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Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS-CoV-2 assays, defined by a ≥2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

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.

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.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.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.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.

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.

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna 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.

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna 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.

BackgroundThere 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.MethodsThis 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.ResultsFrom 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%).ConclusionsThe 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.

The Roche Cobas SARS-CoV-2 test recently received an Emergency Use Authorization from the U.S. Food and Drug Administration UA for pooling of up to six nasopharyngeal swab samples (NPS). We evaluated the 6-pool approach on both NPS and saliva samples using 564 samples (20 positive NPS and saliva samples each and 262 negative NPS and saliva samples each). The sensitivity of the Roche SARS-CoV-2 RNA test for pooled NPS samples was 100 % (95 %CI: 83.2-100 %) and the sensitivity for pooled saliva samples was 90 % (95 % CI: 68.3-98.8 %). Given the high throughput of the Roche Cobas 6800, pooling of 6 samples has the potential to significantly increase testing capacity without significant loss in sensitivity.

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

Access to rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for controlling the current global pandemic of coronavirus disease 2019. In this study, the use of oral rinses (ORs) and posterior oropharyngeal saliva as an alternative to swab collection methods from symptomatic and asymptomatic health care workers for the detection of SARS-CoV-2 RNA by RT-PCR was evaluated. For saliva samples, the overall agreement with oropharyngeal swabs was 93% (Ƙ = 0.84), with a sensitivity of 96.7% (95% CI, 83.3%–99.8%). The agreement between saliva and nasopharyngeal swabs was 97.7% (Ƙ = 0.93), with a sensitivity of 94.1% (95% CI, 73.0%–99.7%). ORs were compared with nasopharyngeal swabs only, with an overall agreement of 85.7% (Ƙ = 0.65), and a sensitivity of 63% (95% CI, 46.6%–77.8%). The agreement between a laboratory-developed test based on the CDC RT-PCR and two commercial assays, the Xpert Xpress SARS-CoV-2 and the Cobas SARS-CoV-2, was also evaluated. The overall agreement was >90%. Finally, SARS-CoV-2 RNA in saliva samples was shown to be stable, with no changes in viral loads over 24 hours at both room temperature and 4°C. Although the dilution of SARS-CoV-2 in ORs precluded its acceptability as a sample type, posterior oropharyngeal saliva was an acceptable alternative sample type for SARS-CoV-2 RNA detection.

Locally advanced rectal cancer has broadly been defined as T3, T4, or lymph node-positive disease. In the 1990s, adjuvant chemoradiation was considered the optimal management for locally advanced rectal cancer. However, the paradigm shifted when the German CAO/ARO/AIO-94 Rectal Cancer trial established neoadjuvant chemoradiation as the standard of care, based on reduced rates of toxicity and local recurrence, as well as higher rates of sphincter preservation compared with postoperative chemoradiation. Both short-course radiation and long-course chemoradiation are currently accepted methods for neoadjuvant treatment, with recent trials showing equivalence in outcomes. While surgery remains the cornerstone of treatment, there are data supporting the use of magnetic resonance imaging for risk stratification in rectal cancer and encouraging prospective data regarding nonoperative management. This review summarizes data on the evolution of treatment for locally advanced rectal cancer and discusses emerging evidence for nonoperative management.