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Abstract Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2

In the current study, we aimed (i) to evaluate sleep quality via wrist actigraphy monitoring of nonhospitalized and hospitalized post-COVID-19 condition (PCC) participants; (ii) to correlate actigraphy measures with subjective measures of sleep quality, such as the Pittsburgh Sleep Quality Index (PSQI); and (iii) to investigate whether total sleep time or sleep efficiency could affect PCC cognitive performance. We included 49 individuals with PCC from the NAUTILUS Project (NCT05307549 and NCT05307575) who were monitored for 1 week via actigraphy and who were also assessed with a comprehensive neuropsychological battery and the PSQI. We found that there were significant differences between nonhospitalized PCCs and hospitalized PCCs in the number of awakenings. We also found a correlation between the total sleep time of both measures (actigraphy and PSQI), but we did not observe correlations between objective and subjective parameters of latency and sleep efficiency. Regarding cognition and actigraphy measures, there was a trend of statistical significance in the performance of immediate visual memory, attention span and social cognition according to sleep efficiency. In conclusion, results indicate that although the PSQI provides clinically relevant indicators of sleep, there are divergent results between self-reported and objective sleep measures (actigraphy). Furthermore, we found a tendency toward statistical significance in cognitive performance in PCC participants according to their sleep efficiency which could indicate that is more important for cognitive function of post-COVID-19 patients than total sleep time.

Background: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. Methods: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. Results: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose + PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose + PAC vs. PAC alone p 0.37). Conclusions: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it. Resumen: Antecedentes: Faltan estudios que analicen alternativas no antibióticas para tratar las infecciones del tracto urinario (ITU) en los pacientes trasplantados renales. La D-Manosa, un azúcar simple, inhibe la adhesión bacteriana al urotelio, al igual que las Proantocianidinas; ambas moléculas podrían actuar como una estrategia sinérgica para prevenir las ITUs; pero su eficacia y seguridad aún no se han evaluado en la población trasplantada renal. Métodos: Este es un ensayo piloto prospectivo y doble ciego. Sesenta receptores de trasplante renal de novo fueron asignados al azar (1:1) para recibir una estrategia profiláctica basada en una formulación de liberación prolongada de 24 horas de D-Manosa más Proantocianidinas (PAC), frente a solo Proantocianidinas (PAC). Los suplementos se tomaron durante los primeros 3 meses después del trasplante renal y luego se realizó un seguimiento durante otros 3 meses. El objetivo principal del estudio fue determinar si la adición de D-Manosa a PAC reducía la incidencia de ITU y/o bacteriuria asintomática en los primeros 6 meses después del trasplante. Resultados: El 27% de los pacientes experimentó un episodio de ITU (cistitis o pielonefritis), mientras que la bacteriuria asintomática fue muy común (57%). Las incidencias según el tipo de ITU o bacteriuria asintomática fueron: 7% frente a 4% para episodio de cistitis (p 0.3), 4% frente a 5% para pielonefritis (p 0.5) y 17% frente a 14% para bacteriuria asintomática (p 0.4) en el grupo de manosa + PAC frente al grupo PAC, respectivamente. La bacteria más frecuente en ambos grupos fue Escherichia coli (28% de todos los episodios), sin embargo las ITU o bacteriuria asintomática debidas a E. coli no fueron diferentes según el grupo de estudio (30% frente a 23% para Manosa + PAC frente a PAC solo, p.0.37). Conclusiones: La terapia no antibiótica es una necesidad para prevenir las ITU después del trasplante renal; sin embargo, el uso de D-Manosa más PAC no parece ser capaz de prevenir las ITU en este grupo especial de pacientes.

ObjectiveIn the present study, we aimed to assess the cognition of post-COVID-19 condition (PCC) participants in relation to their subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI) and to analyse possible moderators of this effect, such as quality of life (European Quality of Life-5 Dimensions, EQ-5D), fatigue (Chadler Fatigue Questionnaire, CFQ), cognitive reserve (Cognitive Reserve Questionnaire, CRC), and subjective cognitive complaints (Memory Failures of Everyday Questionnaire, MFE-30).MethodsWe included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) who were assessed with a comprehensive neuropsychological battery and various questionnaires.ResultsWe found that PCC participants with poor sleep quality had a 4.3% greater risk of immediate verbal memory deficits than those with good sleep quality, as indicated by the greater odds ratio (OR) of 1.043 and confidence interval (CI) of 1.023–1.063. Additionally, their risk of immediate verbal memory disorders was multiplied by 2.4 when their EQ-5D score was low (OR 0.33; CI 0.145–0.748), and they had a lower risk of delayed visual memory deficits with a greater CRC (OR 0.963; CI 0.929–0.999). With respect to processing speed, PCC participants with poor sleep quality had a 6.7% greater risk of deficits as the MFE increased (OR 1.059; CI 1.024–1.096), and the risk of slowed processing speed tripled with a lower EQ-5D (OR 0.021; CI 0.003–0.141).ConclusionThese results indicate that poor subjective sleep quality is a potential trigger for cognitive deficits. Therapeutic strategies to maximize sleep quality could include reducing sleep disturbances and perhaps cognitive impairment in PCC individuals.

The study aimed to assess sleep quality in PCC patients and its predictors by analysing its relationship with emotional, cognitive and functional variables, as well as possible differences based on COVID-19 severity. We included 368 individuals with PCC and 123 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575). We assessed sleep quality (Pittsburgh Sleep Quality Index, PSQI), anxiety (Generalized Anxiety Disorder, GAD-7), depression (Patient Health Questionnaire, PHQ-9), global cognition (Montreal Cognitive Assessment, MoCA), everyday memory failures (Memory Failures of Everyday Questionnaire, MFE-30), fatigue (Chadler Fatigue Questionnaire, CFQ), quality of life (European Quality of Life-5 Dimensions, EQ-5D), and physical activity levels (International Physical Activity Questionnaire, IPAQ). 203 were nonhospitalized, 83 were hospitalized and 82 were admitted to the intensive care unit (ICU). We found statistically significant differences in the PSQI total score between the PCC and HC groups (p

One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants’ data, including 319 post-COVID and 109 healthy controls (18–65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent.Study registrationwww.ClinicalTrials.gov, identifiers NCT05307549 and NCT05307575.

Introduction: Although pentavalent antimonials are no longer considered the first-line therapy for visceral leishmaniasis in the developed world, they are still used in certain geographical areas and in refractory cases. These drugs have a great number of adverse effects; however, neurological toxicity has been rarely reported. Case report: We present a 56-year-old woman who required long-term treatment with antimonial drugs due to refractory visceral leishmaniasis and presented clinically with tremor of extremities, myoclonus, gait disturbances and epileptic seizures. The EEG showed increased beta rhythms and generalized epileptogenic activity. She had a slow but favorable response after the withdrawal of antimonials and the initiation of anticonvulsant therapy. Conclusion: Severe but reversible neurological toxicity is a rare adverse effect of prolonged antimonial treatment. More EEG record data are needed to support the suspicion of a possible increase of beta rhythms in this situation.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

ObjetivesThe aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance.MethodsUsing Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.ResultsAmong 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in ConclusionsNGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.

Late onset combined immunodeficiency (LOCID) is a rare variant of common variable immunodeficiency (CVID), typically affecting adult patients who present with opportunistic infections (OI) and/or low CD4+ T lymphocytes. Diagnostic delay is common due to the rareness of this entity, increasing morbidity and mortality. We report on a 66-year-old male who developed a severe gastrointestinal cytomegalovirus (CMV) infection, refractory to antiviral treatment and anti-cytomegalovirus specific human immunoglobulin administration, with a fatal outcome due to an undiagnosed LOCID.

Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance. [ABSTRACT FROM AUTHOR]

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

The role of contaminated preservation fluid in the development of infection after liver transplantation has not been fully elucidated. To assess the incidence and etiology of contaminated preservation fluid and determine its impact on the subsequent development of infection after liver transplantation, we prospectively studied 50 consecutive liver transplants, and cultured the following samples in each instance: preservation fluid (immediately before and at the end of the back-table procedure, and just before implantation), blood, and bile from the donor, and ascitic fluid from the recipient. When any culture was positive, blood cultures were obtained and targeted antimicrobial therapy was started. We found that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of liver transplantation per year), but only 28% (14/50) were contaminated by recognized pathogens. Blood and bile cultures from the donor were positive in 28% and 6% respectively, whereas ascitic fluid was positive in 22%. The most frequently isolated microorganisms were coagulase-negative staphylococci. In nine cases, the microorganisms isolated from the preservation fluid concurred with those grown from the donor blood cultures, and in one case, the isolate matched with the one obtained from bile culture. No liver transplant recipient developed an infection due to the transmission of an organism isolated from the preservation fluid. Our findings indicate that contamination of the preservation fluid is frequent in liver transplantation, and it is mainly caused by saprophytic skin flora. Transmission of infection is low, particularly among those recipients given targeted antimicrobial treatment for organisms isolated in the preservation fluid.