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We revisit the representation theory of the quantum double of the universal cover of the Lorentz group in 2+1 dimensions, motivated by its role as a deformed Poincar\'e symmetry and symmetry algebra in (2+1)-dimensional quantum gravity. We express the unitary irreducible representations in terms of covariant, infinite-component fields on curved momentum space satisfying algebraic spin and mass constraints. Adapting and applying the method of group Fourier transforms, we obtain covariant fields on (2+1)-dimensional Minkowski space which necessarily depend on an additional internal and circular dimension. The momentum space constraints turn into differential or exponentiated differential operators, and the group Fourier transform induces a star product on Minkowski space and the internal space which is essentially a version of Rieffel's deformation quantisation via convolution., Comment: 36 pages, 2 figures; minor corrections and additional references (version to appear in Letters in Mathematical Physics)

Background The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Methods We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. A linear mixed-effects regression analysis was performed. Results Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p < 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Flow chart A graph of the Cycle Threshold (Ct) values of the of Cepheid Xpert® Xpress SARS-CoV-2 assay measured on repeat screening of the 42 included patients. Graph of the fitted SOFA scores based on the Cycle Threshold values per patient. Conclusion Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. Disclosures All Authors: No reported disclosures

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2, as reflected by the Cycle threshold (Ct) value of the RT-PCR, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. Among 457 patients with COVID-19 pneumonia between 3/31/2020-4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2., The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. The two platforms demonstrate comparable performances; however, the run times for each assay are 3.5 h and 45 min, respectively. In search for a platform with a shorter turnaround time, we sought to evaluate the recently released Abbott ID Now COVID-19 assay, which is capable of producing positive results in as little as 5 min. We present here the results of comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID Now. Regardless of method of collection and sample type, Abbott ID Now COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

RationaleThe Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.ObjectivesWe explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.MethodsA retrospective cohort study among adult patients admitted to the hospital between March 31st to April 10th, 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) ≥35), intermediate (25MeasurementsA composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI).Main ResultsOf 457 patients with COVID-19 pneumonia from March 31st to April 10th, 2020, 316 met inclusion criteria. Included patients were followed for a median of 25days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (pConclusionsOur findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.

The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous scrutiny to which tests are normally subjected to prior to FDA approval. The need to identify the COVID-19 positive cases quickly and accurately has propelled the release of a variety of assays intended to meet the urgent demand. Several Nucleic Acid Amplification Tests (NAAT) platforms are currently available. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the result comparisons between Abbot ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in VTM as well as dry nasal swabs for the Abbott assay. Regardless of method of collection and sample type, Abbot ID NOW COVID-19 missed a third of the samples detected positive by Cepheid Xpert Xpress when using NP swabs in VTM and over 48% when using dry nasal swabs.

Background Limited data support the use of pneumococcal urinary antigen testing (PUAT) for patients admitted with community-acquired pneumonia (CAP) as a stewardship tool to curtail the use of broad-spectrum antimicrobials. At NYULH, CAP guidelines and admission order set were developed to standardize diagnostic testing, including PUAT. In this study we describe patients with positive versus negative PUAT and evaluate de-escalation and patients’ outcomes. Methods This was a retrospective study of adults admitted with diagnosis of CAP between January-December 2019 who had a PUAT performed. The primary outcome was incidence and timing of de-escalation of antimicrobials following PUAT result. Among patients with a positive PUAT we compared hospital length of stay (LOS), incidence of Clostridioides difficile infection (CDI), infection-related readmission within 30 days, and in-hospital mortality among those who were de-escalated versus those who were not de-escalated/required escalation. Results We evaluated 910 patients, of which 121 (13.3%) were PUAT positive. No difference in baseline characteristics, including severity of illness as represented by the Pneumonia Severity Index (97 [IQR 76-117] vs 89 [IQR 67-115], p=0.083) and Charlson Comorbidity Index, were observed between PUAT positive and negative groups. Time to PUAT testing occurred shortly after presentation to the hospital in both cohorts (16h [IQR 16-27] vs 13h [IQR 8-22], p=0.140). Initial de-escalation occurred in 97/117 (82.9%) and 629/775 (81.2%) of PUAT positive and negative patients, respectively (p = 0.749). Median time to de-escalation was shorter in the PUAT positive cohort (1 [IQR 0-2] vs 1 [IQR 1-2] day, p = 0.01). Among the PUAT positive group, hospital LOS stay was shorter in patients who were de-escalated compared to those who were not de-escalated/required escalation (6 days [IQR 4-10] vs 8 days [IQR 7-12], p=0.0005) with no difference in the incidence of CDI (2 [2.1%] vs 1 [3.7%], p=0.535), in-hospital mortality (4 [4.3%] vs 3 [11.1%], p=0.185), or 30-day infection-related readmission (2 [2.1%] vs 1 [3.7%], p=0.535). Conclusion PUAT positivity resulted in quicker time to targeted therapy for CAP. Among patients with a positive PUAT, initial de-escalation of antimicrobials did not lead to worse patient outcomes. Disclosures All Authors: No reported disclosures

Background The timely identification of a cluster is a critical requirement for infection prevention and control (IPC) departments because these events may represent transmission of pathogens within the health care setting. Given the issues with manual review of hospital infections, a surveillance system to detect clusters in health care settings must use automated data capture, validated statistical methods, and include all significant pathogens, antimicrobial susceptibility patterns, patient care locations, and health care teams. Methods We describe the use of SaTScan statistical software to identify clusters, WHONET software to manage microbiology laboratory data, and electronic health record data to create a comprehensive outbreak detection system in our hospital. We also evaluated the system using the Centers for Disease Control and Prevention's guidelines. Results During an 8-month surveillance time period, 168 clusters were detected, 45 of which met criteria for investigation, and 6 were considered transmission events. The system was felt to be flexible, timely, accepted by the department and hospital, useful, and sensitive, but it required significant resources and has a low positive predictive value. Conclusions WHONET-SaTScan is a useful addition to a robust IPC program. Although the resources required were significant, this prospective, real-time cluster detection surveillance system represents an improvement over historical methods. We detected several episodes of transmission which would have eluded us previously, and allowed us to focus infection prevention efforts and improve patient safety.

Background SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes. Methods We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) ≥35) intermediate (25< Ct< 35) and high (Ct ≤25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints. Results Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21–28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p< 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses. Flow Chart Prediction of Outcomes Based on Genomic Load Prediction of Outcomes Based on Genomic Load and Pneumonia Severity Index Conclusion High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic. Disclosures All Authors: No reported disclosures

Background Pneumonia is a leading cause of hospitalization and mortality. Due to the low yield of available diagnostic tests, ATS/IDSA pneumonia guidelines recommend a microbiologic work-up only for hospitalized patients with severe pneumonia. Methods From 5/2019 to 1/2020, we selected adult patients with clinical and radiographic findings highly suggestive of pneumonia. The BioFire® FilmArray® pneumonia panel was performed on sputum specimens that met quality microbiologic criteria and the results were compared to those of sputum cultures and other tests sent per standard of care. A limit of 105 copies/mL was used for positivity in semi-quantitative bacterial targets. The empiric antimicrobial regimen was reviewed to quantify the potential for antimicrobial optimization. Results Seventy patients were included in the analysis. Median age was 70 (IQR 53.5–81.75), and the majority (43 patients, 61.4%) were classified as Class IV and V using the pneumonia severity index, indicating severe cases of pneumonia. Sixty-nine patients completed at least a 5-day course for pneumonia and 14.3% died during their hospitalization. The fifteen patients (21.4%) that submitted a sputum culture before the initiation of antimicrobial therapy, had a trend towards a positive sputum culture (60% (9/15) vs 36.4% (20/55)) (p=0.09). The BioFire® FilmArray® pneumonia Panel increased the number of patients who received a microbiologic diagnosis from 29 (41%) to 59 (84.3%) (p< 0.001). The per isolate analysis revealed significantly more targets detected for Haemophilus influenzae (p=0.002) and Streptococcus pneumoniae (p=0.05). On review of empiric antimicrobial treatment, there was possibility for antimicrobial optimization in 80% of patients, including 9 cases of pathogens (4 MRSA, 3 Legionella pneumophila, 2 CTX-M gram-negative rods) where the pathogens were not covered and another 70 antimicrobials in 49 patients that could be stopped. Flow chart Bacterial Pathogens Detected in Standard of Care Alone Testing and with the Addition of Pneumonia Panel. Potential for Antimicrobial Optimization Using the Pneumonia Panel Conclusion Incorporation of the pneumonia panel in the diagnostic work-up of patients hospitalized with pneumonia substantially increased the rate of microbiologic diagnosis and had the potential to guide appropriate antimicrobial therapy. Future studies to quantify the effects on clinical outcomes and cost-effectiveness from tailored therapy are needed. Disclosures All Authors: No reported disclosures