Predictors of Coronavirus Disease 2019 Hospitalization After Sotrovimab in Patients With Hematologic Malignancy During the BA.1 Omicron Surge.

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.

Effectiveness of MRNA booster vaccine among healthcare workers in New York City during the Omicron surge, December 2021 to January 2022.

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.

Clinical and Genomic Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infections in mRNA Vaccinated Health Care Personnel in New York City.

BACKGROUND: Vaccine-induced clinical protection against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants is an evolving target. There are limited genomic level data on SARS CoV-2 breakthrough infections and vaccine effectiveness (VE) since the global spread of the B.1.617.2 (Delta) variant. METHODS: In a retrospective study from 1 November 2020 to 31 August 2021, divided as pre-Delta and Delta-dominant periods, laboratory-confirmed SARS CoV-2 infections among healthcare personnel (HCP) at a large tertiary cancer center in New York City were examined to compare the weekly infection rate-ratio in vaccinated, partially vaccinated, and unvaccinated HCP. We describe the clinical and genomic epidemiologic features of post-vaccine infections to assess for selection of variants of concern (VOC)/variants of interest (VOI) in the early post-vaccine period and impact of B.1.617.2 (Delta) variant domination on VE. RESULTS: Among 13658 HCP in our cohort, 12379 received at least 1 dose of a messenger RNA (mRNA) vaccine. In the pre-Delta period overall VE was 94.5%. Whole genome sequencing (WGS) of 369 isolates in the pre-Delta period did not reveal a clade bias for VOC/VOI specific to post-vaccine infections. VE in the Delta dominant phase was 75.6%. No hospitalizations occurred among vaccinated HCP in the entire study period, compared to 17 hospitalizations and 1 death among unvaccinated HCP. CONCLUSIONS: Findings show high VE among HCP in New York City in the pre-Delta phase, with moderate decline in VE post-Delta emergence. SARS CoV-2 clades were similarly distributed among vaccinated and unvaccinated infected HCP without apparent clustering during the pre-Delta period of diverse clade circulation. Strong vaccine protection against hospitalization was maintained through the entire study period.

Variable duration of viral shedding in cancer patients with coronavirus disease 2019 (COVID-19).

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.

Risk of Healthcare-Associated Transmission of Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Hospitalized Cancer Patients.

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.

Evaluation of a Commercial Multiplexed Molecular Lower Respiratory Panel at a Tertiary Care Cancer Center.

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.

Performance of the sona Aspergillus Galactomannan Lateral Flow Assay in a Cancer Patient Population.

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.

Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients.

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.

An Isothermal, Multiplex Amplification Assay for Detection and Genotyping of Human Papillomaviruses in Formalin-Fixed, Paraffin-Embedded Tissues.

Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. Analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples was performed. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens.

Effectiveness of ultraviolet disinfection in reducing hospital-acquired Clostridium difficile and vancomycin-resistant Enterococcus on a bone marrow transplant unit.

OBJECTIVE: To determine the effectiveness of ultraviolet (UV) environmental disinfection system on rates of hospital-acquired vancomycin-resistant enterococcus (VRE) and Clostridium difficile. DESIGN: Using active surveillance and an interrupted time-series design, hospital-acquired acquisition of VRE and C. difficile on a bone marrow transplant (BMT) unit were examined before and after implementation of terminal disinfection with UV on all rooms regardless of isolation status of patients. The main outcomes were hospital-based acquisition measured through (1) active surveillance: admission, weekly, and discharge screening for VRE and toxigenic C. difficile (TCD) and (2) clinical surveillance: incidence of VRE and CDI on the unit. SETTING: Bone marrow transplant unit at a tertiary-care cancer center.ParticipantsStem cell transplant (SCT) recipients.InterventionTerminal disinfection of all rooms with UV regardless of isolation status of patients. RESULTS: During the 20-month study period, 579 patients had 704 admissions to the BMT unit, and 2,160 surveillance tests were performed. No change in level or trend in the incidence of VRE (trend incidence rate ratio [IRR], 0.96; 95% confidence interval [CI], 0.81-1.14; level IRR, 1.34; 95% CI, 0.37-1.18) or C. difficile (trend IRR, 1.08; 95% CI, 0.89-1.31; level IRR, 0.51; 95% CI, 0.13-2.11) was observed after the intervention. CONCLUSIONS: Utilization of UV disinfection to supplement routine terminal cleaning of rooms was not effective in reducing hospital-acquired VRE and C. difficile among SCT recipients.

Evaluation of the Xpert MTB/RIF Performance on Tissues: Potential Impact on Airborne Infection Isolation at a Tertiary Cancer Care Center.

OBJECTIVES In this study, we sought to evaluate the performance of the Xpert MTB/RIF (Cepheid) assay for the detection of Mycobacterium tuberculosis (MTB) complex DNA on fresh and formalin-fixed, paraffin-embedded (FFPE) tissue specimens from oncology patients in an area with a low prevalence of tuberculosis. We also aimed to retrospectively assess the potential impact of Xpert MTB/RIF on the duration of airborne infection isolation (AII). SETTING A 473-bed, tertiary-care cancer center in New York City. DESIGN A total of 203 tissue samples (101 FFPE and 102 fresh) were tested using Xpert MTB/RIF, including 133 pulmonary tissue samples (65.5%) and 70 extrapulmonary tissue samples (34.5%). Acid-fast bacilli (AFB) culture was used as the diagnostic gold standard. The limit of detection (LOD) and reproducibility were also evaluated for both samples types using contrived specimens. The potential impact of the Xpert MTB PCR assay on tissue samples from AII patients on AII duration was retrospectively assessed. RESULTS Using the Xpert MTB/RIF for fresh tissue specimens, the sensitivity was 50% (95% CI, 1.3%-98.7%) and the specificity was 99% (95% CI, 94.5%-99.9%). For FFPE tissue specimens, the sensitivity was 100% (95% CI, 63.1%-100%) and the specificity was 98.3% (95% CI, 95.5%-100%. The LOD was 103 colony-forming units (CFU)/mL for both fresh and FFPE tissue specimens, and the Xpert MTB/RIF was 100% reproducible at concentrations 10 times that of the LOD. With an expected turnaround time of 24 hours, the Xpert MTB PCR could decrease the duration of AII from a median of 8 days to a median of 1 day. CONCLUSIONS The Xpert MTB/RIF assay offers a valid option for ruling out Mycobacterium tuberculosis complex (MTBC) on tissue samples from oncology patients and for minimizing AII resource utilization. Infect Control Hosp Epidemiol 2018;39:462-466.

Potential of real-time PCR threshold cycle (CT) to predict presence of free toxin and clinically relevant C. difficile infection (CDI) in patients with cancer.

OBJECTIVES: Clostridium difficile infection (CDI) is a toxin-mediated disease. Oncology patients are at increased risk for developing CDI. Diagnosis of CDI by PCR has led to misclassification of some C. difficile carriers as CDI cases. We determined if an optimized C. difficile PCR cycle threshold value (CT) could reliably predict presence of free toxin, and in turn improve the utility of PCR in detecting clinically relevant CDI in oncology patients. METHODS: 183 consecutive patients positive for C. difficile by the Xpert C. difficile were additionally tested using the cell culture cytotoxicity neutralization assay (CYT) and enzyme immunoassays (EIA). CT values at diagnosis and relevant clinical information were recorded. Receiver operating characteristic (ROC) curve was used to assess predictive validity and to find optimal CT for CYT positive cases. Severity of CDI was assessed by blinded charts review. RESULTS: Using CYT as the reference, ROC-derived Youden cut-off CT of 28.0 predicted 77% cytotoxin positive cases, and 91% and 100% of severe and complicated CDI episodes respectively. The median CT values for non-severe, severe, and complicated CDI episodes were 28.0, 24.5 and 22.5 respectively (p = 0.005). CONCLUSIONS: Lower CT value of the Xpert C. difficile PCR was associated with the presence of toxin and increased CDI severity. CT values may be beneficial in interpreting positive C. difficile PCR results.

Norovirus Loads in Stool Specimens of Cancer Patients with Norovirus Gastroenteritis.

In immunocompromised patients with norovirus (NoV) gastroenteritis, the relationship between fecal NoV load and clinical complications has not been examined. In this study, a validated real-time quantitative PCR assay was used to determine viral loads for NoV genogroup I and II (GI and GII) in NoV-positive stool specimens of cancer patients. A total of 234 specimens from 152 patients were positive for NoV, including 201 of GII and 33 of GI. Geometric mean of logarithmic copies per gram of stool (w/w) of NoV-GII were 9.03 ± 1.71 (means ± SD), which was significantly higher than that of NoV-GI [7.87 ± 1.49; odd ratio (OR), 3.22; 95% CI, 1.33-7.76; P = 0.009]. Among 152 patients with gastroenteritis, the fecal NoV geometric mean of logarithmic copy was correlated with mild (n = 85; 7.97 ± 1.55), moderate (n = 23; 9.09 ± 1.38), and severe (n = 44; 10.39 ± 0.91) episodes of severity by modified Vesikari scoring system, respectively. Multivariate analysis revealed that high level of NoV load was correlated with GII infections (OR, 4.13; 95% CI, 1.62-10.55; P = 0.003) and associated with development of severe clinical symptom (OR, 5.53; 95% CI, 2.00-7.24; P = 0.001) at the time of diagnosis. Infection with GII strains was more common than GI infection in cancer patients with viral gastroenteritis.

Limited diagnostic value of a multiplexed gastrointestinal pathogen panel for the detection of adenovirus infection in an oncology patient population.

BACKGROUND: Diagnosis of Adenovirus infections in transplant patients may be accomplished using either plasma or stool samples. IVD-cleared multiplexed gastrointestinal (GI) PCR panels offer an option for rapid testing of stool samples but most only target Adenovirus (HAdV) types F40/41. OBJECTIVES: Given the potential significance of a positive adenovirus test in an immunocompromised patient, we sought to determine the frequency of type 40/41 in our patient population and the utility of a readily available multiplexed, FDA-cleared GI Panel for the detection of adenovirus infections. STUDY DESIGN: A total of 215 specimens from immunocompromised patients mostly with hematologic malignancy or transplant recipients were evaluated including 107 plasma samples, 85 stool samples and 23 respiratory samples. Genotyping was performed successfully on 122 specimens. RESULTS: The most common type detected in all samples including stools was Adenovirus C/2. In a subset of patients with multiple specimen types tested, similar types were detected in all samples. CONCLUSIONS: Although Adenovirus F40/41 is the most common enteric type, Adenovirus C/2 was the most common type identified in stools and subsequently plasma samples of our patient population. Implementation of assays that have wide reactivity for most adenovirus types is essential for optimal diagnostic yield.