Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease ...among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described.
Methods
We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients.
Results
Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range IQR 46–57), median time post-transplant was 5 years (IQR 2–10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 78%), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 adjusted odds ratio aOR 3.0, 95% confidence interval CI 1.7–5.5, P < .001, congestive heart failure aOR 3.2, 95% CI 1.4–7.0, P = .004, chronic lung disease aOR 2.5, 95% CI 1.2–5.2, P = .018, obesity aOR 1.9, 95% CI 1.0–3.4, P = .039) and presenting findings (lymphopenia aOR 1.9, 95% CI 1.1–3.5, P = .033, abnormal chest imaging aOR 2.9, 95% CI 1.1–7.5, P = .027) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality.
Conclusions
Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
In this analysis of 482 solid organ transplant recipients with coronavirus disease 2019 (COVID-19), the authors report 28-day mortality of 20.5% among inpatients, strongly associated with age and comorbidities, and conclude that this is comparable to rates observed in the general population.
A retrospective chart review was conducted on adult patients (greater than or equal to 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics ...between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the evaluation of community-acquired pneumonia, 30% to 60% of cases remain undiagnosed, despite extensive conventional microbiologic testing (CMT). Clinical metagenomics (CM) is an unbiased ...pathogen detection method that can increase diagnostic yield.
Does adding clinical metagenomics to conventional microbiologic testing improve the diagnostic yield for pneumonia in immunocompromised adults?
We performed a noninterventional prospective study of immunocompromised adults with pneumonia who underwent bronchoscopy and BAL over 2 years. CMT was performed per standard of care. A commercial CM test was performed on residual BAL fluid. Final microbiologic diagnoses were based on CMT vs CMT + CM. Final clinical diagnoses for CMT and CMT + CM were made based on laboratory results in conjunction with clinical and radiologic findings. Hypothetical impact of CMT + CM on management and antimicrobial stewardship was also assessed.
A total of 30 immunocompromised adult patients (31 episodes of pneumonia) were included. Final microbiologic diagnoses were made in 11 cases (35%) with the use of CMT and in 18 cases (58%) with the use of CMT + CM. Bacterial pneumonia was diagnosed in five cases (16%) by CMT and in 13 cases (42%) by CMT + CM; fungal pneumonia was diagnosed in six cases (19%) by CMT and in seven cases (23%) by CMT + CM, and viral pneumonia was diagnosed in two cases (6%) by CMT and in five cases (16%) by CMT + CM. The hypothetical impact of CMT + CM on management was deemed probable in one case, possible in eight cases, and unlikely in two cases, whereas the impact on antimicrobial stewardship was possible in 13 cases and unlikely in seven cases. Final clinical diagnoses were made in 20 of 31 cases (65%) based on CMT and in 23 of 31 cases (74%) based on CMT + CM.
CMT + CM increased diagnostic yield in immunocompromised adults with pneumonia from 35% to 58%, mostly by the detection of additional bacterial causes but was less useful for fungal pneumonia.
Under Our Very Eyes Koff, Alan; Malinis, Maricar; Delgado, Santiago ...
The New England journal of medicine,
03/2020, Volume:
382, Issue:
10
Journal Article, Conference Proceeding
Peer reviewed
A 64-year-old man with a history of ischemic cardiomyopathy presented to the emergency department in the summer with intermittent high fevers that began 7 weeks after he had undergone heart ...transplantation at that hospital. He also reported chills, nausea, and headaches.
Mycobacteria other than tuberculosis are important pathogens to consider in solid organ transplant recipients. Delay in recognition and treatment may incur significant morbidity and mortality. ...Management of mycobacteria other than tuberculosis requires a knowledge of treatment specific for each species and drug-drug interactions between antimicrobial and immunosuppressive drugs. Therapy in solid organ transplant can be prolonged and may require a reduction in immunosuppression to improve outcomes.
In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of ...transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift toward culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.
We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating ...therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0–3 L NC; severe, 4–6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution’s treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-
γ
, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (
p
= .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (
p
= .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ibrutinib is a small molecule tyrosine kinase inhibitor that blocks the activity of B cells and other immune effectors and is used in a variety of hematologic malignancies. There have been numerous ...reports of increased frequency of serious infections including invasive fungal infections (IFI) in patients on ibrutinib.
Demographic and clinical features of all patients receiving ibrutinib at a single tertiary care center were collected from electronic medical records. Univariate and multivariate statistical analyses were performed to find out the factors associated with infection.
A total of 244 patients received ibrutinib for hematologic malignancies, of which 44 (18.0%) experienced ≥ 1 serious infection including 5 (2.0%) with IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis), 39 (16.0%) with bacterial infections and 8 (3.3%) with viral infections. Ten patients (4.1%) experienced multiple infections or co-infections while on ibrutinib and 10 (4.1%) expired or were transferred to hospice as a result of infection. In multivariate analysis risk factors that were less common in uninfected versus infected patients included advanced age (73 years vs. 77 years), Eastern Cooperative Oncologic Grade (ECOG) performance score ≥ 2 (6.5% vs. 31.8%) and concurrent use of steroids (4.5% vs. 20.5%) or other cytotoxic agents (0% vs. 4.6%).
There was a high rate of serious infection but relatively few IFI in patients receiving ibrutinib. Most patients who developed serious infections while on ibrutinib had additional predisposing risk factors including concurrent use of steroids or other cytotoxic agents, advanced age and frailty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Direct visualization of
organisms, using Gomori methenamine silver (GMS) staining in bronchoalveolar lavage fluid (BAL), is a historical gold standard that has been widely used for the diagnosis of
...pneumonia (PJP). However, the stain may be less sensitive in human immunodeficiency virus (HIV)-negative immunocompromised patients owing to a lower burden of organisms.
To assess the sensitivity of the GMS stain on BAL fluid for the diagnosis of PJP in HIV-negative immunocompromised patients as compared to HIV-positive patients.
We conducted a retrospective review from 2012 to 2018 to identify immunocompromised patients (≥18 years old) who underwent bronchoscopy with BAL GMS staining for the diagnosis of PJP. To assess for sensitivity, we sought to identify BAL GMS-positive cases and BAL GMS-negative cases of PJP. The BAL GMS-negative cases were categorized into proven and probable PJP.
We identified 45 adult immunocompromised patients with proven and probable PJP, including 24 HIV-negative (11 BAL GMS-positive and 13 BAL GMS-negative) and 21 HIV-positive cases (all were BAL GMS-positive). The sensitivity of BAL GMS for the diagnosis of PJP in HIV-negative immunocompromised patients was 11 of 24 (46%) versus 21 of 21 (100%) in HIV-positive patients (CD4: median, 10 cells/mL; range, 3-300 cells/mL). Delayed or missed diagnoses were seen in 3 cases of BAL GMS-negative PJP. Re-examination of BAL GMS slides showed rare
cysts in 1 case.
BAL GMS has poor sensitivity for PJP in HIV-negative immunocompromised patients. Using BAL GMS as a sole method for PJP may result in missed or delayed diagnoses in this population.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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