 2.4]; C-statistic, 0.64; P = .02). SMI was significantly negatively associated with survival after adjustment for covariates. There was no evidence that myosteatosis was associated with mortality (HR, 1.3 [95% CI: 0.86, 2.1]; C-statistic, 0.64; P = .21). There was no evidence that BMI (HR, 1.2 [95% CI: 0.95, 1.4]), VAT (HR, 1.0 [95% CI: 0.98, 1.1]), SAT (HR, 1.0 [95% CI: 0.97, 1.0]), and VAT/SAT ratio (HR, 1.1 [95% CI: 0.90, 1.4]) were associated with mortality (P = .15-.77). Conclusions Sarcopenia, as assessed on routine pre-liver transplant (LT) abdominal CT scans, was the only factor significantly associated with post-LT mortality. © RSNA, 2022 See also the editorial by Ruehm in this issue.
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Trasplante de Hígado , Sarcopenia , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Estudios Retrospectivos , Donadores Vivos , Composición Corporal , Músculo Esquelético , Tomografía Computarizada por Rayos X/métodosAsunto(s)
COVID-19 , Trasplante de Hígado , Anticuerpos , COVID-19/prevención & control , Humanos , Cinética , ARN Mensajero , SARS-CoV-2/genética , VacunaciónRESUMEN
BACKGROUND: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ . CONCLUSIONS: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.
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Vacunas contra la COVID-19 , COVID-19 , Receptores de Trasplantes , Anticuerpos Antivirales , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Aprendizaje Automático , Ácido Micofenólico , SARS-CoV-2 , Vacunas , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
INTRODUCTION: Loneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). METHODS: We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables. RESULTS: Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. CONCLUSION: Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.
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Enfermedad Hepática en Estado Terminal , Fragilidad , Trasplante de Hígado , Adulto , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Trasplante de Hígado/efectos adversos , Soledad , MasculinoRESUMEN
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 neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD 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.
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COVID-19 , Trasplante de Órganos , Ad26COVS1 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Receptores de Trasplantes , Vacunas Sintéticas , Vacunas de ARNmAsunto(s)
Formación de Anticuerpos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Vacunación/efectos adversosRESUMEN
Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.
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Disfunción Cognitiva/etiología , Fragilidad/etiología , Cirrosis Hepática/complicaciones , Anciano , Femenino , Humanos , Cirrosis Hepática/psicología , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Listas de Espera/mortalidadAsunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunidad Humoral/efectos de los fármacos , Enfermedades Musculoesqueléticas/inmunología , Ácido Micofenólico/administración & dosificación , Enfermedades Reumáticas/inmunología , Privación de Tratamiento , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Enfermedades Musculoesqueléticas/virología , Ácido Micofenólico/inmunología , Estudios Prospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/virología , SARS-CoV-2/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2-dose SARS-CoV-2 messenger RNA (mRNA) vaccination. METHODS: RMD patients (n = 1,377) who received 2-dose SARS-CoV-2 mRNA vaccination between December 16, 2020 and April 15, 2021 completed questionnaires detailing local and systemic reactions experienced within 7 days of each vaccine dose (dose 1 and dose 2), and 1 month after dose 2, detailing any flares of RMD. Associations between demographic/clinical characteristics and flares requiring treatment were evaluated using modified Poisson regression. RESULTS: Among the patients, 11% reported flares requiring treatment; there were no reports of severe flares. Flares were associated with prior SARS-CoV-2 infection (incidence rate ratio [IRR] 2.09, P = 0.02), flares in the 6 months preceding vaccination (IRR 2.36, P < 0.001), and the use of combination immunomodulatory therapy (IRR 1.95, P < 0.001). The most frequently reported local and systemic reactions included injection site pain (87% after dose 1, 86% after dose 2) and fatigue (60% after dose 1, 80% after dose 2). Reactogenicity increased after dose 2, particularly for systemic reactions. No allergic reactions or SARS-CoV-2 diagnoses were reported. CONCLUSION: Flares of underlying RMD following SARS-CoV-2 vaccination were uncommon. There were no reports of severe flares. Local and systemic reactions typically did not interfere with daily activity. These early safety data can help address vaccine hesitancy in RMD patients.
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Vacuna nCoV-2019 mRNA-1273/efectos adversos , Vacuna BNT162/efectos adversos , COVID-19/prevención & control , Enfermedades Musculoesqueléticas/inmunología , Enfermedades Reumáticas/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Adulto , Vacuna BNT162/administración & dosificación , COVID-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunología , Brote de los SíntomasAsunto(s)
Enfermedades Autoinmunes/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunidad Humoral/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Enfermedades Autoinmunes/virología , COVID-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021. RESULTS: Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted. CONCLUSIONS: Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.
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Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Anticuerpos Antivirales/sangre , Vacuna BNT162/administración & dosificación , COVID-19/prevención & control , Esquemas de Inmunización , Mieloma Múltiple/sangre , Vacuna nCoV-2019 mRNA-1273/efectos adversos , Anciano , Vacuna BNT162/efectos adversos , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Estudios Prospectivos , Vacilación a la Vacunación , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas de ARNm/administración & dosificación , Vacunas de ARNm/efectos adversosRESUMEN
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.