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The prolonged contagious period after viral infection in immunocompromised patients may affect how long precautions will be necessary to reduce further transmission. Replication-competent SARS-CoV-2 was detected for up to 61 days in patients who were immunocompromised by treatment for cancer.

Serum (1,3)-beta-D glucan (BDG) is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). BDG lacks specificity for PCP, and its clinical performance in high-risk cancer patients has not been fully assessed. Polymerase chain reaction (PCR) for PCP detection is highly sensitive, but cannot differentiate between colonization and infection. We evaluated the diagnostic performance of serum BDG in conjunction with PCP PCR on respiratory samples in patients with cancer and unexplained lung infiltrates. We performed a retrospective analysis of adult patients evaluated for PCP at our institution from 2012 to 2015, using serum BDG and PCP PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum BDG at different thresholds were evaluated using PCP PCR alone or in conjunction with clinical presentation in PCP PCR-positive patients. With PCP PCR alone as the reference method, BDG (≥80 pg/mL) had a sensitivity of 69.8%, specificity of 81.2%, PPV of 34.6%, and NPV of 95.2% for PCP. At ≥200 pg/mL in patients with a positive PCR and a compatible PCP clinical syndrome, BDG had a sensitivity of 70%, specificity of 100%, PPV of 100%, and NPV of 52.0% for PCP. Patients negative by both BDG and PCR were unlikely to have PCP. In patients with a compatible clinical syndrome for PCP, higher BDG values (>200 pg/mL) were consistently associated with clinically-significant PCP infections among PCP PCR-positive oncology patients.

The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi 1 , 2 . Although the composition of bacterial constituents has been linked to immune homeostasis and infectious susceptibility 3 – 7 , the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood 2 , 8 . Fungi represent a major cause of infectious morbidity and mortality in immunocompromised individuals, although the relationship of intestinal fungi (that is, the mycobiota) with fungal bloodstream infections remains undefined 9 . We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant. Patients with Candida bloodstream infection experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida spp. was associated with a substantial loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk of fungal bloodstream infections for pre-emptive therapeutic intervention. Expansion of pathogenic Candida species coupled with bacterial dysbiosis in the gut precedes Candida bloodstream infections in hematopoietic cell transplant recipients.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals 1 . Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer 2 , 3 , although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 4 . This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts. Analysis of a large, single-center cohort of patients with cancer who were infected with COVID-19 uncovers factors associated with disease severity and interactions with anti-cancer therapies

The FilmArray Respiratory Panel (RP) (BioFire™ Diagnostics, Inc., Salt Lake City, UT, USA) is the first multiplex molecular panel cleared by the US FDA for the detection of both bacterial and viral respiratory pathogens in nasopharygeal swabs. The FilmArray RP targets 20 pathogens including 17 viruses and subtypes and three bacteria, and is performed with minimal sample manipulation. The FilmArray RP has a fully automated sample-to-answer workflow with a turn-around-time of approximately 1 h. The reported sensitivity and specificity of the assay ranges from 80 to 100 and 100%, respectively, with the sensitivity for the adenovirus as low as 46%. A new version of the FilmArray RP assay (version 1.7) with improved sensitivity for the adenovirus was released in 2013. The performance characteristics and simplified workflow have allowed its implementation in a wide range of laboratories. The FilmArray RP has changed the diagnostic landscape and will have a significant impact on the care of patients with respiratory tract infection.

The Alpha (B.1.1.7) and Omicron (B.1.1.529, BA.1, BA.4 and BA.5) variants of concern (VOC) share several mutations in their spike gene, including mutations resulting in the deletion of two amino acids at position 69 and 70 (del 69–70) in the Spike protein. Del 69–70 causes failure to detect the S gene target on a widely used, commercial test, the TaqPath SARS-CoV-2 RT-PCR (Thermo Fisher). The S gene target failure (SGTF) signature has been used to preliminarily infer the presence of Alpha and Omicron VOC. We evaluated the accuracy of the SGTF signature in identifying these two variants through analysis of all positive SARS-CoV-2 samples tested on the TaqPath RT-PCR and sequenced by next generation sequencing between December 2020 to July 2022. 2324 samples were successfully sequenced including 914 SGTF positive samples. The sensitivity and specificity of the SGTF signature was 99.6% (95% CI 96.1–99.9%) and 98.6% (95% CI 99.2–99.8%) for the Alpha variant and 99.6% (95% CI 98.9–99.9%) and 99.8% (95% CI 99.4–99.9%) for the Omicron variant. At the peak of their corresponding wave, the positive predictive value of the SGTF was 98% for Alpha and 100% for Omicron. The accuracy of the SGTF signature was high, making this genomic signature a rapid and accurate proxy for identification of these variants in real-world laboratory settings.

BACKGROUNDUnderstanding outcomes and immunologic characteristics of cellular therapy recipients with SARS-CoV-2 is critical to performing these potentially life-saving therapies in the COVID-19 era. In this study of recipients of allogeneic (Allo) and autologous (Auto) hematopoietic cell transplant and CD19-directed chimeric antigen receptor T cell (CAR T) therapy at Memorial Sloan Kettering Cancer Center, we aimed to identify clinical variables associated with COVID-19 severity and assess lymphocyte populations.METHODSWe retrospectively investigated patients diagnosed between March 15, 2020, and May 7, 2020. In a subset of patients, lymphocyte immunophenotyping, quantitative real-time PCR from nasopharyngeal swabs, and SARS-CoV-2 antibody status were available.RESULTSWe identified 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days; IQR, 354-1611 days). Overall survival at 30 days was 78%. Clinical variables significantly associated with the composite endpoint of nonrebreather or higher oxygen requirement and death (n events = 25 of 77) included number of comorbidities (HR 5.41, P = 0.004), infiltrates (HR 3.08, P = 0.032), and neutropenia (HR 1.15, P = 0.04). Worsening graft-versus-host disease was not identified among Allo recipients. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Antibody responses were seen in a subset of patients.CONCLUSIONIn this series of Allo, Auto, and CAR T recipients, we report overall favorable clinical outcomes for patients with COVID-19 without active malignancy and provide preliminary insights into the lymphocyte populations that are key for the antiviral response and immune reconstitution.FUNDINGNIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748.

Background. The sensitivity of the MVista Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics) has been evaluated in disseminated histoplasmosis in patients with AIDS and in the \"epidemic\" form of acute pneumonia. Moreover, there has been no evaluation of the sensitivity of antigenemia detection in disseminated histoplasmosis after the implementation of methods to dissociate immune complexes and denature released antibodies. The goal of this study was to determine the sensitivity of the current antigen assay in different categories of histoplasmosis. Methods. Urine and serum specimens obtained from 218 patients with histoplasmosis and 229 control subjects, including 30 with blastomycosis, were tested. Results. Antigenuria was detected in 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplasmosis, 30.4% of 46 patients with subacute histoplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis. Among patients with disseminated cases, antigenuria was detected more often and at higher concentrations in immunocompromised patients and those with severe disease. Specificity was 99.0% for patients with nonfungal infections (n = 130) and in healthy subjects (n = 69), but cross-reactivity occurred in 90% of patients with blastomycosis. Conclusions. The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates that the global scientific community monitor, assess, and respond to the evolving coronavirus disease (COVID-19) pandemic. But the current reactive approach to emerging variants is ill-suited to address the quickly evolving and ever-changing pandemic. The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates that the global scientific community monitor, assess, and respond to the evolving coronavirus disease (COVID-19) pandemic. But the current reactive approach to emerging variants is ill-suited to address the quickly evolving and ever-changing pandemic. To tackle this challenge, investments in pathogen surveillance, systematic variant characterization, and data infrastructure and sharing across public and private sectors will be critical for planning proactive responses to emerging variants. Additionally, an emphasis on incorporating real-time variant identification in point-of-care diagnostics can help inform patient treatment. Active approaches to understand and identify “immunity gaps” can inform design of future vaccines, therapeutics, and diagnostics that will be more resistant to novel variants. Approaches where the scientific community actively plans for and anticipates changes to infectious diseases will result in a more resilient system, capable of adapting to evolving pathogens quickly and effectively.

Candida metapsilosis is a member of the Candida parapsilosis species complex, a group of opportunistic human pathogens. Of all the members of this complex, C. metapsilosis is the least virulent, and accounts for a small proportion of invasive Candida infections. Previous studies established that all C. metapsilosis isolates are hybrids, originating from a single hybridization event between two lineages, parent A and parent B. Here, we use MinION and Illumina sequencing to characterize a C. metapsilosis isolate that originated from a separate hybridization. One of the parents of the new isolate is very closely related to parent A. However, the other parent (parent C) is not the same as parent B. Unlike C. metapsilosis AB isolates, the C. metapsilosis AC isolate has not undergone introgression at the mating type-like locus. In addition, the A and C haplotypes are not fully collinear. The C. metapsilosis AC isolate has undergone loss of heterozygosity with a preference for haplotype A, indicating that this isolate is in the early stages of genome stabilization.