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1.
J Clin Virol ; 173: 105680, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38728796

RESUMO

BACKGROUND: Epstein-Barr Virus (EBV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Cobas EBV test (Roche Molecular, Pleasanton, CA) has recently been FDA-cleared for the monitoring of EBV viral loads in plasma samples of transplant patients. In this study, we compared the viral loads obtained by a laboratory-developed test (EBV LDT) using Altona Analyte specific reagents (ASR) to those obtained on the Cobas EBV test. METHODS: The analytical performance of the assay was established using the EBV verification panel from Exact Diagnostics and the EBV ATCC strain B95-8. The clinical evaluation was performed using 343 plasma samples initially tested on the EBV LDT. RESULTS: The analytical sensitivity (<18.8 IU/mL), precision (SD < 0.17 log) and linear range (35.0 IU/mL to 1E + 08 IU/mL) of the Cobas EBV assay established by the manufacturers were confirmed. The strength of the qualitative agreement was substantial between the cobas EBV and the EBV LDT (85.6 %; κ = 0.71) and almost perfect when discordant results were resolved (96.4 %; κ = 0.93). The quantitative agreement was moderate (82.9 %; κ = 0.53) with the viral load obtained on the Cobas EBV test being lower across the linear range of the two tests (mean log difference of 1.0). While the absolute values of the viral loads were markedly different, the overall trends observed in patients with multiple consecutive results were similar between the two tests. CONCLUSIONS: The Cobas EBV test provides an accurate and valid, in vitro diagnostic (IVD) option for monitoring of EBV viral loads in transplant patients and should provide an opportunity for increased standardization and commutability of tests results across laboratories.

2.
Eur J Clin Microbiol Infect Dis ; 43(3): 525-531, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38216845

RESUMO

BACKGROUND: Multiplex syndromic gastrointestinal panels (GIPCR) have streamlined the diagnosis of infectious diarrhea. Additionally, they have expanded the number of pathogens that can be routinely evaluated, allowing further understanding of the prevalence of enteric pathogens in various patient populations. The goal of this study was to investigate the prevalence and clinical presentation of astrovirus and sapovirus gastroenteritis in adult oncology patients as detected by the FilmArray GIPCR. METHODS: All GIPCR panel results from December 2017 to June 2021 were retrospectively reviewed to determine the prevalence of astrovirus and sapovirus in adult oncology patients. Medical records were also reviewed to obtain clinical information. Repeat GIPCR positivity and symptom duration were used to estimate prolonged viral shedding. RESULTS: A total of 18,014 panels were performed on samples collected from 9303 adults. Overall, astrovirus and sapovirus were detected in 0.35% (33/9303) and 0.45% (42/9303) GIPCRs respectively. At least one viral target was detected in 424 (4.4%) patients. Astrovirus accounted for 7.8% (33/424) and sapovirus 9.9% (42/424) of patients. Diarrhea was the most common symptom documented. A subset of transplant patients had protracted viral detection with a median of ~27 days (range 23-43 days) for astrovirus and 97 days (range 11-495) for sapovirus. No clusters or outbreaks were identified during the study period. CONCLUSION: In oncology patients with viral gastroenteritis, astrovirus and sapovirus were the causative agents in 18% of the cases. Both viruses were associated with mild disease. Prolonged diarrhea and viral shedding were observed in a few transplant patients.


Assuntos
Gastroenterite , Neoplasias , Norovirus , Sapovirus , Adulto , Humanos , Lactente , Sapovirus/genética , Prevalência , Estudos Retrospectivos , Norovirus/genética , Gastroenterite/diagnóstico , Diarreia/epidemiologia , Neoplasias/complicações , Fezes , Reação em Cadeia da Polimerase
3.
Transplant Cell Ther ; 30(1): 116.e1-116.e12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37806446

RESUMO

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell therapy (CAR-T) recipients who develop Coronavirus disease 2019 (COVID-19) can have decreased overall survival (OS), likely due to disease-inherent and therapy-related immunodeficiency. The availability of COVID-19-directed therapies and vaccines have improved COVID-19-related outcomes, but immunocompromised individuals remain vulnerable. Specifically, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections, including Omicron and its sublineages, particularly in HCT recipients, remain to be defined. The aim of this study was to compare the impact of SARS-CoV-2 Omicron infections in HCT/CAR-T recipients with outcomes previously reported for ancestral SARS-CoV-2 infections early in the pandemic (March to June 2020). This was a retrospective analysis of adult HCT/CAR-T recipients diagnosed with COVID-19 at Memorial Sloan Kettering Cancer Center between July 2021 and July 2022. We identified 353 patients (172 autologous HCT recipients [49%], 152 allogeneic HCT recipients [43%], and 29 CAR-T recipients [8%]), with a median time from HCT/CAR-T to SARS-CoV-2 infection of 1010 days (interquartile range, 300 to 2046 days). Forty-one patients (12%) were diagnosed with COVID-19 during the delta wave, and 312 patients (88%) were diagnosed during the Omicron wave. Risk factors associated with increased odds of COVID-19-related hospitalization were the presence of 2 or more comorbidities (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.4 to 10.7; P < .001), CAR-T therapy compared to allogeneic HCT (OR, 7.7; 95% CI, 3.0 to 20.0; P < .001), hypogammaglobulinemia (OR, 2.71; 95% CI, 1.06 to 6.40; P = .027), and age at COVID-19 diagnosis (OR, 1.03; 95% CI, 1.0 to 1.05; P = .04). In contrast, infection during the Omicron variant BA5/BA4-dominant period compared to variant BA1 (OR, .21; 95% CI, .03 to .73; P = .037) and more than 3 years from HCT/CAR-T therapy to COVID-19 diagnosis compared to early infection at <100 days (OR, .31; 95% CI, .12 to .79; P = .011) were associated with a decreased odds for hospitalization. The OS at 12 months from COVID-19 diagnosis was 89% (95% CI, 84% to 94%), with 6 of 26 deaths attributable to COVID-19. Patients with the ancestral strain of SAR-CoV-2 had a lower OS at 12 months, with 73% (95% CI, 62% to 84%) versus 89% (95% CI, 84% to 94%; P < .001) in the Omicron cohort. Specific COVID-19 treatment was administered in 62% of patients, and 84% were vaccinated with mRNA COVID-19 vaccines. Vaccinated patients had significantly better OS than unvaccinated patients (90% [95% CI, 86% to 95%] versus 82% [95% CI, 72% to 94%] at 12 months; P = .003). No significant difference in OS was observed in patients infected with the Omicron and those infected with the Delta variant (P = .4) or treated with specific COVID-19 treatments compared with those not treated (P = .2). We observed higher OS in HCT and CAR-T recipients infected with the Omicron variants compared to those infected with the ancestral strain of SARS-CoV2. The use of COVID-19 antivirals, mAbs, and vaccines might have contributed to the improved outcomes.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Adulto , Humanos , SARS-CoV-2/genética , COVID-19/terapia , Vacinas contra COVID-19/uso terapêutico , Tratamento Farmacológico da COVID-19 , Teste para COVID-19 , RNA Viral , Receptores de Antígenos Quiméricos/genética , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
4.
Cancer Immunol Res ; 12(3): 308-321, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38108398

RESUMO

Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.


Assuntos
Produtos Biológicos , Colite , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal/efeitos adversos , Estudos Prospectivos , Disbiose/terapia , Disbiose/etiologia , Resultado do Tratamento , Colite/terapia , Colite/complicações
6.
Mycopathologia ; 188(6): 863-871, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37365379

RESUMO

We performed a retrospective survey of non-Candida albicans candidemia in patients with cancer, including those with solid tumors and those with hematological malignancies as well as transplants patients both, solid-organ transplant recipients and hematopoietic stem cell transplant recipients. The study was performed at two healthcare centers in New York City and covered the years 2018-2022. A total of 292 patients (318 isolates) were included in the study. In order of frequency, C. glabrata (38%) was the most common species recovered, followed by C. parapsilosis (19.2%), C. tropicalis (12.6%), C. krusei (10.7%), C. lusitaniae (5.7%), and C. guilliermondii (4.4%). Micafungin was the most common antifungal treatment and 18.5% of patients were on antifungal prophylaxis. The 30-day crude mortality was 40%. 4.5% of patients had more than one non-albicans species detected. In conclusion, this study represents one of the largest surveys of non-albicans species in cancer and transplant patients and provides data on the current epidemiology of these Candida species in this patient population.


Assuntos
Candidemia , Neoplasias , Humanos , Antifúngicos/uso terapêutico , Transplantados , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Candida , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Candida glabrata , Candida parapsilosis , Candida tropicalis , Neoplasias/complicações , Neoplasias/tratamento farmacológico
7.
Haematologica ; 108(11): 3058-3067, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37345467

RESUMO

AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for pre-exposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or realworld experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 high-risk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher firsttime dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.


Assuntos
COVID-19 , Neoplasias Hematológicas , Profilaxia Pré-Exposição , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Infecções Irruptivas , Estudos Retrospectivos , Anticorpos Monoclonais , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico
9.
J Clin Virol ; 163: 105442, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37075690

RESUMO

BACKGROUND: In March 2020, nonpharmaceutical interventions (NPIs) including face coverings and social distancing were adopted to curb the spread of SARS-CoV-2. Over the course of the pandemic, adherence to these NPIs has varied and eventually became optional in most non healthcare settings. We investigated the impact of relaxation of NPI on the incidence of respiratory viruses other than SARS-CoV-2 at a tertiary cancer care hospital. METHODS: This was a retrospective cohort study of respiratory viral panel results performed at between 08/01/2014-07/31/2022. Only one viral target result per patient per year was included. Poisson regression models were used to compare 2019-2020, 2020-2021, and 2021-2022 incidence of respiratory viruses to those of 2014-2019. Interrupted time series analysis was performed using autoregressive integrated moving average models in order to compare expected and observed positivity rates. RESULTS: A large reduction in the odds of testing positive for a respiratory virus was observed for most respiratory viruses when comparing results from 2019 to 2020 group to the corresponding period in 2014-2019. Subsequent seasons showed ongoing reductions in the odds of testing positive while slowly increasing over time back toward pre-pandemic levels. A time interrupted series analysis showed that the monthly positivity rate for all respiratory pathogens were reduced after 03/01/2020, when compared to the expected values forecast, except for adenovirus. CONCLUSIONS: This study provides valuable data that could be used to guide public health practices and support the efficacy of NPIs in curtailing the spread of novel and endemic respiratory viruses.


Assuntos
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Incidência , Estudos Retrospectivos , SARS-CoV-2 , Neoplasias/epidemiologia , Neoplasias/prevenção & controle
10.
Clin Infect Dis ; 76(8): 1476-1482, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36445792

RESUMO

BACKGROUND: Sotrovimab is an anti-spike neutralization monoclonal antibody developed to reduce the risk of coronavirus disease 2019 (COVID-19) progression and advancement to hospitalization in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancy and the predictive factors of hospitalization. METHODS: We performed an observational study of 156 consecutive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19-related hospitalization(s) compared to those who did not. RESULTS: Among the 156 study patients, 17 (11%) were hospitalized, of whom 4 were readmitted for COVID-19-related complications; 3 deaths were attributed to COVID-19. Results from multivariable logistic regression show that significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted odds ratio [aOR], 5.59 [95% confidence interval {CI}, 1.73-18.12]; P = .004) and with relapse/refractory disease (aOR, 5.69 [95% CI, 1.69-19.16]; P = .005). Additionally, whole genome sequencing of severe acute respiratory syndrome coronavirus 2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treated with sotrovimab. CONCLUSIONS: While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in patients with hematologic malignancy when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , Recidiva Local de Neoplasia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Anticorpos Neutralizantes , Hospitalização
11.
Clin Microbiol Infect ; 28(12): 1624-1628, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35931373

RESUMO

OBJECTIVE: To describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance. METHODS: In a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness. RESULTS: Among the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic. DISCUSSION: Study demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Humanos , Cidade de Nova Iorque/epidemiologia , SARS-CoV-2/genética , Influenza Humana/prevenção & controle , RNA Mensageiro/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Retrospectivos , Pessoal de Saúde , Vacinas de mRNA
12.
Cancer Cell ; 40(7): 738-753.e5, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35679859

RESUMO

How immune dysregulation affects recovery from COVID-19 infection in patients with cancer remains unclear. We analyzed cellular and humoral immune responses in 103 patients with prior COVID-19 infection, more than 20% of whom had delayed viral clearance. Delayed clearance was associated with loss of antibodies to nucleocapsid and spike proteins with a compensatory increase in functional T cell responses. High-dimensional analysis of peripheral blood samples demonstrated increased CD8+ effector T cell differentiation and a broad but poorly converged COVID-specific T cell receptor (TCR) repertoire in patients with prolonged disease. Conversely, patients with a CD4+ dominant immunophenotype had a lower incidence of prolonged disease and exhibited a deep and highly select COVID-associated TCR repertoire, consistent with effective viral clearance and development of T cell memory. These results highlight the importance of B cells and CD4+ T cells in promoting durable SARS-CoV-2 clearance and the significance of coordinated cellular and humoral immunity for long-term disease control.


Assuntos
COVID-19 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Humanos , Imunidade Celular , Imunidade Humoral , Memória Imunológica , Receptores de Antígenos de Linfócitos T , SARS-CoV-2
13.
Artigo em Inglês | MEDLINE | ID: mdl-35586753

RESUMO

Identification of pathogens with pulmonary presentation in patients with hematologic malignancies may be challenging due to diagnostic difficulty related to the underlying malignancy and limitations of conventional microbiologic methods. Herein, we present a case series of three patients with pulmonary consolidations due to Legionella bozemanae necrotizing pneumonia, Pneumocystis jirovecii pneumonia, and disseminated Scedosporium infection, who were diagnosed by microbial cell-free DNA next-generation sequencing. We observed that this new sequencing modality was in agreement with gold-standard diagnostics, posing a potential solution to the problem of limited capability in diagnosing infections in hematological malignancy patients.

14.
Infect Control Hosp Epidemiol ; 43(10): 1413-1415, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34446121

RESUMO

In this retrospective study of 105 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-infected cancer patients with longitudinal nasopharyngeal sampling, the duration of viral shedding and time to attain cycle threshold >30 was longer in patients with hematologic malignancy than in those with solid tumors. These findings have important public health implications.


Assuntos
COVID-19 , Neoplasias , Humanos , Eliminação de Partículas Virais , SARS-CoV-2 , Estudos Retrospectivos , RNA Viral , Neoplasias/complicações
15.
Clin Infect Dis ; 74(9): 1579-1585, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34329418

RESUMO

BACKGROUND: There is limited information on the risk of hospital-acquired coronavirus disease 2019 (COVID-19) among high-risk hospitalized patients after exposure to an infected patient or healthcare worker (HCW) in a nonoutbreak setting. METHODS: This study was conducted at a tertiary care cancer center in New York City from 10 March 2020 until 28 February 2021. In early April 2020, the study institution implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing at admission and retesting every 3 days through the hospital stay. Contact tracing records were reviewed for all exposures to SARS-CoV-2 positive patients and HCWs. RESULTS: From 10 March 2020 to 28 February 2021, 11 348 unique patients who were SARS-CoV-2 polymerase chain reaction (PCR) negative at the time of admission underwent 31 662 postadmission tests during their hospitalization, and 112 tested positive (0.98%). Among these, 49 patients housed in semiprivate rooms during admission resulted in 74 close contacts and 14 secondary infections within 14 days, for an overall attack rate of 18.9%. Among those exposed to a roommate undergoing an aerosol-generating procedure (AGP), the attack rate was 35.7%. Whole genome sequencing (WGS) corroborated transmission in 6/8 evaluated pairs. In addition, three transmission events occurred in 214 patients with significant exposure to 105 COVID-19 positive healthcare workers (1.4%). CONCLUSIONS: The overall risk of hospital-acquired COVID-19 is low for hospitalized cancer patients, even during periods of high community prevalence. However, shared occupancy with an unrecognized case is associated with a high secondary attack rate in exposed roommates.


Assuntos
COVID-19 , Neoplasias , COVID-19/diagnóstico , COVID-19/epidemiologia , Busca de Comunicante , Atenção à Saúde , Pessoal de Saúde , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Neoplasias/epidemiologia , SARS-CoV-2
16.
Cancer Discov ; 12(1): 62-73, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753749

RESUMO

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/virologia , Infecção Persistente/imunologia , Infecção Persistente/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/imunologia , Linfócitos T/imunologia
17.
Access Microbiol ; 4(11): acmi000374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36644433

RESUMO

Introduction. The published literature characterizing the bacterial genus Acetobacter primarily explores the role of these organisms in the fermentation industry. Reports of human infections caused by Acetobacter species are rare and are primarily associated with immunocompromised patients. Case Presentation. A young patient with refractory acute myeloid leukaemia received a peripheral blood stem cell transplant at our institution. Both pre- and post-transplant courses were complicated by polymicrobial bloodstream infections. During this time a bacterium, later identified as Acetobacter tropicalis , was isolated from blood cultures. A. tropicalis was recovered in consecutive blood cultures for approximately 1 week; during this time the patient's condition deteriorated, ending in fatal cardiorespiratory failure. Conclusion. This case provides the first report of a human infection with A. tropicalis , although the significance of this finding in a complex patient is hard to establish. This illustrates how the routine implementation of molecular identification techniques by clinical microbiology laboratories will result in the reporting of more rare or novel micro-organisms involved in human infections.

18.
J Mol Diagn ; 23(12): 1741-1748, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34438100

RESUMO

Diagnosis and management of bacterial pneumonia still relies on bacterial culture and antimicrobial susceptibility testing. The Unyvero Lower Respiratory Tract panel (LRT) is a multiplex molecular assay that provides results within approximately 4.5 hours. This study evaluated the analytical performance of the LRT on bronchoalveolar lavage (BAL) fluids and bronchial washings (BW) in a cancer patient population and retrospectively determined clinical impact on therapy. Sensitivity and specificity of LRT on BAL and BW compared with bacterial culture and susceptibilities were calculated. Chart reviews were performed to determine whether antibiotic management would have changed based on the LRT results. A total of 113 BAL and 123 BW respiratory samples from 191 patients were included. The overall sensitivity and specificity were 91.7% (95% CI, 77.5%-98.3%) and 92.0% (95% CI, 87.3%-95.4%), respectively. Staphylococcus aureus was the most common target detected (n = 21) with 89.5% (95% CI, 66.8%-98.7%) sensitivity and 98.2% (95% CI, 95.4%-99.5%) specificity. Based on availability of LRT results, 4.8% of patients could have been de-escalated faster. The LRT demonstrated an overall high accuracy for the detection of common bacteria associated with pneumonia. In this cancer inpatient cohort, treatment adjustment based on LRT results would have occurred in a small number of cases. Larger studies are necessary to understand the real-world impact within specific high-risk populations.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasias/microbiologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bactérias/genética , Farmacorresistência Bacteriana/genética , Humanos , Pessoa de Meia-Idade , Neoplasias/complicações , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Sensibilidade e Especificidade , Centros de Atenção Terciária
19.
J Clin Microbiol ; 59(9): e0059821, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34232067

RESUMO

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sona Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). Serum and bronchoalveolar lavage (BAL) fluid samples received for GM EIA testing between March and August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient's medical records assessing for any evidence of a fungal infection. Five hundred thirty-three samples (85 BAL samples and 448 serum samples) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% confidence interval [CI], 72.2 to 100%) and 97.5% (95% CI, 95.5 to 98.4%), respectively. Fourteen of 24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable invasive aspergillosis (IA) was 100% (95% CI, 51.0 to 100%) and 87.5% (95% CI, 55.9 to 99.4%), with a specificity of 95.5% (95% CI, 92.3 to 97.2%) and 96.2% (95% CI, 93.4 to 97.7%), respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI, 1.28 to 69.9%) and 62.5% (95% CI, 30.6 to 86.3%), with a specificity of 98.2% (95% CI, 96.2 to 99.1%) and 99.2% (95% CI, 97.7 to 99.8%), respectively. The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.


Assuntos
Aspergilose Pulmonar Invasiva , Neoplasias , Aspergillus , Líquido da Lavagem Broncoalveolar , Galactose/análogos & derivados , Humanos , Mananas , Sensibilidade e Especificidade
20.
Nat Med ; 27(7): 1280-1289, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34017137

RESUMO

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias/imunologia , Idoso , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , COVID-19/complicações , COVID-19/mortalidade , Estudos de Coortes , Feminino , Neoplasias Hematológicas/complicações , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Imunofenotipagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Modelos de Riscos Proporcionais , Estudos Prospectivos , SARS-CoV-2 , Taxa de Sobrevida
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